Multiple Sclerosis Resource Centre
  • Home
  • About MS
  • MSRC Services
  • Get Involved
  • MS Research News
  • MSRC Groups
  • Useful Resources
  • Welcome To Josephs Court, MS Centre Of Excellence
  • Advertising
  • E-Newsletter
  • Contact Us
  • Cookie Policy
  • Investor in People
    You are here : Home » MS Research News » Drugs » Ampyra (Fampyra)

    Ampyra (Fampyra)

    A A A
    [Print this page]

    Share |


    Ampyra (Fampridine-SR) is a sustained-release tablet formulation of the drug fampridine (4-aminopyridine, or 4-AP). Data collected in laboratory studies found that fampridine can improve the communication between damaged nerves, which may result in increased neurological function.

    Ampyra® two-year safety data presented at ECTRIMS

    AmpyraAcorda Therapeutics, Inc. today announced safety data from more than 62,400 people with multiple sclerosis (MS) taking Ampyra (dalfampridine) Extended Release Tablets, 10 mg during the first two years of availability in the United States. The data showed that the safety profile of Ampyra is similar to that observed in clinical trials.

    This analysis was presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), being held in Lyon, France from October 10-13. Ampyra is known as prolonged-, modified, or sustained-release fampridine (Fampyra®) in some countries outside the United States.

    The analysis examined all post-marketing adverse events (AEs) that were reported to Acorda and the U.S. Food and Drug Administration (FDA) from March 2010 through March 2012. As is typical in post-marking data collection, there is a potential for underreporting of AEs. Key findings included:

    Among the 62,400 patients who were prescribed Ampyra during the first two years following FDA approval, 160 seizures were reported, or approximately 4.6 per 1000 patient-years of use. This rate is comparable to the rate of seizure seen in the overall MS population. Length of treatment prior to a seizure ranged from first dose to two years, with 20% of the seizures occurring within a week of starting treatment. Because of their disease, people with MS are at a higher risk of seizure than people who do not have MS.

    The most frequently reported AEs from March 2010 through March 2012 were dizziness, insomnia, balance disorder, headache, nausea, urinary tract infection, back pain, and asthenia. These are similar to the AEs most frequently reported during Ampyra clinical trials.

    "Ampyra has been available for over two years in the United States, providing us with safety data from real-world use by people with MS. These data showed that the safety profile of Ampyra in clinical practice is consistent with what was observed in clinical trials," said Enrique Carrazana, M.D., Acorda Therapeutics' Chief Medical Officer. "The data also indicate the rate of seizure has remained consistent over time, and is within the range that is expected in the overall MS population."

    This poster presentation was sponsored by Acorda Therapeutics, Inc. In markets outside of the United States, Ampyra is available as Fampyra. Fampyra is being developed and commercialized by Biogen Idec in these markets based on a licensing agreement with Acorda.

    Source: Daily Finance © Copyright 2012 AOL Inc (10/10/12)

    No added benefit proven for Fampridine in MS

    FampyraDrug manufacturer did not present evaluable study data on the appropriate comparator therapy

    Fampridine (trade name Fampyra®) has been approved in Germany since July 2011 for adult patients suffering from a higher grade walking disability (grades 4 to 7 on the EDSS disability status scale), as a result of multiple sclerosis (MS). The German Institute for Quality and Efficiency in Health Care (IQWiG) has assessed the added benefit of the drug pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG). According to the findings, there is no proof of added benefit, as the manufacturer's dossier contains no evaluable study data for the comparison between fampridine and the appropriate comparator therapy.

    G-BA specifies physiotherapy as the appropriate comparator therapy

    MS is a chronic incurable inflammatory disease, in which the patient's own immune system damages nerve tracts in the brain and spinal cord. In some patients, some muscles are in permanent spasm or are paralysed. If the disease is more advanced, patients may develop a walking disability.

    The Federal Joint Committee (G-BA) has specified physiotherapy as the appropriate comparator therapy for the benefit assessment. This treatment must fulfil the requirements of the German Guideline on Remedies (Heilmittelrichtlinie). In addition, the patients must receive optimised standard therapy for MS.

    Requirements for an indirect comparison not fulfilled

    There are no studies that directly compare fampridine with physiotherapy. Instead, the pharmaceutical company presented data on an indirect comparison. These data originate from studies in which fampridine was compared with a placebo or in which physiotherapy was compared with "no treatment".

    The legal ordinance on AMNOG explicitly specifies that it is possible to prove added benefit using indirect comparisons too. However, specific methodological conditions apply, which were not fulfilled by the manufacturer in the fampridine dossier.

    Marked differences in the grade of disability

    In addition, the studies on physiotherapy which the pharmaceutical company has evaluated cannot be used, as they also included patients with a markedly lower grade of disability (EDSS from 1.5) than in the studies on fampridine. Thus, the populations were not similar enough to allow a comparison between the results.

    Finally, the manufacturer does not discuss in the dossier whether the physiotherapy tested in these studies was in accordance with the criteria of the Guideline on Remedies and, if this is not the case, why these studies would nevertheless allow conclusions about the situation in Germany. Moreover, the manufacturer does not mention whether the patients actually received optimized MS standard therapy. However, these two points are conditions specified by the G-BA for the appropriate comparator therapy.

    Hence the manufacturer did not present evaluable studies on the appropriate comparator therapy for the assessment of the added benefit of fampridine, thereby also failing to present an evaluable indirect comparison. Thus there is no proof of added benefit of fampridine.

    G-BA decides on the extent of added benefit

    The dossier assessment is part of the overall procedure for early benefit assessment conducted by the G-BA. After publication of the manufacturer's dossier and its assessment by IQWiG, the G-BA initiates a formal commenting procedure which provides further information and can result in a change to the benefit assessment. The G-BA then decides on the extent of the added benefit, thus completing the early benefit assessment.

    Source: Medical News Today © MediLexicon International Ltd 2004-2012 (01/09/12)

    Top line results of 5 Mg dose Of Dalfampridine-ER for MS reported

    Ampyra (Fampyra)Acorda Therapeutics, Inc. announced top line results from a post-marketing commitment study assessing a 5mg dose of dalfampridine-ER to improve walking in people with multiple sclerosis, or MS. The study failed to confirm efficacy of the 5mg dose.

    According to the company, the study randomized 430 participants across three treatment arms - placebo, 5 mg or the currently marketed dose of 10 mg of dalfampridine-ER, twice daily. Baseline characteristics were measured at a single visit after randomization, following a qualifying screening visit. Study drug was then given for 4 weeks. Participants returned after 2 weeks on study drug for interim measurements (Visit 2) and again at 4 weeks (Visit 3).

    Acorda noted that the primary outcome was the change in walking speed (feet/second) on the Timed 25-Foot Walk test at Visit 3, measured at the time of peak plasma drug concentration, versus baseline. Improvements in the primary outcome for the 5 mg dose and the 10 mg dose at Visit 3 were not statistically significant compared to placebo, the company added.

    Source: RTT News Copyright © 2012 RTTNews (13/08/12)

    U.S. FDA warns about seizures with MS drug Ampyra

    AmpyraThe U.S. Food and Drug Administration has issued a warning to patients and physicians about the increased risk of seizures in multiple sclerosis patients taking the drug Ampyra.

    The drug was developed by Acorda Therapeutics Inc to improve walking ability in patients with multiple sclerosis. Biogen Idec Inc has rights to the drug in Europe where it is sold under the brand name Fampyra.

    The FDA said that based on reports, it recently evaluated seizure risk in MS patients taking Ampyra and noted that the majority of seizures happened within days to weeks after starting the recommended dose and occurred in patients with no history of seizures.

    Seizures are a known risk with Ampyra, the agency said, and the risk increases with higher blood levels of the drug. Since Ampyra is eliminated from the kidneys, patients with kidney impairment may develop higher blood levels of the drug, thus increasing their seizure risk, the FDA said.

    As a result, the agency is updating the prescribing information for physicians, making clear that a patient's kidney function should be checked before starting Ampyra. Patients should be monitored at least once a year while the treatment continues.

    In addition, patients who miss a dose should not take extra doses as an extra dose can increase seizure risk, the agency said.

    The drug was approved in the United States in January 2010. Biogen received conditional approval for drug in Europe last July. Conditional approval is granted to drugs in which the benefit is seen to outweigh the risk but where additional information is needed to confirm that view.

    As part of the conditions of approval, regulators recommended Biogen carry out an additional study to discover more about the drug's benefits and safety over the long term.

    Source: EmpowHER Copyright © 2012 HW, LLC (24/07/12)

    Acorda says MS drug, Ampyra benefits lasted up to 5 years

    AmpyraAcorda Therapeutics Inc. said Wednesday that clinical study data shows its multiple sclerosis drug Ampyra continued to help patients for up to five years.

    Ampyra is used to improve the walking speed in MS patients. The company said Wednesday that the benefits of Ampyra that were observed in clinical trials continued for as much as five years in extension studies. The report was based in 483 patients who participated in a late-stage clinical trial of the drug and agreed to join the extension study.

    Acorda said patient's walking speed was measured three times in the first six months of the extension study and once every six months after that. The company presented data from the study at the American Academy of Neurology Meeting in New Orleans.

    Acorda Therapeutics reported $210.5 million in Ampyra sales in 2011, and it expects $255 million to $275 million in revenue in 2012.

    Source: Bloomberg Business Exchange COPYRIGHT 2012 BLOOMBERG L.P (26/04/12)

    Oral MS drug Fampyra™ now available in Canada to improve walking

    FampyraBiogen Idec Canada announces that Fampyra (fampridine sustained release tablets or fampridine SR) is now available for prescription for patients living with multiple sclerosis (MS) in Canada.

    Health Canada approved Fampyra on February 10, 2012 for the symptomatic improvement of walking in adult MS patients with walking disability (EDSS 3.5-7).

    Walking impairment is one of the most common and disruptive consequences of MS and Fampyra is the first approved treatment that addresses this unmet medical need. In clinical trials, it demonstrated efficacy in people with all types of MS.

    Patients with MS consistently rate walking as the most important function they want to maintain, regardless of what stage they are in their disease. Walking impairment is directly associated with loss of independence, restrictions on a patient's ability to work and a reduction in overall levels of household income. In fact, a research survey shows that 88 per cent of sampled Canadians living with MS report that difficulty walking affects their overall mobility.

    "For patients with MS, one of the greatest areas affected in their lives is walking. Until fampridine SR (Fampyra), there have been no pharmacologic agents shown to directly improve walking function in persons with multiple sclerosis," said Dr. Christine Short, Associate Professor, Department of Medicine, Division of Physical Medicine and Rehabilitation, Dalhousie University, Halifax, NS. "As a clinician who manages persons with multiple sclerosis, the approval of this treatment in Canada represents a real breakthrough in our battle to help individuals maintain independence and quality of life in the face of a progressive neurologic disease."

    MS is an unpredictable, often debilitating disease of the central nervous system that attacks the protective covering, or myelin, of the brain and spinal cord, causing inflammation and damage. When this occurs, the normal flow of nerve impulses along nerve fibres, or axons, becomes disrupted. Studies show that Fampyra can increase conduction along damaged nerves and enable signals to pass down the nerve more normally, which may result in improved walking for adult MS patients.

    Clinical Data Demonstrates Efficacy The approval of Fampyra for the improvement of walking in adult patients with MS was based on the results of two Phase III clinical trials: MS-F203 and MS-F204.

    The primary endpoint was the responder rate based on walking speed as measured by the Timed 25-Foot Walk (T25FW). A significantly greater proportion of patients taking Fampyra had consistent improvement in walking speed when compared to placebo (ms-f203:34.8 per cent to 8.3 per cent)(and ms-f204:42.9 per cent to 9.3 per cent). In patients who responded to therapy in the two studies, MS-F203 and MS-F204, Fampyra increased their walking speed on average by 26.3 per cent to 5.3 per cent on placebo, and 25.3 per cent to 7.8 per cent, respectively.

    "Seeing the effects of these results will have an important impact on patients," said Dr. Brad Stewart, Neurologist and Assistant Clinical Professor, University of Alberta, Edmonton, Alberta. "As mobility impairment in MS is progressive, Fampyra is a welcomed, new treatment to address this unmet need in the management of walking difficulties."

    Important Safety Information The use of Fampyra is contraindicated in patients with a known hypersensitivity to fampridine or any ingredient in the formulation; currently on treatment with other forms of 4-aminopyridine, dalfampridine or fampridine; with a history of mild, moderate or severe renal impairment; or with a history of seizure or medically assessed as at high risk of seizure.

    Fampyra should only be used under the supervision of a clinician experienced in the treatment of MS and familiar with the safety and efficacy of Fampyra. The recommended dose of one sustained release 10 mg tablet twice daily, taken 12 hours apart, should not be exceeded.

    The most common adverse events with incidence greater than or equal to two per cent and at a rate greater than the placebo rate for Fampyra were urinary tract infection, insomnia, dizziness, headache, nausea, asthenia, back pain, balance disorder, paraesthesia, nasopharyngitis and constipation.

    Source: Market Watch Copyright © 2012 MarketWatch, Inc (11/04/12)

    Interactive website for Ampyra® (Dalfampridine) MS users launched

    AmpyraAcorda Therapeutics, Inc. has announced the launch of a new interactive patient website called Ampyra Journeys. The site is the first-ever stand-alone patient site to focus on walking problems associated with multiple sclerosis (MS). Ampyra (dalfampridine) is an oral medication approved by the FDA as a treatment to improve walking in patients with multiple sclerosis. This was demonstrated by an increase in walking speed.

    The Ampyra Journeys website features true stories of people living with MS who have experienced walking problems and who took action to get treatment. Their stories explore the impact that walking problems can have for people living with MS, and how treatment that leads to improvements in walking can help people to regain the ability to perform many daily tasks. Prominent MS patient advocate, motivational speaker and entertainer Kristie Salerno Kent is among the patients who share their personal stories on www.AmpyraJourneys.com.

    “I have met so many people living with MS who did not seek help when they started to experience walking problems. The important news is that treatment is available, and so I am very excited to be involved with Ampyra Journeys. This new website is a vital resource that can help anyone living with MS to learn about, and to do something about, MS-related walking problems,” said Ms. Salerno Kent.

    Walking problems are a significant concern for people living with MS. According to a 2011 Harris Interactive Survey, approximately 70% of people with MS who experience difficulty walking identify this issue as the biggest challenge associated with MS.

    Visitors to the website can also download “Let’s Talk About Walking and MS,” a guide with tips on how to talk about walking problems with a healthcare provider.

    “Acorda Therapeutics developed Ampyra to help patients with walking problems, one of the most challenging and common symptoms of MS. Now we are very pleased to present Ampyra Journeys, to help more people get the support they need to get treatment. It's our hope that this site will educate and inspire people to seek help for their MS-related walking problems,” said Ron Cohen, MD, president and CEO of Acorda Therapeutics.

    Source: EON ©2012 Business Wire (03/04/12)

    Fampyra launched in the UK to aid MS walking

    FampyraFampyra (fampridine) is indicated for use in multiple sclerosis to improve walking in patients who have a walking disability (EDSS 4-7).

    Pharmacology

    Fampridine is a potassium channel blocker. It prolongs channel repolarisation which enhances action potential formation in demyelinated axons, leading to improved neurological function.1

    Clinical Studies

    The efficacy of fampridine to improve walking was established in two double-blind studies in which patients with multiple sclerosis were randomised to receive prolonged-release fampridine 10mg twice daily or placebo. Completion of a timed 25-foot walk was used as the primary efficacy endpoint in both studies. Patients who showed a faster walking speed on at least 3 out of 4 occasions, in comparison to their walking speed before treatment, were considered to have responded to treatment.1,2

    In one study (n=296), 34.8% of patients taking fampridine responded to the treatment, with an average increase in walking speed of 26.3% vs 5.3% on placebo (p<0.001). The other study (n=237) showed similar results with 42.9% responding to treatment and an increase in walking speed of 25.3% vs 7.8% (p<0.001).1-3

    Treatment should be initiated and supervised by a specialist doctor experienced in the management of multiple sclerosis. Treatment should be limited to two weeks by which time any clinical benefits should have been identified. A timed walking test should be used to evaluate improvement after two weeks. If no benefits are observed, Fampyra should be discontinued.1

    References

    1. Fampyra Summary of Product Characteristics, 2011.
    2. Goodman et al. Lancet 2009; 373: 732–8.
    3. Goodman et al. Ann Neurol 2010; 68: 494–502.

    Source: MIMS Online © Haymarket Publications 1957 – 2011 (04/11/11)

    Conditional approval in EU for Fampyra

    FampyraBiogen Idec Inc. said it received conditional approval from the European Commission for Fampyra to improve walking in adult patients with multiple sclerosis or MS who have walking disability. Fampyra is the first treatment that addresses this unmet medical need with demonstrated efficacy in people with all types of MS.

    Fampyra can be used alone or in combination with disease modifying therapies, including immunomodulatory drugs.

    "With its approval by the European Commission, Fampyra has the potential to make a real difference for thousands of people across Europe with both relapsing remitting and progressive forms of MS," explained Prof. Bernd Kieseier, Department of Neurology, University Hospital Duesseldorf.

    Moreover, Ron Cohen, M.D., Acorda's President and CEO stated, "Studies have shown that even small degrees of walking impairment can have a major negative impact on the patient. The European approval of Fampyra allows people with MS in the European Union to have access to a novel therapy that has been shown to improve walking ability across a wide range of impairment, from mild to severe."

    Fampyra would be available in Europe, on a country-by-country basis, beginning with Germany in September 2011, with other countries following.

    Source: RTT News Copyright © 2011 RTTNews. (25/07/11)

    Ampyra® shows improvement of patient-reported walking ability

    AmpyraAcorda Therapeutics, Inc. announced an analysis of pooled clinical trial results showed patients who were responders to Ampyra® (dalfampridine) Extended Release Tablets, 10 mg demonstrated clinically relevant improvements in walking ability as measured by patient self-report on the 12-Item Multiple Sclerosis Walking Scale (MSWS-12), regardless of either their baseline Expanded Disability Status Scale (EDSS) score or baseline walking speed.

    The data were presented at the 2011 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held June 1-4 in Montreal, Canada. Ampyra is an oral medication approved by the U.S. Food and Drug Administration (FDA) as a treatment to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed.

    "People with MS often experience a progressive decline in their walking ability that can begin early in their disease course. However, in many cases patients and their healthcare providers do not discuss walking impairment until it is so severe that it requires physical support from canes or walkers,” said Ron Cohen, M.D., Acorda's President and CEO. “These data show that people with MS, even those with less obvious walking impairment, can potentially experience meaningful clinical benefit from treatment with Ampyra.”

    The poster presentation, entitled “Impact of Dalfampridine on MSWS-12 Score Change in MS Patients” (poster S70), examined improvements in walking ability as measured by the MSWS-12 when patients were stratified using two separate criteria: EDSS score and baseline walking speed as measured by the Timed 25-Foot Walk (T25FW). The MSWS-12 is a patient-reported questionnaire that assesses the impact of MS on various aspects of walking ability in everyday life. The presentation was based on a pooled analysis of data from one Phase 2 and two Phase 3 clinical trials of dalfampridine, which were the pivotal trials included in the New Drug Application that formed the basis of the U.S. Food and Drug Administration approval of the drug.

    When stratified by baseline EDSS score (≤4.5, 5.0-5.5, ≥6.0), improvements in MSWS-12 scores among Ampyra responders were clinically relevant and substantially greater compared to non-responders and placebo-treated patients across all three EDSS groups. Responders were defined as patients whose walking speed was faster on at least 3 of 4 on-treatment visits than their fastest speed at any of 5 off-treatment visits.

    Similarly, when patients were stratified into four groups by baseline walking speed, Ampyra responders experienced clinically relevant improvements across all four groups.

    A second poster on Ampyra data presented at the CMSC meeting, “UTI Incidence Among MS Patients Treated with Dalfampridine 10 mg Twice Daily” (poster S157), analyzed the incidence of urinary tract infection (UTI) reported by MS patients treated with Ampyra in clinical trials, extension studies, and postmarketing safety reports. Approximately 80% of newly diagnosed MS patients and up to 96% of patients who have had MS for 10 years or more normally experience some bladder dysfunction, and UTI is a frequent complication of this dysfunction1.

    In the pooled Phase 2 and Phase 3 clinical trial data of 400 patients receiving Ampyra twice daily and 238 patients receiving placebo referenced above, 14.5% of Ampyra-treated patients reported experiencing a UTI compared to 9.2% of placebo-treated patients over treatment observations periods of 9 to 14 weeks. The incidence of serious UTIs was similar across the Ampyra and placebo groups; there were no discontinuations in the clinical trials due to UTI as an adverse event. Neither urinalysis nor culture was required for a UTI diagnosis in the clinical trials, which was usually based on symptoms. Among 483 patients who enrolled in Ampyra open-label extension studies, UTI was reported in 33.1% of patients, with observation periods ranging from 1-182 weeks.

    Postmarketing safety reports showed that 0.5% of Ampyra-treated patients reported symptoms suggestive of a UTI (238/46,000 patients; data through April 2011); less than 10% of these reported UTIs were confirmed by urinalysis or culture, suggesting that most diagnoses were based on symptoms rather than recommended diagnostic criterion.

    Ampyra is marketed in the United States by Acorda Therapeutics, Inc. It is approved in the Unites States as a treatment to improve walking in people with MS. This was demonstrated by an increase in walking speed.

    Source: Acorda Therapeutics (06/06/11)

    EU agency recommends conditional approval for MS drug Fampyra

    FampyraReversing an earlier decision, European regulators have recommended approving Acorda Therapeutics Inc's (ACOR.O) drug Fampyra, which is designed to improve the walking ability of patients with multiple sclerosis.

    Acorda shares jumped 21 percent to $32.33 in premarket trading on Friday.

    The European Medicines Agency, which advises the European Commission on whether to approve new drugs, said in a statement it has recommended giving the drug conditional approval.

    U.S. biotechnology company Biogen Idec Inc acquired European rights to the drug, also known as Ampyra, in 2009 and is in charge of commercialization and marketing it in Europe.

    Conditional approval means Biogen can start selling the product once it is formally approved -- expected within 67 days -- but the company will have to provide additional information once it is on the market. If and when all the conditions are met, it will receive full approval.

    "This is a major milestone for the company," said Ron Cohen, Acorda's chief executive, in an interview.

    The drug was approved in the United States in January, 2010, but in January this year, European advisors rejected the drug, saying they were not convinced it conferred a clinically meaningful benefit.

    Under terms of their agreement, Biogen paid $110 million upfront for the European rights to the product, and agreed to pay up to $400 million more in milestone payments. Acorda will also receive a double-digit percentage royalty. Approval in Europe triggers a $25 million milestone payment to Acorda.

    The European decision is the second piece of good news Acorda has received on the drug recently. In April, the stock jumped 27 percent amid optimism the company will be granted a patent extension on Ampyra, potentially pushing out generic competition beyond 2024.

    Analysts currently see Fampyra/Ampyra reaching sales of around $600 million by 2015, according to Thomson Reuters Pharma consensus forecasts.

    Acorda's shares had fallen nearly 30 percent from their year high last June. Some investors have grown concerned sales of its key medicine have flattened.

    Cohen said the flattening of prescriptions reflected the fact that when the drug was first approved, a large number of patients -- some 40,000 -- rushed to try it. Inevitably, the product did not work for everyone and a proportion of people stopped taking it.

    Now the company is optimistic it can increase sales by marketing the drug for a wider group of patients -- those whose walking ability has not deteriorated as much as those who initially took the drug.

    "Data show that the most mildly affected patients did at least as well as the more severely affected," Cohen said. "Even if you are just beginning to have impairment in your walking abilities you can benefit."

    Source: Reuters © Copyright 2011 Thomson Reuters (20/05/11)

    Approval for Fampyra in Australia

    AmpyraThe Australian Therapeutic Goods Administration (TGA) has granted approval for Fampyra™, (fampridine) 10 mg Modified Release (MR) tablet, for the symptomatic improvement of walking ability in adult patients with multiple sclerosis (MS) who have shown improvement after eight weeks of treatment.

    Fampyra demonstrated efficacy in people with all four major types of MS (relapsing remitting, secondary progressive, progressive relapsing and primary progressive). Fampyra can be used alone or with existing MS therapies, including immunomodulator drugs.

    Biogen Idec is presently taking steps to obtain Pharmaceutical Benefit Scheme (PBS) reimbursement approval for Fampyra, an outcome which will benefit the MS community in Australia. While Biogen Idec follows this reimbursement procedure, Fampyra is expected to be available to patients with a private prescription beginning in October 2011.

    “We are very pleased with the TGA’s decision to approve Fampyra in Australia for people with MS. Studies have shown Fampyra can increase walking speed by 25%, independent of the type of MS, and that this increase is associated with clinically meaningful improvements in overall walking ability” said Norman Putzki, Director Development at Biogen Idec.

    Fampyra is an oral potassium channel blocker which is thought to work by stopping potassium leaving the nerve cells which have been damaged by MS. This enables signals to pass down the nerve more regularly, which may allow patients to walk better.

    In the two Phase III clinical trials, a significantly greater portion (p<0.001) of Fampyra-treated patients had a consistent improvement in walking speed when compared to placebo (34.8 percent vs. 8.3 percent and 42.9 percent vs. 9.3 percent, respectively). The increased response rate in the Fampyra group was observed across all types of MS included in the studies.

    The Fampyra treated patients who had consistent improvement in the two studies experienced an average increase in walking speed of 25.2 percent and 24.7 percent compared to 4.7 percent and 7.7 percent, respectively, for the placebo-treated patients.

    The majority of the study participants in these trials were also taking immunomodulatory drugs, including interferons, glatiramer acetate, and natalizumab; however the magnitude of improvement in walking ability was independent of concomitant therapy.

    Patients confirmed the clinical meaningfulness of improved walking using the 12-item Multiple Sclerosis Walking Scale (MSWS-12), a patient-based questionnaire measuring the impact of walking impairment on a patient’s ability to perform everyday activities.

    Source: Financial Post © © 2011 National Post.  (16/05/11)

    New Ampyra data analyses on walking improvement in MS

    AmpryraAcorda Therapeutics, Inc. today announced data analyses showing that people with multiple sclerosis (MS) who responded to Ampyra™ (dalfampridine) Extended Release Tablets, 10 mg had comparable improvements in their walking regardless of baseline walking speed or overall level of MS-related disability1.

    In addition, Ampyra responders, regardless of baseline disability, showed clinically meaningful improvement on the 12-Item MS Walking Scale (MSWS-12), a patient-based questionnaire that measures the impact of MS on the patient's reported ability to perform daily activities related to walking. These and other post hoc analyses of Ampyra clinical trial and extension study data will be presented at the 63rd American Academy of Neurology (AAN) Annual Meeting being held April 9-16 in Honolulu, Hawaii.

    "These new analyses of our clinical data highlight that people with MS can experience a meaningful benefit with Ampyra across all degrees of walking impairment. This also applies to patients with walking difficulties that may be less obvious and not immediately appreciated by others."

    "Walking impairment is one of the most common and serious functional deficits caused by MS, but often people with MS and their physicians do not discuss walking issues until the level of impairment is severe," said Ron Cohen, M.D., Acorda's President and CEO. "These new analyses of our clinical data highlight that people with MS can experience a meaningful benefit with AMPYRA across all degrees of walking impairment. This also applies to patients with walking difficulties that may be less obvious and not immediately appreciated by others."

    As part of this analysis, 394 participants who received 10 mg twice daily in Ampyra Phase 2 and Phase 3 clinical trials were stratified by two separate criteria: baseline Expanded Disability Status Scale (EDSS) score (five sub-groups: 1.5-3.5; 4.0-4.5; 5.0-5.5; 6.0; and >6.0) and baseline walking speed as measured by the number of seconds required to complete the Timed 25 Foot Walk (T25FW) (five sub-groups: 5.16-8.95; 8.98-10.61; 10.64-13.29; 13.33-18.38; 18.40-71.57).

    A Timed Walk responder was defined as a person who walked faster on at least three of four on-treatment assessments compared to the fastest of five off-treatment assessments as measured by the T25FW. When stratified by severity of EDSS score, both the rate of response and the average percent improvement in walking speed among Ampyra Timed Walk responders were comparable across the five subgroups and were consistently greater than changes in both Ampyra non-responders and patients receiving placebo.

    A separate analysis of pooled data from two placebo-controlled Ampyra Phase 3 clinical trials demonstrated that Ampyra responders transitioning from the placebo-controlled trials into open-label studies experienced a rapid loss of walking improvement after discontinuing therapy during the transition period2. Re-initiation of therapy resulted in recovery of walking speed improvement among previous responders by the first open-label study visit, which occurred 2 weeks after restarting treatment. The average walking speed improvement among responders was 27.7% from baseline at the conclusion of the placebo-controlled trials; after withdrawal from therapy, responder walking speed decreased to 4.3% above baseline. Following re-initiation of therapy, responders showed an average 24.3% increase from the original baseline. This indicates that responders can return to the level of walking improvement experienced before interruption of therapy. The study also found that the safety profile observed in the long-term extension trials was consistent with that seen in double-blind clinical trials; no new safety signals emerged in the open label extension. Approximately 94% of participants who completed the placebo-controlled clinical trials elected to enroll in the extension study. Participants in the extension study were followed for up to 3.5 years on therapy for this analysis.

    Another analysis of Ampyra clinical trial data indicated that the FDA-approved dose of 10 mg taken twice daily is the optimal dose for Ampyra. Data showed that dosage strengths above of 10 mg twice daily did not result in an increase in either responder rates or change in walking speed among responders, but did increase overall adverse events (AEs) and central nervous system AEs3. In a placebo-controlled Phase 2 clinical trial (MS-F202) that evaluated the safety and efficacy of Ampyra dosed at 10, 15 and 20 mg twice daily, data showed that there was no statistically significant difference in the proportion of patients who met the criteria for Ampyra Timed Walk responders across the three dosages relative to placebo (35.3% for 10 mg; 36.0% for 15 mg; 38.6% for 20 mg; 8.5% for placebo). The same study showed comparable changes between the three twice daily dosages in terms of improvement of walking speed among responders (27.6% for 10 mg; 29.6% for 15 mg; 24.6% for 20 mg). The overall rate of adverse events in the MS-F202 was higher among patients receiving 15 and 20 mg twice daily compared to those receiving 10 mg twice daily (86.5% for 10 mg; 94.0% for 15 mg; 91.2% for 20 mg; 80.9% placebo), as was the incidence of central nervous system AEs (38.5% for 10 mg; 50.0% for 15 mg; 63.2% for 20 mg; 44.7% placebo). Additional data presented in this analysis showed that improvements in the percent change in walking speed were correlated to drug levels in the blood below the average minimum level with the 10 mg dose, indicating that doses lower than 10 mg twice daily would not be expected to maintain therapeutic plasma concentrations without more frequent dosing.

    Ampyra is marketed in the United States by Acorda Therapeutics, Inc. It is approved in the Unites States as a treatment to improve walking in people with MS. This was demonstrated by an increase in walking speed.

    1 Improvement in Walking Speed Across a Wide Range of Baseline EDSS Scores and Walking Speeds From Trials of Dalfampridine Extended Release Tablets in Patients with MS (P07.164) available for viewing on April 14 from 2-6:30 p.m. HAST

    2 Change in Walking Speed in Transition From Double-Blind to Open-Label Clinical Trials of Dalfampridine Extended Release Tablets, 10 mg Twice Daily, in Patients With MS (P07.165) available for viewing on April 14 from 2-6:30 p.m. HAST

    3 Doses of Dalfampridine Extended Release Tablets Greater Than 10 mg Twice Daily Are Associated With Increased Adverse Events but not Increased Efficacy (P03.236) available for viewing on April 12 from 2-6:30 p.m. HAST

    Source: Medical News Today © 2004-2011 MediLexicon International Ltd (12/04/11)

    IND filed for AVP-923 for central neuropathic pain in MS

    Avanir LogoAvanir Pharmaceuticals, Inc. (NASDAQ: AVNR) today announced that it has filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) to begin a large Phase II clinical trial of AVP-923, an investigational drug for the treatment of central neuropathic pain in patients with multiple sclerosis (MS).

    The FDA has acknowledged receipt of the submission and the company expects that the IND filing will be subject to standard 30-day review.

    "Over half of MS patients suffer from chronic and debilitating pain, with a substantial negative impact on their quality of life. With no FDA-approved therapies to treat central neuropathic pain in MS patients, this represents an area of high unmet medical need," said Randall Kaye, MD, Chief Medical Officer of Avanir Pharmaceuticals. "The team at Avanir has done an exemplary job of designing and developing a program to explore the potential of AVP-923 in MS-related pain as well as other important endpoints including fatigue, sleep quality and cognition. We are excited about the potential of this compound, which may ultimately represent a new approach to treating central neuropathic pain in MS patients."

    "This marks the third IND for the NUEDEXTA/AVP-923 program and demonstrates our belief that the dual sigma-1 receptor agonist and NMDA receptor antagonist binding profile has significant potential beyond PBA," said Keith A. Katkin, President and CEO of Avanir Pharmaceuticals. "In addition, we intend to file another IND within the next year to begin studying the potential use of AVP-923 in other forms of emotional lability – specifically anger, irritability, and other behavioral symptoms of dementia."

    About the Study
    The objectives of the study are to evaluate the safety, tolerability, and efficacy of three dose levels of AVP-923 capsules for the treatment of central neuropathic pain in a population of patients with multiple sclerosis. AVP-923 is a combination of dextromethorphan (DM) and quinidine (Q). The trial is a multicenter, randomized, double-blind, placebo-controlled, 4-arm parallel group study. Eligible patients will be randomized to receive one of the three dose levels of AVP-923 containing either 45mg DM/10 mg Q, 30mg DM/10mg Q, 20mg DM/10mg Q or placebo, daily for 12 weeks. The primary efficacy endpoint is the Pain Rating Scale obtained from daily patient diaries. Secondary endpoints include measures of fatigue, disability, impact of MS on daily life, sleep quality, cognition and depression. Safety will be assessed by monitoring adverse events, clinical laboratory tests, ECGs, physical examinations, and vital signs.

    The filing of this IND represents the next step in Avanir's plan to broadly develop AVP-923 for conditions of the central nervous system (CNS). Avanir expects to enroll approximately 400 patients at 65 centers both in the US and internationally. The company anticipates enrolling the first patient into the trial before the end of 2011.

    About Multiple Sclerosis and Central Neuropathic Pain
    Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system (CNS) characterized by numerous disabling symptoms, including abnormal function of the motor, sensory and visual systems. Pain and fatigue are two of the most common symptoms related to disability in MS patients, often leading to social isolation and inability to work. The initial disease course often demonstrates multiple exacerbations and remissions, with the variety of symptoms determined by the location of the plaques in the brain and spinal cord. Among the many symptoms and types of disabilities associated with MS, chronic pain has an important impact on daily life of patients with this disease and may affect work retention in this population. Pain in MS patients may be induced by a variety of mechanisms including musculoskeletal disorders, spasms and trigeminal neuralgia, but central neuropathic pain due to the involvement of sensory pathways is the most frequent, estimated to affect over 55% of patients.

    An important type of MS-related pain is central neuropathic pain. Central pain can be defined as pain in a neurologic distribution with altered sensation and no evidence of peripheral neuropathy. In one study, 55% of people with MS had "clinically significant pain" at some time. Almost half (48%) were troubled by chronic pain.

    About AVP-923
    AVP-923 is a combination of two well-characterized compounds: the active ingredient dextromethorphan hydrobromide (an uncompetitive NMDA receptor antagonist and sigma-1 agonist) and the enzyme inhibitor quinidine sulfate (a CYP450 2D6 inhibitor), which serves to increase the bioavailability of dextromethorphan.

    The dosage form of AVP-923 of 20 mg DM/10 mg Q (twice daily) is approved by the FDA under the brand name NUEDEXTA™ capsules which is indicated for the treatment of pseudobulbar affect (PBA).

    About NUEDEXTA
    NUEDEXTA™ is the first and only FDA-approved treatment for pseudobulbar affect (PBA). NUEDEXTA is an innovative combination of two well-characterized components; dextromethorphan hydrobromide (20 mg), the ingredient active in the central nervous system, and quinidine sulfate (10 mg), a metabolic inhibitor enabling therapeutic dextromethorphan concentrations. NUEDEXTA acts on sigma-1 and NMDA receptors in the brain, although the mechanism by which NUEDEXTA exerts therapeutic effects in patients with PBA is unknown.

    NUEDEXTA is indicated for the treatment of pseudobulbar affect (PBA). PBA occurs secondary to a variety of otherwise unrelated neurological conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying. PBA episodes typically occur out of proportion or incongruent to the patient's underlying emotional state. Studies to support the effectiveness of NUEDEXTA were performed in patients with amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS).

    NUEDEXTA has not been shown to be safe and effective in other types of emotional lability that can commonly occur, for example, in Alzheimer's disease and other dementias. The primary outcome measure, laughing and crying episodes, was significantly lower in the NUEDEXTA arm compared to placebo. The secondary outcome measure, the Center for Neurologic Studies Lability Scale (CNS-LS), demonstrated a significantly greater mean decrease in CNS-LS score from baseline for the NUEDEXTA arm compared to placebo.

    Source: Avanir Pharmaceuticals, Inc. (04/04/11)

    MS drug Fampyra receives negative opinion from the CHMP

    FampyraBiogen Idec announced today that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a negative opinion recommending against approval of FAMPYRA® (prolonged-release fampridine 10 mg tablets) to improve walking ability in adult patients with multiple sclerosis (MS) in the European Union.

    Biogen Idec intends to appeal this opinion and request a re-examination of the decision by the CHMP.

    “About two-thirds of MS patients report difficulty in walking due to their disease1,2, and currently there is no therapy approved in Europe to address this high unmet medical need,” said Alfred Sandrock, M.D., Ph.D., Head of Neurology Research & Development at Biogen Idec. “Tens of thousands of people with MS have already received the therapy in the United States, where it is approved, and many have reported important benefits. We will work closely with the CHMP during the appeal process to address the Committee’s concerns, with the goal of making this important medication available to MS patients in Europe.”

    As a leader in MS with two MS medications on the market and six potential MS therapies in the pipeline, Biogen Idec has significant scientific expertise in MS and is committed to improving the lives of patients living with this disease.

    As of the end of September 2010, approximately 6300 prescribers had initiated approximately 31,000 MS patients on prolonged-release fampridine tablets treatment in the United States (U.S.), where the drug is commercialized by its developer, Acorda Therapeutics, Inc., under the trade name AMPYRA® (dalfampridine) Extended Release Tablets, 10 mg.

    AMPYRA was approved by the U.S. Food and Drug Administration on January 22, 2010.

    Source: Euroinvestor Copyright Euroinvestor A/S 2011 (21/01/11)

    Additional phase 3 clinical trial data for Ampyra released

    AmpyraAcorda Therapeutics, Inc. today announced that data from the second of two pivotal dalfampridine extended release tablets Phase 3 clinical trials in multiple sclerosis (MS) were published in the October 2010 edition of Annals of Neurology.

    The study, which included 239 participants at 39 leading MS centers in the U.S. and Canada, demonstrated that a significantly greater proportion of people with MS taking dalfampridine extended release tablets had a consistent improvement in walking speed compared to those receiving placebo tablets (42.9 percent vs. 9.3 percent; p < 0.0001). These results were consistent with data from the first pivotal Phase 3 clinical trial, which were published in the February 29, 2009 edition of The Lancet.

    "Data from this Phase 3 clinical trial involving 239 people with MS confirmed prior study results that a statistically significant proportion of those who receive dalfampridine extended release tablets experience a consistent improvement in their walking speed, and that this improvement is clinically meaningful," said the paper's lead author Andrew Goodman, M.D., Director of the Multiple Sclerosis Center at the University of Rochester Medical Center(1).

    AMPYRA(R) (dalfampridine) Extended Release Tablets, 10 mg was approved by the U.S. Food and Drug Administration (FDA) on January 22, 2010 as a treatment to improve walking in people with MS. This was demonstrated by an increase in walking speed.

    "Walking is an essential function of daily life. Published surveys have shown that over 60 percent of MS patients have walking impairment at any given time, and that people with MS cite walking impairment as one of the most upsetting aspects of their disease. AMPYRA is the only therapy approved to improve walking in MS, and it can provide a significant benefit for those who respond to treatment," said Ron Cohen, M.D., President and CEO of Acorda Therapeutics. "Since the launch of AMPYRA in March 2010, we have been gratified by the positive feedback we have received from patients, as well as their family members and health care providers. We are continuing to work with these communities to provide information about the appropriate use of AMPYRA."

    Primary data from this clinical trial were first presented at the 2008 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual meeting. Data from this study are included in the approved package insert for AMPYRA(R) (dalfampridine) Extended Release Tablets, 10 mg.

    Data Demonstrate Improvement in Walking Speed

    A significantly greater proportion of people taking dalfampridine (42.9 percent vs. 9.3 percent) were classified as "Timed Walk Responders," defined as subjects with a faster walking speed in at least three of the four on-drug clinical visits compared to the fastest walking speed during five off-drug visits, as measured by the Timed 25-Foot Walk. The average increase in walking speed over the 9-week treatment period compared to baseline was 24.7 percent for the Timed Walk Responders in the drug group vs. 7.7 percent for the placebo group; the increase in speed was maintained across the entire treatment period and seen across all four major types of MS.

    In addition, the study measured improvement in leg strength using the Lower Extremity Manual Muscle Test (LEMMT). There was an improvement seen in the dalfampridine Timed Walk Responders (p=0.028) compared to placebo. The mean improvement among dalfampridine Timed Walk Non-responders was not significantly different from either the dalfampridine Timed Walk Responder or placebo groups.

    Validating the Clinical Meaningfulness of Walking Improvement

    The study included several validation measures in order to assess the clinical meaningfulness of consistently improved walking speed (i.e. the Timed Walk Response). The 12-Item MS Walking Scale (MSWS-12) was used as the primary measure to validate the clinical meaningfulness of the Timed Walk Response. The MSWS-12 is a self-rated scale in which the patient rates the extent to which their MS has affected 12 activities related to walking over the preceding two weeks, There was a significantly greater average improvement from baseline among Timed Walk Responders compared to Non-responders (p<0.001).

    A Subject Global Impression (SGI) and a Clinician Global Impression (CGI) were used as secondary validation measures. Significant improvements were seen on these measures among Timed Walk Responders compared to Timed Walk Non-responders.

    Safety Profile

    In this study, adverse events were largely consistent with the safety profile observed in previous studies of dalfampridine extended release tablets in people with MS. Eight patients, including four from each treatment group (3.3 percent dalfampridine, 3.4 percent placebo) withdrew from the study due to adverse events. There was one reported seizure-related event in the placebo group (complex partial seizure) and no seizure-related events reported in the dalfampridine group.

    Following is a list of adverse events reported in the clinical trial that occurred in greater than 5 percent of patients taking dalfampridine (percentages represent the dalfampridine treatment group vs. the placebo group): urinary tract infection (17.5 percent vs. 8.4 percent), falls (11.7 percent vs. 16.8 percent), insomnia (10.0 percent vs. 1.7 percent), headache (9.2 percent vs. 0.8 percent), asthenia (8.3 percent vs. 4.2 percent), dizziness (8.3 percent vs. 4.2 percent), nausea (8.3 percent vs. 0.8 percent), back pain (5.8 percent vs. 2.5 percent), balance disorder (5.8 percent vs. 1.7 percent), upper respiratory tract infection (5.8 percent vs. 6.7 percent), arthralgia (5.0 percent vs. 4.2 percent), nasopharyngitis (5.0 percent vs. 4.2 percent) and paresthesia (5.0 percent vs. 1.7 percent).

    Clinical Trial Design

    The double-blind, placebo-controlled clinical trial was designed to evaluate the safety and efficacy of dalfampridine in improving walking ability in people with MS. The study randomized 239 patients between 18 and 70 years old with a definite diagnosis of MS and some degree of walking disability. The study was open to people with all types of MS, including primary-progressive, secondary-progressive, relapsing-remitting and progressive-relapsing. Participants were permitted to remain on a stable regimen of their current medications, including immunomodulators, such as interferons. Subjects were randomized to 9 weeks of treatment with dalfampridine (n=120) or placebo (n=119), a 1:1 ratio of drug to placebo.

    (1) Dr. Goodman is a consultant to Acorda Therapeutics.

    Source: Acorda Therapeutics, Inc. (17/11/10)

    New Ampyra(R) (dalfampridine) study data reported at ECTRIMS

    AmpyraResponders to Ampyra Showed Clinically Significant and Meaningful Improvement in Walking Ability Based on Recent Consensus Expert Group Criteria.

    Acorda Therapeutics, Inc. today announced that a new analysis of AMPYRA(R) (dalfampridine) Extended Release Tablets, 10 mg data examining walking improvement in treatment responders has been presented at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Ampyra is an oral medication approved by the U.S. Food and Drug Administration (FDA) as a treatment to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an increase in walking speed.

    Using recently published consensus expert group criteria(1) , an independent analysis of pooled Ampyra Phase 3 trial data showed that the statistically significant improvement in Multiple Sclerosis Walking Scale (MSWS-12) score reported in the pivotal studies is also clinically significant and meaningful for people with MS. This new analysis indicates that the MSWS-12 score differences, 7.30 points between Ampyra responders and placebo, and 7.02 points between Ampyra responders and all non-responders, exceed the consensus expert group criteria and thereby satisfy the requirements for clinically significant and meaningful differences.

    An Ampyra responder was defined as a person who walked faster on the Timed 25-Foot Walk at 3 of 4 on-treatment assessments than at any of the 5 off-treatment assessments.

    "Walking is a critical function, and walking disability is often cited by people with MS as the most concerning aspect of their disease," said Ron Cohen, M.D., President and CEO of Acorda Therapeutics. "This study highlights that the MSWS-12 is an important tool in evaluating how walking improvements can translate into real world benefit to patients, and that patients who respond to Ampyra can experience a clinically meaningful improvement in their walking."

    Acorda is developing and commercializing Ampyra in the United States. Biogen Idec has licensed the rights to develop and commercialize prolonged-release fampridine tablets outside the United States from Acorda Therapeutics, Inc. Biogen Idec is presenting additional clinical data on prolonged-release fampridine at ECTRIMS.

    This study was conducted by Dr. Jeremy Hobart, Peninsula College of Medicine and Dentistry (Devon, UK) and funded by Acorda Therapeutics, Inc.

    Important Safety Information

    Ampyra can cause seizures; the risk of seizures increases with increasing Ampyra doses. Ampyra is contraindicated in patients with a prior history of seizure. Discontinue Ampyra use if seizure occurs.

    Ampyra is contraindicated in patients with moderate or severe renal impairment (CrClless-than or equal to 50 mL/min); the risk of seizures in patients with mild renal impairment (CrCl 51--80 mL/min) is unknown, but Ampyra plasma levels in these patients may approach those seen at a dose of 15 mg twice daily, a dose that may be associated with an increased risk of seizures; estimated CrCl should be known before initiating treatment with Ampyra.

    Ampyra should not be taken with other forms of 4-aminopyridine (4-AP, fampridine), since the active ingredient is the same.

    Urinary tract infections were reported more frequently as adverse reactions in patients receiving Ampyra 10 mg twice daily compared to placebo.

    The most common adverse events (incidence greater-than or equal to 2% and at a rate greater than the placebo rate) for Ampyra in MS patients were urinary tract infection, insomnia, dizziness, headache, nausea, asthenia, back pain, balance disorder, multiple sclerosis relapse, paresthesia, nasopharyngitis, constipation, dyspepsia, and pharyngolaryngeal pain.

    Source: MarketWatch Copyright Business Wire 2010 (15/10/10)

    New Ampyra data released at AAN Annual meeting

    AmpyraResponders to Ampyra treatment for MS showed improvement in average walking speed compared to their average baseline for up to 2.5 years in open-label studies

    Pooled Data from Phase 2 and 3 Placebo-Controlled Studies Showed 37% of Ampyra-Treated Patients Demonstrate Consistent Walking Improvement and 25% Average Increase in Walking Speed

    --Pooled Phase 2 and 3 Data Also Showed Ampyra Improves Walking Speed Across the Range of Baseline Walking Speeds Studied and Response is Independent of Patient Demographics and Concomitant Immunomodulator Use

    Acorda Therapeutics, Inc. announced that four new analyses of clinical trial data on Ampyra(TM) (dalfampridine) Extended Release Tablets 10 mg are being presented at the 62nd American Academy of Neurology (AAN) Annual meeting. Ampyra is an oral medication approved by the U.S. Food and Drug Administration (FDA) on January 22, 2010 as a treatment to improve walking in patients with multiple sclerosis (MS). This was demonstrated by an improvement in walking speed.

    "Ampyra is a new therapy, the first ever with an indication to improve walking in MS," said Ron Cohen, M.D., President and CEO of Acorda Therapeutics. "The data being presented at the AAN meeting include analyses of large numbers of patients receiving therapy for up to two and a half years, providing new information on the safety and efficacy of the drug during chronic use."

    Two platform presentations on Ampyra data are included in today's Scientific Session on Multiple Sclerosis:

    Platform Presentation - Extension Studies

    The first presentation is an analysis of long-term data from open-label extension studies of two completed Phase 3 trials as of November 30, 2008, the cut-off date for the safety update for the New Drug Application (NDA) of Ampyra. Patients receiving AMPYRA in the placebo-controlled trials were classified as either Timed Walk responders or non-responders based on their walking speed change as measured by the Timed 25-Foot Walk. A Timed Walk responder was defined as a patient who showed faster walking speed for at least 3 of 4 visits while taking Ampyra compared to the fastest of 5 off-drug visits.

    In the longer of the two extension studies, Ampyra Timed Walk responders as a group continued to show improvement over their average baseline walking speed after 2.5 years, while Timed Walk non-responders did not. Both Timed Walk responders and non-responders showed a gradual and similar decrease in walking speed over time. Similar results were seen in the shorter extension study after 1.2 years. In both extension studies, the safety profile of Ampyra was similar to that observed in double-blind trials lasting up to 14 weeks.

    In the longer of the two extension trials, the approximate total exposure to Ampyra was 565 patient-years as of the cut-off date and there were four seizure-related events, with a fifth patient experiencing a seizure 22 days after discontinuation of study drug. There were no reports of seizure in the shorter of the two extension trials as of the cut-off date, with 193 patient-years of exposure to Ampyra.

    Platform Presentation - Double Blind Studies

    The second platform presentation is a pooled efficacy analysis of 631 patients who participated in one Phase 2 and two Phase 3 AMPYRA clinical trials (394 patients received Ampyra 10 mg twice daily; 237 received placebo). Across the three studies, 37.3% of patients who received Ampyra qualified as Timed Walk responders compared to 8.9% of patients who received placebo. The Ampyra-treated responders showed an average improvement in walking speed of 25.3%.

    In addition, Ampyra-treated patients who did not respond to therapy experienced changes from baseline that were similar to those in the placebo group, indicating the trial design effectively separated treatment effects from unrelated changes in disease course.

    Poster Presentations

    The pooled Phase 2 and Phase 3 data were also analyzed in two separate poster presentations that will be presented on Thursday, April 15. The first analysis showed that response to Ampyra was independent of gender, age, body mass index, MS type, baseline disability score as measured by the Expanded Disability Status Scale (EDSS), or disease duration. Response rate was also independent of treatment with common immunomodulator drugs. Among patients who responded to Ampyra, 36.8% were taking interferons, 37.1% were taking glatiramer acetate and 27.3% were taking natalizumab; 39.8% were not taking immunomodulator therapy.

    A second analysis compared response to Ampyra in patients based on baseline walking speed, which ranged from 0.3-4.8 feet per second. The responder rate and percent improvement in walking speed in patients treated with Ampyra were similar across the entire range of baseline walking speeds represented in the studies.

    Important Safety Information

    Ampyra can cause seizures; the risk of seizures increases with increasing Ampyra doses. Ampyra is contraindicated in patients with a prior history of seizure. Discontinue Ampyra use if seizure occurs.

    Ampyra is contraindicated in patients with moderate or severe renal impairment (CrClless-than or equal to 50 mL/min); the risk of seizures in patients with mild renal impairment (CrCl 51--80 mL/min) is unknown, but Ampyra plasma levels in these patients may approach those seen at a dose of 15 mg twice daily, a dose that may be associated with an increased risk of seizures; estimated CrCl should be known before initiating treatment with Ampyra.

    Ampyra should not be taken with other forms of 4-aminopyridine (4-AP, fampridine), since the active ingredient is the same.

    Urinary tract infections were reported more frequently as adverse reactions in patients receiving Ampyra 10 mg twice daily compared to placebo.

    The most common adverse events (incidence greater-than or equal to 2% and at a rate greater than the placebo rate) for Ampyra in MS patients were urinary tract infection, insomnia, dizziness, headache, nausea, asthenia, back pain, balance disorder, multiple sclerosis relapse, paresthesia, nasopharyngitis, constipation, dyspepsia, and pharyngolaryngeal pain.

    Source: Acorda Therapeutics, Inc. (13/04/10)

    FDA clears Acorda drug, Ampyra, for improved walking in Multiple Sclerosis

    Acorda LlogoFederal health regulators have approved an Acorda Therapeutics pill to improve walking in patients multiple sclerosis, an often disabling disease that affects the nervous system.

    The Food and Drug Administration said Friday Ampyra is the first drug approved to help multiple sclerosis patients walk.

    About 400,000 patients in the U.S. have the disease, which affects the brain and nervous system, causing loss of balance, muscle spasms and other movement problems.

    Between 260,000 and 340,000 of those patients have difficulty walking, and could be eligible for the new drug, according to company officials.

    Acorda, based in Hawthorne, N.Y., conducted two trials tracking patients' ability to complete a 25-foot walking exercise. Both studies showed improvements in time needed to complete the exercise. While those gains were often just a fraction of a second, Acorda CEO Ron Cohen said that on average, patients' times improved by 25 percent after taking Ampyra.

    Cohen said the company will launch Ampyra in the U.S. in March. He added that the pill could be combined with older medications designed to slow the progression of multiple sclerosis.

    Ampyra will be manufactured under a license with Irish drugmaker Elan Corp., which developed the extended-release formulation for the pill. Acorda will market and distribute the drug in the U.S.

    Company shares jumped $2.50, or 9.8 percent, to close at $28.12 Friday, adding 13 cents in after-hours trading.

    In its announcement posted online, the FDA warned that Ampyra can cause seizures when given at higher-than-recommended doses — anything over 10 mg. Company studies showed that doses above 10 mg increased seizure risk but did not increase the drug's effectiveness.

    The FDA said the drug should also not be given to patients with moderate to severe kidney disease, as they are at greater risk of seizures.

    Other side effects reported in clinical trials included: insomnia, urinary tract infections, dizziness, headache, nausea and throat pain, according to the FDA.

    Source: ABC News Copywrite ABC News.com 2010 (23/01/10)

    European application for Fampridine-PR tablets to aid walking in Multiple Sclerosis submitted

    Biogen logoBiogen Idec has announced the submission of a marketing authorization application (MAA) to the European Medicines Agency for Fampridine Prolonged Release (Fampridine-PR) tablets, a novel oral therapy for the improvement of walking ability in adult patients with multiple sclerosis (MS).

    The company also has filed a New Drug Submission (NDS) to Health Canada. "Walking impairment has a significant impact on the lives of many people living with MS," said Alfred Sandrock, MD, PhD, Senior Vice President, Neurology Research and Development, Biogen Idec.

    "Fampridine-PR tablets may offer a novel approach to address this debilitating aspect of the disease by improving the walking ability of MS patients. We look forward to working with regulators to make this therapy available to people with MS in Europe and Canada."

    The MAA submission and Canadian NDS are based on a comprehensive development program including results from two Phase III, randomized, double-blind, placebo-controlled studies. These studies demonstrated the efficacy of Fampridine-PR tablets in improving walking ability in patients with relapsing-remitting, secondary progressive, progressive relapsing, and primary progressive MS.

    In the two Phase III clinical trials, a significantly greater portion (p<0.001) of Fampridine-PR-treated patients had a consistent improvement in walking speed when compared to placebo (34.8 percent vs. 8.3 percent and 42.9 percent vs. 9.3 percent, respectively). The increased response rate of the Fampridine-PR group was observed across all types of MS included in the studies.

    The Fampridine-PR treated subjects who had consistent improvement in the two studies experienced an average increase in walking speed of 25.2 percent and 24.7 percent compared to 4.7 percent and 7.7 percent, respectively, for the entire placebo group.

    The majority of the study participants in these trials were using immunomodulatory drugs, including interferons, glatiramer acetate, and natalizumab; however the magnitude of improvement in walking ability was independent of concomitant therapy.

    Source: Biogen Idec (14/01/10)

    FDA delays ruling on MS drug, Fampridine-SR, until January 2010

    Acorda LogoAcorda Therapeutics Inc. said the Food and Drug Administration delayed a ruling on its multiple sclerosis drug candidate Fampridine-SR by three months.

    The agency was due to make a decision by today, 22/10, but the ruling is now due by Jan. 22, 2010.

    Acorda said the FDA extended its review because it recently submitted new information on its risk evaluation strategy for the drug.

    Acorda sent in the additional information following a meeting with an FDA panel on Oct. 14. The panel recommended that Fampridine-SR receive FDA approval.

    Source: The Associated Press Copyright 2009 The Associated Press. All rights reserved. (22/10/09)

    Positive vote by FDA advisory committee for Fampridine-SR

    Acorda LogoAcorda Therapeutics, Inc. has announced the U.S. Food and Drug Administration (FDA) Peripheral and Central Nervous System Drugs (PCNSD) Advisory Committee voted 12 to 1 that clinical data on Fampridine-SR 10 mg twice daily demonstrated substantial evidence of effectiveness as a treatment to improve walking in people with multiple sclerosis (MS) and voted 10 to 2 (1 abstention) that it is clinically meaningful and can be safe for use.

    "We are pleased with the outcome of today`s Advisory Committee meeting. People with MS have an urgent need for therapies to improve their walking, which is essential to conducting their activities of daily life. If approved, Fampridine-SR would be the first medicine to improve walking in people with MS," said Ron Cohen, M.D., Acorda Therapeutics President and CEO. "This Advisory Committee meeting is an important milestone in the development of Fampridine-SR, and we look forward to working with the FDA as it completes its review of Acorda`s New Drug Application."

    The Committee also recommended by a vote of 12 to 1 that Acorda be required to evaluate the effects of doses lower than 10 mg twice daily, but by a 10 to 2 vote (1 abstention) that these studies not be required prior to approval.

    At the request of the FDA, the Committee discussed possible conditions for use, including for patients with renal impairment or history of seizure. Acorda has proposed a Risk Evaluation and Mitigation Strategy (REMS) program, which could include healthcare professional and patient education around appropriate use of Fampridine-SR.

    The FDA seeks the advice of an advisory committee such as the PCNSD when evaluating a potential new treatment, but is not required to follow its recommendation. The current Fampridine-SR Prescription Drug User Fee Act (PDUFA) date set by the FDA is October 22, 2009; the PDUFA date is the target date for the FDA to complete its review of Fampridine-SR.

    Source: Acorda Therapeutics, Inc. (15/10/09)

    Multiple Sclerosis drug Fampridine-SR may need more study, U.S. FDA says

    Acorda LogoAcorda Therapeutics Inc.’s pill to help multiple sclerosis patients walk faster may not have fully proven its effectiveness, according to a U.S. review. 

    Food and Drug Administration reviewers said they had “doubts about the validation” of the trial design for the drug, Fampridine-SR, in a report posted today on the agency’s Web site. An FDA advisory panel will meet Oct. 14 in Adelphi, Maryland, to discuss if the drug’s benefits are “clinically meaningful” and whether they justify the risk of seizures.

    MS strikes more than 2.5 million people worldwide and is caused by damage to myelin, the protective sheath around nerve cells in the brain and spinal cord, according to the National Multiple Sclerosis Society. Fampridine, the first in a new family of medicines designed to restore proper nerve signals after myelin is lost, was tested in 25-foot timed walks.

    The improvement patients saw with Fampridine “was numerically quite small, and the average time to complete the 25 foot walk was not different between the treatment groups in either study,” said Eric Bastings, deputy director of the FDA’s Division of Neurology Products, in a memo to the panel. “For these reasons, it appears that the clinical meaning of the differences seen on the primary outcomes is in question.”

    Acorda is racing European drugmakers Merck KGaA and Novartis AG to introduce the first pill for MS. Current treatments, led by Teva Pharmaceutical Industries Ltd.’s Copaxone and Biogen Idec Inc.’s Avonex, are shots that reduce relapses and prevent symptoms of the disease from getting worse.

    MS worsens as damage to myelin causes muscle weakness, trouble with coordination and critical thinking, and memory loss. Women are at least twice as likely as men to get MS.

    “There might be someone using a walker or cane who finds it difficult to get from the kitchen to the bedroom, and Fampridine could make it easier,” said Howard Weiner, director of the Partners Multiple Sclerosis Center at Brigham & Women’s Hospital in Boston, in a phone interview before the FDA documents were released.

    Timed Walking Test

    A timed walking test is a logical way to measure the effectiveness of fampridine because there is a “physiologic” connection between the walking ability and the progression of the disease, Weiner said.

    The FDA said on May 6 it would review Fampridine under an expedited “priority review” program to speed clearance of novel medicines for serious illnesses. A drug awarded priority review is supposed to be decided on within six months, four months quicker than the review process for most medicines. Acorda in May said it anticipated an approval decision from the agency by Oct. 22.

    Ron Cohen, Acorda’s founder and chief executive officer, said he didn’t ask for a quick review of Fampridine. Transparency is critical for investors in the unprofitable biotech company, and Cohen said he was worried the application might get held up if it was taken out of normal review channels.

    ‘Delays Not Good’

    “To the extent that there are delays, or there are uncertainties in the process, that’s not a good thing because the last thing an investor wants to see is uncertainty,” Cohen said in an Aug. 18 phone interview.

    Development of Fampridine was started by Dublin-based Elan Corp. in the 1990s and later licensed by Acorda. The drug is a sustained-release form of 4-aminopyridine, which some MS patients now get from compounding pharmacies with a doctor’s prescription. These medicines are custom made for patients and overdoses can cause seizures and other side effects.

    Fampridine helped 35 percent of MS patients walk faster in a study whose results were reported in February. The drug’s ability to restore nerve signals after myelin is lost suggests it may also reduce other symptoms of the disease, regardless of what other medicines patients are taking, said John Richert, executive vice president of research and clinical programs for the New York-based National Multiple Sclerosis Society.

    ‘Theoretic Potential’

    “Potentially, it could be tried in the large majority of people with MS,” Richert said in an Oct. 7 phone interview. “It has at least the theoretic potential for being able to help with virtually any MS symptom.”

    Elan will manufacture Fampridine if it is approved and receive royalties on sales. The drug is the first that Acorda has submitted to the FDA. The company also sells Zanaflex capsules, a treatment for spastic muscles that it acquired from Elan in 2004.

    Cambridge, Massachusetts-based Biogen agreed in July to pay as much as $510 million for rights to market Fampridine outside the U.S. after Acorda said it wouldn’t be able to operate beyond next year without a partner.

    German drugmaker Merck asked the FDA last month to approve cladribine tablets to reduce relapses of MS. Novartis, of Basel, Switzerland, plans to submit its experimental pill, FTY720, to U.S. regulators by the end of the year to reduce relapse and progression of disability. Paris-based Sanofi-Aventis SA is also in late stages of testing its teriflunomide pill for MS.

    “Patients tell us they’re desperate for an oral drug,” Richert, of the MS Society, said. “We know that some people don’t go on medication in the first place because they can’t stand the thought of injection.”

    Source: Bloomberg.com © Bloomberg L.P. (09/10/09)

    Fampridine-SR likely to receive FDA approval with REMS/black box label

    Acorda LogoAcorda Therapeutics’ Fampridine-SR, a drug that is designed to improve walking ability in patients with multiple sclerosis, will likely receive FDA approval later this month, despite its increased risk for seizures, neurologists and a source close to the situation told Pharmawire.

    FDA briefing documents will be available on 12 October. The company is expecting an FDA decision on 22 October.

    But according to risk management consultants who previously worked at the FDA, the drug will likely receive a strict risk management (REMS) procedure and a black box warning for seizure risk.

    Patients with multiple sclerosis will ultimately face difficulties with walking, as their disease progresses. In clinical trials, Fampridine-SR has been found to improve impulse conduction in nerve fibres in which the insulating layer, called myelin, has been damaged.

    Repeated calls to Acorda were not returned.

    Fampridine-SR (4-AP) is an investigational oral, sustained-release tablet formulation of 4-aminopyridine, which is available in compounding pharmacies. A compounding pharmacy makes drugs from ingredients that physicians prescribe, but are not regulated by the FDA from a safety standpoint. There have been cases of accidental compounding error, which has lead to seizure and hospitalization in certain patients on 4-AP.

    A key criticism of Acorda’s drug is that less than half of the patients actually respond. In the first Phase III trial, there was a 25% improvement in walking speed after 14 weeks in 34.8% of patients taking Fampridine-SR compared to 8.3% on placebo.

    A source, who has been involved with the drug’s development since its initial stages at Elan  a number of years ago, said although a few patients respond to this drug, there have been individuals that demonstrated dramatic responses, which have encouraged further development of the agent. The source further noted that pilot studies at Elan sought to determine which patients would respond, but response proved difficult to predict.

    Neurologists and investigators have pushed for continued development of Fampridine-SR in order to standardize the formulation of a drug that has been sometimes shown to improve walking ability, according to the source. ”We would prefer to have 4-AP formulated correctly because if patients have a seizure, at least you know it wasn’t because of a local compounding pharmacy error,” he said.

    But there will need to be a lot of patient education with Fampridine-SR to prevent patients from overdosing, since the seizures are dose-dependent, the source added. Although he has not run into any problems so far in terms of seizures with 4-AP, he noted that he only has a small number of patients on this agent.

    Dr David Brandes, medical director of the Northridge Multiple Sclerosis Center and assistant clinical professor of neurology at UCLA, who has been using 4-AP in patients for 20 years, said there have been some seizures in Acorda’s trials, and one overdose that led to brain damage. While seizures are certainly a risk, it is not one that neurologists are afraid of, he said. The benefit is so great and this is a low dose of Fampridine, so the risk is remote, he noted.

    Dr Daniel Kantor, assistant professor of neurology and Director of the Comprehensive Multiple Sclerosis Center at the University of Florida, said he believes Fampridine-SR will definitely be approved with a REMS, and probably receive a boxed warning for seizure risk. The key issue now is on adoption, and if neurologists will choose to switch patients who are currently on 4-AP onto Acorda’s formulated drug, or just prescribe it to new patients.

    Kantor, who has prescribed 4-AP to a number of his patients on a selective basis, said after two months, patients will know whether or not they are a responder. The drug may make the most sense in patients who are heat-sensitive, since 4-AP helps the conduction of the nerves work better. From his experience, the response rate so far in his clinic has been much more than one-third of his patients. “I don’t know exactly how many, but at least half. I’m very happy with it. I’m not starting everyone on it, but I’m choosing who I’m starting on,” he said.


    Pricing will be key to adoption

    One main issue in terms of adoption, will ultimately be pricing, since the active ingredient in Fampridine-SR, the compounded agent 4-AP is much cheaper, neurologists noted. “Fampridine-SR is probably going to cost USD 10,000/year, since there’s no competition or pricing war, until Sanofi comes out with their competing agent, nerispirdine,” Kantor said.

    Acorda management have not stated an official price for Fampridine-SR yet, but industry analysts have modeled potential pricing in the range of USD 7000-10,000 annually. “Patients will have to pay a lot less from the compounding pharmacy, since 4-AP costs USD 70 per month. That’s USD 840 a year, versus paying USD 10,000,” Kantor said.

    Sanofi-Aventis’ nerispirdine, a drug that potentially helps improve walking ability in MS patients, is currently in Phase II trials, according to clinicaltrials.gov. Kantor said Sanofi is currently in the process of recruiting patients for their Phase III nerispirdine trials, and is in the process of adding additional clinical sites.

    Patients with heat sensitivity - or Uhthoff’s phenomenon - may benefit the most from Fampridine-SR, noted Dr Robert Lisak, chairman of neurology at Wayne State University School of Medicine and an investigator on the trial. Uhthoff’s phenomenon, which is common, is the appearance or worsening of neurological symptoms when body heat is elevated.

    Dr Michael Racke, professor and chairman of neurology at the Ohio State University Medical Center, said the agent creates a selective advantage for conduction along demyelinated neurons, so physicians would use oculography to diagnose patient improvements on double vision. However, most physicians won’t have this test as a resource, he said.

    The neurology community is optimistic for approval but there are price concerns, Lisak said. Dr David Mattson, professor of neurology and vice chairman for clinical practice at Indiana University School of Medicine, agreed that he was optimistic for the agent’s approval.

    Cost concerns remain since the safety data on Fampridine-SR compared to 4-AP has never been confirmed in a clinical, head-to-head study, Lisak said. Those patients with significant deficits, but who are still ambulatory and looking to walk faster, are likely candidates for Fampridine-SR, Lisak speculated. The agent has potential in selected patients, he added.


    REMS procedure

    A REMS consultant, who previously worked at the FDA, said Biogen Idec’s and Elan’s risk management program for its leading multiple sclerosis drug Tysabri is the example the FDA uses as the gold standard for REMS. Biogen has obtained ex-US rights to Fampridine-SR and Elan receives seven percent of royalties on the drug.

    To minimize the number of seizures that may occur with Fampridine-SR, the company may need to have patient specific procedures in place to prevent things like overdose, a second REMS consultant noted.

    The REMS procedure will have to be extremely vigilant about warning patients regarding overdose; the therapeutic window is narrow, and seizures are dose dependent, one industry observer noted. Insurance companies may also ask for proof of response. The onus will be on neurologists to explain the risks of overdose to their patients - which may make it more difficult to sell the drug, and ultimately hurt sales, he said.

    Dr Norman Kachuck, chief of the Multiple Sclerosis and Neuroimmunology Division of the Department of Neurology, and Director of the University of Southern California MS Comprehensive Care Center, noted that there are an overwhelming number of patients who have symptoms that could be remediated with Fampridine-SR. It will require a receptive neurologist and an efficient patient relationship to determine who is responding to the agent, he said.

    Dr Hillel Panitch, a primary investigator for Acorda and professor of neurology and director of the multiple sclerosis clinic at the University of Vermont College of Medicine and Fletcher Allen Health Care, said the agent has a place in people who have trouble walking with secondary progressive and primary progressive MS with spastic paralysis. “I’ve been following this for a while and I am glad to see someone finally has a good enough result for approval,” he said.

    Panitch said he would not treat everyone with Fampridine-SR, but would reserve the agent for patients with limited walking, spasticity and weakness. It will be a useful addition for patients who could use an extra boost to leg strength and walking ability. Some patients have had remarkable responses, Panitch agreed, adding that the agent can make a big difference.

    Source: The Finacial Times © The Financial Times Ltd 2009 (03/10/09)

    Retention rates and safety from two phase 3 Fampridine-SR extension studies released

    Acorda LogoData from two long-term open-label extension studies of Fampridine-SR show that 86.0% of participants remained on therapy after a maximum treatment time of 15 months in study MS-F204EXT, and 69.5% remained on therapy after a maximum treatment time of 36 months in study MS-F203EXT. The average treatment time for all patients was 10 months in the MS-F204EXT study and 26 months in the MS-F203EXT study, both inclusive of dropouts. The EFNS poster presentation inadvertently reported maximum treatment times for both studies as the median treatment times. The types of adverse events reported in the two extensions studies were consistent with the expected adverse event profile in people with more advanced multiple sclerosis (MS) and were similar between the two studies. These extension studies followed double-blind, placebo-controlled Phase 3 studies of Fampridine-SR, MS-F203 and MS-F204, in people with MS to improve walking ability.

    The data were presented on Sunday, September 13th at the 13th Congress of the European Federation of Neurological Societies (EFNS) in Florence, Italy. Additional safety and efficacy data from the MS-F203 extension study were presented on September 10th at the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

    The cut-off date for the EFNS analysis was November 30, 2008, which was the cut-off for the analyses used in Acorda's New Drug Application (NDA) filing for Fampridine-SR earlier this year. As of this date, the approximate total exposure to Fampridine-SR was 565 patient-years in the MS-F203 extension study and 193 patient-years in the MS-F204 extension study.

    In the MS-F203 extension study, there were 82 discontinuations (30.5%), 28 of which were due to adverse events (10.4%). There were 30 discontinuations (14.0%) in the MS-F204 extension study, four of which were due to adverse events (1.9%).

    The most commonly reported adverse events in the MS-F203 extension study were: urinary tract infection (34.6%), MS relapse (31.2%), fall (29.7%), arthralgia (16.4%) and asthenia (16.0%). The most common adverse events in the MS-F204 extension study were: fall (26.2%), urinary tract infection (20.6%), MS relapse (18.7%), asthenia (9.3%) and balance disorder (9.3%). Serious adverse events occurred in 23.4% of participants in the MS-F203 extension study and 7.9% of participants in the MS-F204 extension study. The most frequent serious adverse event in both studies was MS relapse (4.1% in the MS-F203 extension study and 1.9% in the MS-F204 extension study).

    There were four seizure-related events reported in the MS-F203 extension study at the 10 mg twice daily dose, consisting of one complex partial seizure and three patients with convulsion. There were no seizure-related events reported in the MS-F204 extension study. The incidence of seizure at the 10 mg twice daily dose from a pooled analysis of all three ongoing extension studies of Fampridine-SR, including MS-F202EXT, MS-F203EXT and MS-F204EXT, was 0.41 per 100 patient-years. The expected incidence of first seizure in the general MS population is approximately 0.35 (± 0.15) per 100 patient-years1.

    Trial Design

    All participants who had completed the Phase 3 placebo-controlled trial were eligible to enroll in the extension study of their respective trial; 269 participants of the MS-F203 trial and 214 participants of the MS-F204 trial elected to enroll. All participants in the extension studies were treated with Fampridine-SR at 10 mg twice daily, including participants who received placebo during the placebo-controlled trial. Baseline demographics of the participants of both studies were similar. More than half of the study participants in the MS-F203 and MS-F204 extension studies were diagnosed with secondary-progressive MS (52.8% and 50.0% respectively), with the remainder of diagnosed with relapsing-remitting MS (28.6% and 34.6% respectively), primary-progressive MS (14.9% and 11.2% respectively) or progressive relapsing MS (3.7% and 4.2% respectively).

    Source: Medical News Today © 2009 MediLexicon International Ltd (18/09/09)

    Fampridine-SR, Acorda's Multiple Sclerosis drug improves walking speed over 2 yrs

    Acorda LogoAcorda Therapeutics Inc said interim analysis of a late-stage trial of its experimental multiple sclerosis treatment, Fampridine-SR, showed that the drug improved walking speed in patients over a two-year period.

    A total of 66 patients, or 24.9 percent of study participants, saw an average improvement of more than 30 percent in walking speed after 12 months of treatment and 22 percent after 24 months.

    Fampridine-SR is an oral, sustained-release drug designed to improve walking ability in people with multiple sclerosis.

    There were four seizure-related events reported in the trial, including one complex partial seizure and three patients with convulsion, the company said in a statement.

    "This implies a seizure rate of 1.5 percent, which is in line with what would be expected from the general multiple sclerosis population," J.P. Morgan analyst Geoffrey Meacham said in a note.

    It would have been great to see no seizures in the study, but this would be an unrealistic expectation for any multiple sclerosis study since multiple sclerosis predisposes to seizure risk, Meacham added.

    He also said that apart from the seizure data, the safety profile for the drug, also known as MS-F203, looked clean and overall the data supports a regulatory approval.

    Acorda shares the marketing rights to Fampridine with Biogen Idec Inc, who acquired the rights to the drug outside the United States for an upfront payment of $110 million in July.

    Hawthorne, New York-based Acorda is entitled to receive up to $400 million more if the drug meets certain regulatory and sales milestones.

    Source: Reuters © Thomson Reuters 2009 (11/09/09)

    Date of FDA advisory committee review of Fampridine-SR for improvement of walking ability in people with MS announced

    Acorda LogoAcorda Therapeutics, Inc. today announced that the U.S. Food and Drug Administration (FDA) has confirmed that its Peripheral and Central Nervous System Drugs Advisory Committee will review the Company’s New Drug Application (NDA) for Fampridine-SR on October 14, 2009.

    The Company also announced that it has received preliminary approval for the proposed trade name Amaya from the FDA.

    Fampridine-SR is a novel therapy being studied as a potential treatment to improve walking ability in people with multiple sclerosis. The Fampridine-SR NDA was accepted by the FDA on May 5, 2009 and assigned Priority Review status. At that time, the FDA set a Prescription Drug User Fee Act (PDUFA) date of October 22, 2009; the PDUFA date is the target date for the FDA to complete its review of Fampridine-SR.

    About Fampridine-SR

    Fampridine-SR is a sustained-release tablet formulation of the investigational drug fampridine (4-aminopyridine or 4-AP). In laboratory studies, fampridine has been found to improve impulse conduction in nerve fibers in which the insulating layer, called myelin, has been damaged. Fampridine-SR is being developed by Acorda Therapeutics and manufactured by Elan Corporation plc.

    Source: Source: Acorda Therapeutics, Inc. (25/08/09)

    Biogen gains overseas rights to Acorda's MS drug Fampridine-SR

    Acorda Logo

    Biogen Idec Inc has acquired rights outside the United States to Acorda Therapeutics Inc's experimental multiple sclerosis drug, the companies said on Wednesday.

    Biogen, which makes the multiple sclerosis drugs Avonex and Tysabri, will pay Acorda $110 million up front for rights to Fampridine-SR. It could also pay up to $400 million more if the drug meets certain regulatory and sales milestones.

    Cambridge, Massachusetts-based Biogen will make tiered, double-digit royalty payments to Acorda on overseas sales of Fampridine-SR, which is an oral, sustained release drug designed to improve walking ability in people with multiple sclerosis.

    Acorda maintains rights to the drug in the United States, where the medicine is under review by regulators and a decision is expected by Oct. 22. The company has not yet submitted a European application for the drug.

    Acorda will pay 7 percent of the upfront and milestone payments it receives from Biogen to Irish drugmaker Elan Corp (ELN.I), which manufactures Fampridine-SR.

    Fampridine, if approved, would broaden Biogen's MS franchise as the company battles to boost sales of Tysabri, which have been curtailed amid concerns over its association with a potentially deadly brain infection.

    Source: Reuters © Thomson Reuters 2009 (01/07/09)

    Acorda Multiple Sclerosis drug eligible for coordinated review in Europe

    Acorda Logo

    Acorda Therapeutics Inc. said that its new multiple sclerosis drug is eligible for a centralized regulatory review in Europe, potentially opening up huge new markets for the medication if it receives approval.

    The Hawthorne-based biotech company has been seeking approvals for the drug, known as Fampridine-SR, after a study showed that patients taking the medication walked faster than patients taking a placebo.

    Multiple sclerosis is a chronic nervous-system disease in which the immune system attacks nerve fibers in the brain and spinal cord. If the drug is approved, the drug could one day make walking easier for the multiple sclerosis victims who deal with mobility problems.

    Acorda said that European regulators have decided that the drug can be evaluated in a single, coordinated review on behalf of all European Union member countries, instead of the time consuming process of each country doing the evaluation seperately. Acorda could gain a 10-year market exclusivity for Fampridine-SR in European Union countries under the approval process.

    Acorda is also seeking approval to market the drug in the United States from the U.S. Food and Drug Administration.

    Source: LoHud.com ©2009 The Journal News (09/06/09)

    FDA accepts Fampridine-SR new drug application for filing

    Acorda Logo

    Acorda Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted the Fampridine-SR New Drug Application (NDA) for filing, assigning Priority Review and a Prescription Drug User Fee Act (PDUFA) date of October 22, 2009. The PDUFA date is the target date for the FDA to complete its review of the Fampridine-SR NDA.

    “I am pleased that we were able to work quickly to address the comments from the FDA and resubmit our NDA approximately three weeks from having received the Refuse to File letter on our initial NDA submission, and that the FDA accepted the filing less than two weeks later,” said Ron Cohen, M.D., Acorda Therapeutics’ President and CEO. “We are also encouraged that the FDA has elected to assign Priority Review status to the Fampridine-SR NDA.”

    About Fampridine-SR
    Fampridine-SR is a sustained-release tablet formulation of the investigational drug fampridine (4-aminopyridine or 4-AP). In laboratory studies, fampridine has been found to improve impulse conduction in nerve fibers in which the insulating layer, called myelin, has been damaged. Fampridine-SR is being developed by Acorda Therapeutics and manufactured by Elan Corporation plc.

    Source: Acorda Therapeutics, Inc (07/05/09)

    Acorda Therapeutics resubmits new drug application for Fampridine-SR in Multiple Sclerosis

    Acorda Logo

    Acorda Therapeutics, Inc. announced the resubmission of its New Drug Application (NDA) for Fampridine-SR to the U.S. Food and Drug Administration (FDA). Fampridine-SR is a novel therapy being developed to improve walking ability in people with multiple sclerosis (MS).

    Acorda received a Refuse to File (RTF) letter for the Fampridine-SR NDA on March 30, 2009, which cited the need to correct "format issues" and requested additional supporting information before the NDA could be accepted for review.

    Based on subsequent discussions with the FDA, Acorda has resubmitted the Fampridine-SR NDA and believes that all of the Agency's comments related to the RTF have been addressed.

    Source: Medical News Today © 2009 MediLexicon International Ltd (27/04/09)

    Acorda says FDA seeks additional data on NDA for multiple sclerosis drug

    Acorda Logo
    Biotechnology company Acorda Therapeutics, Inc. revealed that it received a "refuse to file letter" from the U.S. Food and Drug Administration, or FDA, pertaining to its New Drug Application, or NDA, for Fampridine-SR, a new therapy under development for improving the walking ability in people suffering from multiple sclerosis.

    The Hawthorne, New York-based company said that the FDA has raised "format issues" concerning its electronic submission, and has called for the reformatting of some of the data in the NDA. The agency has also asked for some additional supporting information.

    The company, however, noted that the FDA has not requested or recommended additional clinical or other studies. The company said it will seek a meeting with the FDA at the earliest to discuss its comments on the NDA filing.

    As per the FDA web site, incomplete NDAs become the subject of a formal refuse-to-file action, with the applicant receiving a letter detailing the decision and the deficiencies that form its basis. This decision must be forwarded within 60 calendar days after the NDA is initially received by CDER.

    Source: RTT News © 2009 RTTNews (31/03/09)

    Fampridine boosts mobility in multiple sclerosis

    Acorda Logo

    An experimental drug called Fampridine improves walking ability in some patients with multiple sclerosis (MS), a disease of the nervous system that crimps mobility, a study published in The Lancet says.

    Doctors recruited 301 adults with MS in the United States and Canada, and gave the drug to 229 of the recruits and a dummy lookalike pill, also called a placebo, to 72 others.

    Of those who received the drug, just over a third experienced an increase in the speed at which they could walk 25 feet (7.69 metres). The boost in speed was around 25 percent.

    Of those who took the placebo, around eight percent had an increase in speed.

    The drug was apparently well tolerated. Only 11 people, or less than five percent, of those in Fampridine group dropped out of the 14-week trial because of side effects.

    "This study indicates that Fampridine could represent an important new way to treat multiple sclerosis and perhaps become the first drug to improve certain symptoms of the disease," lead researcher Andrew Goodman, a neurologist at the University of Rochester Medical Center in New York, said in a press release.

    "The data suggest that, for a sub-set of MS patients, nervous system function is partially restored while taking the drug."

    Around a million people around the world are affected by MS, a degenerative disease in which the immune system attacks myelin, the fatty sheath that protects nerve fibres.

    As a result, signals between nerve cells are delayed, disrupted or even blocked, rather like a poor connection in an electrical wire, and this causes worsening problems in coordination and balance, as well as blurred vision and slurred speech.

    Current drugs for MS suppress the immune system. They can be useful for slowing progression of the disease, but cannot improve impaired function.

    Fampridine does not address the problem of myelin loss. Instead, it is believed to work by blocking channels for potassium ions on the surface of nerve cells.

    These channels act rather like gates, and help to regulate electrical impulses.

    The study was the final stage in a three-phase process of clinical trials to assess new drugs for safety and effectively.

    Fampridine's developer, Acorda Therapeutics, Inc., this month submitted a licence application to the the US watchdog, the Food and Drug Administration (FDA), the press release said.

    Source: AFP © 2009 AFP.(27/02/09)

    New drug application for Fampridine-SR for improvement of walking ability in people with Multiple Sclerosis submitted

    Acorda Logo

    Acorda Therapeutics, Inc. announced the submission of a New Drug Application to the U.S. Food and Drug Administration (FDA) on January 30, 2009 for Fampridine-SR, a novel therapy being developed to improve walking ability in people with multiple sclerosis (MS). The Company expects that the NDA filing, if accepted, will be subject to standard review, which would provide a target for the FDA to complete its review within ten months from receipt of the submission.

    “This NDA filing is a major milestone for Acorda and our Fampridine-SR development program,” said Acorda Therapeutics President and CEO Ron Cohen, M.D. “Walking impairment is one of the most pervasive and alarming aspects of MS for patients, their families and their health care providers. There are no medicines currently indicated to improve walking ability in people with MS, and Fampridine-SR therefore may represent an important new approach to MS therapy. We are excited to have taken this major step toward potentially making Fampridine-SR available to help people with MS.”

    Approximately 400,000-500,000 people in the Unites States have MS, and recent studies indicate that between 64-85% of people with MS have walking disability 1,2. Fully 70% of people with MS who have walking disability report it to be the most challenging aspect of their disease1.

    The Fampridine-SR NDA submission is based on data from a comprehensive development program assessing the safety and efficacy of Fampridine-SR, including two Phase 3 trials that involved 540 people with MS and were conducted under Special Protocol Assessments (SPAs) from the FDA. The safety and efficacy profile of Fampridine-SR was consistent across Phase 2 and Phase 3 trials. Overall, the NDA filing included more that 50 clinical studies of Fampridine-SR. The total exposure to Fampridine-SR in MS studies filed as part of the NDA was over 1,200 patient-years. Additionally, more than 450 people are currently enrolled in Fampridine-SR extension trials, with treatment duration ranging from seven months to almost five years.

    The Company also has discussed Fampridine-SR with regulatory authorities in Europe and believes that the current data are sufficient to file a centralized Marketing Authorization Application (MAA) with the European Medicines Agency (EMEA). The Company plans to file the MAA when it has determined the commercialization pathway that maximizes the value of Fampridine-SR outside the U.S.

    1 Harris Interactive poll, April 2008

    2 NARCOMS patient database

    Source: Acorda Therapeutics (01/02/09)

    Additional data released for second Phase III clinical trial of Fampridine-SR on walking ability in people with multiple sclerosis

    Acorda Logo

    Acorda Therapeutics has announced additional data from its second Phase III clinical trial of Fampridine-SR on walking ability in people with multiple sclerosis.

    Previously, the company announced the trial met its primary endpoint with a significantly greater proportion of people taking Fampridine-SR having a consistent improvement in walking speed compared to people taking placebo (42.9% versus. 9.3%), as measured by the Timed 25-Foot Walk (p<0.001).

    The study also met its secondary outcome measure, leg strength, showing a statistically significant increase in the Fampridine-SR Timed Walk responders compared to placebo (p=0.028).

    The response rate for Fampridine-SR treated patients was higher than placebo across all multiple sclerosis (MS) subtypes. Response rates for the four major MS subtypes in the study were - relapsing-remitting: 37.2%; secondary-progressive: 45.9%; primary-progressive: 50%; and progressive-remitting: 40%. Response rates were similar between study participants who were being treated with immunomodulators and those who were not.

    The Fampridine-SR treated group showed improvement in the Ashworth Score (a physician-reported measure of spasticity), which was significant in an unplanned analysis. Baseline demographic and disease characteristics of study participants were also presented, including the percentage of Fampridine-SR treated patients with each subtype of MS (relapsing-remitting: 35.8%; primary-progressive: 8.3%; secondary-progressive: 51.7%; and progressive-relapsing: 4.2%) and the mean duration of disease in Fampridine-SR treatment patients (14.43 years).

    Andrew Goodman, director of the Multiple Sclerosis Center at the University of Rochester, said: "People with MS often cite walking disability as one of the most challenging aspects of their disease, and there are no therapies currently indicated for improving walking in MS. The results of this study, which were consistent with the first Phase III Fampridine-SR trial, show that Fampridine-SR may provide benefit to people with walking difficulties."

    Source: TradingMarkets.com © 2008 The Connors Group, Inc. (23/09/08)

    Dose comparison trial of sustained-release fampridine in multiple sclerosis

    Axons

    OBJECTIVE: To examine the efficacy and safety of three different doses of sustained-release fampridine in people with multiple sclerosis (MS).

    METHOD: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study recruited 206 participants at 24 centers in the United States and Canada. After a single-blind, 2-week placebo run-in, participants were randomly assigned to receive fampridine (10, 15, or 20 mg twice daily) or placebo for 15 weeks. The primary efficacy variable was percent change in walking speed based on the timed 25-foot walk.

    RESULTS: Trends for increased walking speed were consistent across dose groups vs placebo, but not significant, on the prospective analysis. An increase from baseline in lower extremity strength during the 12-week stable-dose period was seen in the groups receiving 10- and 15-mg doses, compared with placebo (p = 0.018 and 0.003). There were no significant changes in other secondary assessments. Post hoc analysis revealed subsets of participants in each dose group with walking speeds during the treatment period that were consistently faster than during the nontreatment period. There were significantly more "consistent responders" in the drug-treated groups than in the placebo group (36.7% compared with 8.5%). Consistent responders showed significantly greater improvement in self-assessed ambulation on the 12-Item MS Walking Scale than did nonresponders. Fampridine was generally well tolerated. Severe and serious adverse events were more frequent at the highest dose.

    CONCLUSIONS: This phase 2 study suggests that a subgroup of patients, when treated with fampridine, experiences a clinically relevant improvement in walking ability, which is sustained for at least 14 weeks.

    Goodman AD, Brown TR, Cohen JA, Krupp LB, Schapiro R, Schwid SR, Cohen R, Marinucci LN, Blight AR; For the Fampridine MS-F202 Study Group.
    From the Department of Neurology (A.D.G., S.R.S.), University of Rochester, NY; Department of Neurology (T.R.B.), Evergreen Hospital Medical Center, Seattle, WA; Department of Neurology (J.A.C.), Cleveland Clinic Foundation, OH; Department of Neurology (L.K.), Stony Brook University Hospital, NY; Minneapolis Clinic of Neurology (R.S.), MN; and Acorda Therapeutics, Inc. (R.C., L.N.M., A.R.B.), Hawthorne, NY.

    Source: Pubmed PMID: 18672472 (12/08/08)

    Positive phase III results for multiple-sclerosis drug Fampridine-SR announced

    Acorda Therapeutics Inc. announced positive results for the second Phase III clinical trial for its drug Fampridine-SR, used in the treatment of multiple sclerosis.

    The company said a significantly greater proportion of people taking the drug saw an improvement in their walking speed compared to people taking a placebo.

    The company said based on the positive results of the Phase III trials, it will submit a new drug application to the U.S. Food and Drug Administration in the first quarter of 2009. Acorda said it plans to request a priority review.

    Source: Trading Markets.com © Thomson Financial News Limited 2008 (02/06/08)

    Acorda Says Drug Study Is Successful

    Shares of Acorda Therapeutics Inc. soared in premarket trading Monday after the biotechnology company said a study showed its experimental multiple sclerosis drug Fampridine-SR does not raise the risk for certain heart-related side effects.

    Fampridine-SR is currently being studied in a late-stage clinical trial to evaluate its safety and effectiveness in improving walking ability in people with multiple sclerosis.

    The study, whose results were being announced Monday, evaluated the drug's potential to cause an increase in what is called the QT interval. A rise in this heart-related measure may signify a higher risk of developing an abnormal heart rhythm.

    According to the study's results, Fampridine-SR was found to be no different than placebo.

    The U.S. Food and Drug Administration requires thorough QT studies for all new drugs seeking regulatory approval, Acorda said.

    The QT trial compared the effects of Fampridine-SR, given at 10 milligrams twice daily and 30 milligrams twice daily, with placebo and moxifloxacin in 208 healthy subjects. Moxifloxacin is known to increase the QT interval.

    "We are delighted with the results of this QT study, and are looking forward to completing our second Phase 3 trial of Fampridine-SR in multiple sclerosis patients in the second quarter of this year," Acorda President and Chief Executive Ron Cohen said.

    Source: Forbes.com © 2008 Forbes.com LLC™

    Drug gives MS patient more independence
    A new treatment for multiple sclerosis is showing great promise.

    A Capital Region woman who is proof positive of it's potential.

    It's been 28 years since Chris Nigro was diagnosed with MS. Of the four types of MS, he has secondary progressive -- meaning the condition generally keeps getting worse. She was told there was no treatment, but she never gave up hope of walking.

    Then Nigro began treatment at the Multiple Sclerosis Center of Northeastern New York and her condition not only stabilized, but she began to grow stronger thanks to new medications.

    Nigro's improvements made her a prime candidate to take part in a study for a drug called Fampridine.

    "For years I had been trying to take one step when I pulled myself on a bar and I always felt if I could take one step, then I can try for two steps and then you can try for three and then you're off," she said.

    Now she's able to walk about 50 feet with a rolling walker.

    "Just to put one foot in front of the other and put my weight on my legs just feels wonderful to me," she said.

    For the first time in 14 years her sister Nora Reid sees her upright.

    "It's just so amazing and wonderful to see her on her feet. And she's taller than I am and I haven't seen that in along time," Reid said.

    Fampridine is an old drug with a new life.

    "It doesn't alter the disease, but it helps people function better," explained Dr. Keith Edwards, a neurologist at the MS Center.

    Nigro is among 500 people nationwide who took part in the most recent clinical trial. While she didn't know what she was getting, it was clear she was getting better.

    "It's symptomatic treatment to allow the messages to get through the spinal cord better," Edwards said.

    The study recently wrapped up. Because Nigro is still being followed she's able to get the drug free of charge.

    "I don't know that she's going to run the 100 yards in under 10 seconds but her independence is going to continue to improve," Edwards said.

    Fampridine, which is taken in pill form, remains under study and the results are still being compiled. So it's not clear it will work for every MS patient like Nigro.

    Also, because it's still under review, Edwards can only say it appears the drug worked for her. He also points out MS treatment is not one size fits all.

    Source: wnyt.com © Copyright 2008 WNYT-TV, LLC (24/01/08)

    Acorda Therapeutics Completes Enrollment of Phase 3 Clinical Trial of Fampridine-SR

    Acorda Therapeutics, Inc. announced today that it has completed enrollment for its Phase 3 clinical trial of Fampridine-SR in multiple sclerosis (MS).

    The trial is designed to evaluate the safety and efficacy of Fampridine-SR in improving walking ability in people with MS. 240 patients were enrolled at 39 clinical trial sites in the United States and Canada. The Company expects data from the trial in the second quarter of 2008.

    Source: Acorda Therapeutics, Inc. (03/12/07)

    Acorda Therapeutics Begins Second Phase 3 Clinical Trial of Fampridine-SR in Multiple Sclerosis
    Acorda Therapeutics announced today that it has begun a second Phase 3 clinical study of Fampridine-SR in multiple sclerosis (MS), with the randomisation of its first patient into the treatment phase of the study. The study is expected to enroll approximately 200 patients at 35 leading MS clinical centres in the United States and Canada. Fifteen centres have been initiated and are in the process of screening subjects for the trial.

    The MS-F204 study, which is conducted under a Special Protocol Assessment (SPA) issued by the Food and Drug Administration (FDA), will evaluate the safety and efficacy of Fampridine-SR in improving walking ability in people with MS. An SPA is a process in which the FDA provides guidance on a Phase 3 clinical trial whose data will form the primary basis for an efficacy claim. Pending clinical results from MS-F204, FDA has agreed that this study together with the previous Phase 3 study would be adequate to support a New Drug Application (NDA) for Fampridine-SR.

    The primary outcome measure for the study will be a walking response criterion, defined as a consistent improvement in walking speed as measured by the Timed 25-Foot Walk. The secondary outcome measure for this study is the Lower Extremity Manual Muscle Test (LEMMT).

    "As a clinician I see how impaired walking affects my patient's ability to conduct even the most routine tasks," said Lauren Krupp, M.D., Professor of Neurology and Psychology, Stony Brook University. "A drug that could improve walking ability would be a significant contribution to the treatment of people with MS."

    Ron Cohen, M.D., President and CEO of Acorda Therapeutics, said, "Walking impairment in MS is pervasive and seriously debilitating in this patient population. We are proud to be working towards an important treatment that potentially may help to address this major unmet medical need."

    Source: Acorda Therapeutics (07/06/07)

    Acorda Therapeutics Presents Fampridine-SR Data at ACTRIMS Meeting
    Data Validates Clinical Meaningfulness of Timed Walk Response.

    Acorda Therapeutics, Inc.® today announced that the Company presented a "meta-analysis" or combined analysis of two clinical trials of Fampridine-SR in multiple sclerosis during a poster session at the Americas Committee for Treatment and Research in MS (ACTRIMS) Meeting in Washington, D.C. on Saturday, June 2, 2007. The poster, "Validation of Consistent Improvement in Walking Speed on the Timed 25 Foot Walk as a Measure of Clinically Meaningful Change," was presented by Andrew Goodman, M.D., Director of the Multiple Sclerosis Center at the University of Rochester.

    The objective of the analysis was to validate a consistent response criterion as a measure of clinically meaningful change. A consistent timed walk responder was defined as a subject whose walking speeds for at least three of the four on-treatment visits were faster than the fastest speed across any of their five non-treatment visits. In both studies, Fampridine-SR treatment was associated with significantly increased probability of this response compared to placebo (p less than 0.001). Both clinical trials were double-blind, placebo-controlled, parallel group, multi-center studies. The analysis was designed after the data from the first study were available. A total of 501 patients were included in the analysis.

    The clinical meaningfulness of this response criterion was assessed primarily by use of the 12-Item MS Walking Scale (MSWS-12), a questionnaire in which the patient rates the clinical impact of his or her walking disability on activities of daily life. Additional criteria for clinical meaningfulness included a seven-point Subject Global Impression (SGI) and a seven-point Clinician Global Impression (CGI). In the meta-analysis, timed-walk responders had significantly greater average improvements from baseline in the MSWS-12 score than the non-responders in both studies individually (p=0.02 and p less than 0.001, respectively) and in the meta-analysis (p less than 0.001). In addition, average scores for all 12 individual questions in the MSWS-12 were better for timed walk responders in both studies.

    Timed walk responders also showed significantly better SGI scores than non-responders in the meta-analysis (p less than 0.001) and in both studies individually (p=0.004 and p less than 0.001, respectively). The CGI was applied differently in the two studies, so the meta-analysis was not performed. It showed a strong trend in the retrospective analysis of the first trial (p=0.056) and significant improvement for responders versus non-responders in the second trial (p less than 0.001).

    The validation of the consistent timed walk response criterion was consistent across the studies as well as in the patient subgroups examined. The subgroups included patients with all of the four major types of MS course as well as patients with a wide range of disability at baseline.

    Andrew Goodman, M.D., Professor of Neurology, Chief, Neuroimmunology Unit, Director, Multiple Sclerosis Clinic at the University of Rochester Medical School said, "Walking impairment is one of the most common and critical problems for patients with MS, impacting a wide range of their activities. There are no therapies available today that are indicated for improving mobility in patients with MS. This meta-analysis found that the consistent improvement in walking speed on the Timed 25-Foot Walk represented clinically meaningful improvements for patients, as measured by three independent scales."

    About Fampridine-SR

    Fampridine-SR is a sustained-release tablet formulation of the investigational drug fampridine (4-aminopyridine, or 4-AP). Data collected in laboratory studies found that fampridine can improve the communication between damaged nerves, which may result in increased neurological function.

    Fampridine-SR Mechanism of Action

    A nerve cell has one extension, called an axon, which it uses to communicate via electrical signals to other nerve cells. All but the smallest axons have a special covering of a fatty substance called myelin that acts as insulation to preserve and speed these nerve signals, much like the insulating cover of an electrical cord helps preserve the transmission of electricity.

    In MS, the myelin becomes damaged and the axon cannot effectively transmit electrical impulses. Specifically, the damaged myelin exposes channels in the membrane of the axon, which allow potassium ions to leak from the axon, dissipating the electrical current. Fampridine-SR blocks these exposed channels, and helps the electrical signals to pass through areas of damage.

    Source: Acorda Therapeutics, Inc. (04/06/07)

    Acorda Therapeutics and FDA Reach Agreement on Special Protocol Assessment for Second Phase 3 Study of Fampridine-SR in Multiple Sclerosis
    Acorda Therapeutics, Inc. today announced that it has reached agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for a second Phase 3 trial of Fampridine-SR in Multiple Sclerosis (MS). An SPA is a process in which the FDA provides evaluation and guidance on clinical trial protocols for Phase 3 trials. The objective of the study is to show that individuals treated with Fampridine-SR are significantly more likely to have consistent improvements in their walking than those treated with placebo. Pending clinical results, the FDA has agreed that this trial, MS-F204, together with the company's first Phase 3 trial, MS-F203, would be adequate to support a New Drug Application (NDA) for Fampridine-SR.

    "We are pleased to have reached this agreement with the FDA, and are already working closely with our team of 35 MS centers to begin the study," said Ron Cohen, M.D., President and CEO. "Currently, there are no approved therapies that improve mobility in people with MS and physicians and patients regularly rate walking as one of the areas of greatest unmet medical need for this condition."

    MS-F204 Trial Design

    The primary outcome measure for the study will be a walking response, defined as a consistent improvement in walking speed as measured by the Timed 25-Foot Walk. Efficacy will be based solely on the achievement of statistical significance in the primary outcome measure. The secondary outcome measure for this study is the Lower Extremity Manual Muscle Test (LEMMT). Additional outcome measures, such as the Ashworth score for spasticity, a Clinician Global Impression and a Subject Global Impression, are included to allow an integrated efficacy analysis across studies. A visit at the conclusion of the study will provide pharmacodynamic information. Approximately 35 MS centers in the U.S. and Canada are expected to participate in the trial, and the trial is designed to enroll approximately 200 participants.

    The design of MS-F204 is fundamentally similar to Acorda's first Phase 3 trial of Fampridine-SR in MS, MS-F203. However, the current study protocol will require 14 weeks of patient participation compared to 21 weeks in MS-F203.

    About Fampridine-SR

    Fampridine-SR is a sustained-release tablet formulation of the investigational drug fampridine (4-aminopyridine, or 4-AP). Data collected in laboratory studies found that fampridine can improve the communication between damaged nerves, which may result in increased neurological function.

    Source: Acorda Therapeutics, Inc. (22/05/07)

    Acorda Therapeutics Presents Data from its Phase 3 Study of Fampridine-SR in Multiple Sclerosis at the American Academy of Neurology Meeting
    Acorda Therapeutics, Inc.® today presented data from a Phase 3 clinical trial of Fampridine-SR in people with multiple sclerosis (MS) at the American Academy of Neurology meeting. Andrew Goodman, M.D., Director of the Multiple Sclerosis Center at the University of Rochester, presented top-line results on walking ability, leg strength, spasticity and clinician and subject global impressions. Dr. Goodman also presented a review of safety data.

    Presentation Highlights

    The prospectively-designed analysis plan for the study was based on a responder criterion, defined as a consistent improvement in walking speed, as measured with the Timed 25 Foot Walk. A significantly greater proportion of people taking Fampridine-SR were Timed Walk Responders compared to people taking placebo (34.8 percent vs. 8.3 percent, p less than 0.0001). Increased response rate with treatment was seen across all four major (relapsing and progressive) types of MS.

    The mean increase in walking speed, compared to pre-treatment, for Fampridine-SR treated Timed Walk Responders was significantly greater at every visit during the treatment period, compared to both Fampridine-SR Timed Walk Non-Responders and placebo treated patients (p less than 0.0001). The average increase in walking speed over the treatment period, compared to baseline, was 25.2 percent for the drug treated Timed Walk Responders vs. 4.7 percent for the placebo group. In follow-up visits, at two and four weeks after the end of the treatment period, Responder and Non-responder groups returned to their baseline walking speeds.

    The clinical significance of the consistent response on the timed walk was validated in the trial primarily by the 12-Item Multiple Sclerosis Walking Scale (MSWS-12), a patient self-assessment of walking disability. There was a statistically significant improvement in the MSWS-12 score for walking Responders compared to Non-responders (p less than 0.001). In addition, the mean scores on all 12 questions in the MSWS-12 were better for the Responder group than the Non-responder group.

    Subject Global Impression and Clinician Global Impression scales were used as secondary validators of clinical meaningfulness. Both measures also showed statistically significant improvement among Responders compared to Non-responders (p = 0.0010 and p less than 0.0001, respectively).

    Statistically significant increases in leg strength, as measured by the Lower Extremity Manual Muscle Test (LEMMT), were seen in both the drug-treated Timed Walk Responders (p = 0.0002) and the drug-treated Non-responders (p = 0.046), compared to placebo-treated patients.

    In an unplanned, direct comparison of Fampridine-SR vs. placebo-treated groups, the following measures were significantly improved in the Fampridine-SR-treated group: mean change in walking speed (p = 0.0004), mean change in the Lower Extremity Manual Muscle Test (p = 0.0029), and mean change in the Ashworth score for spasticity (p = 0.021).

    Andrew Blight, Ph.D, Chief Scientific Officer of Acorda Therapeutics, commented, "Walking impairment is one of the most pervasive and serious disabilities afflicting people with MS, and there are no currently approved therapies that are indicated to improve walking in this population. Fampridine-SR, if approved, may offer a novel treatment for improving walking ability in people with MS, one that may be complementary to currently available therapies. In this study, we also saw improvements in measures of leg strength and spasticity compared to the placebo group. In particular, even the Fampridine-SR group that did not show a consistent walking improvement still showed a statistically significant improvement in leg strength compared to the placebo group. Further clinical studies would be required to determine whether such additional improvements may be clinically significant."

    Study discontinuations due to adverse events occurred in 11 (4.8%) of the 229 Fampridine-SR-treated patients, and none of the 72 patient placebo group. Three of these events were considered serious: influenza, sepsis and anxiety. The anxiety was considered probably related to treatment. A focal seizure, observed during the sepsis, was considered possibly related to treatment. An additional 13 patients in the Fampridine-SR-treated group experienced various serious adverse events but none of these led to discontinuation from treatment and none was considered related to treatment. Most non-serious adverse events were rated as mild to moderate in intensity and observed at similar rates in Fampridine-SR and placebo groups. Some events were seen more frequently in the Fampridine-SR group (insomnia, fatigue, back pain, balance disorder) while upper respiratory infection was more common in the placebo group. Overall, the safety data were consistent with previous experience.

    Study Design

    The double-blind, placebo-controlled trial was designed to evaluate the safety and efficacy of Fampridine-SR in improving walking ability in people with MS. The trial, which enrolled 301 individuals at 33 MS centers in the United States and Canada, recruited patients between 18 and 70 years old with a definite diagnosis of MS and some degree of walking disability. The study was open to people with all types of MS, including primary-progressive, secondary-progressive, relapsing-remitting and progressive-relapsing. Participants were permitted to remain on a stable regimen of their current medications, including immunomodulators. Secondary endpoints for the trial included the Lower Extremity Manual Muscle Test, the Ashworth Score for spasticity, and Subject and Clinician Global Impressions. Subjects were randomised to 14 weeks of treatment with Fampridine-SR (n=229) or placebo (n=72), a 3:1 ratio of drug to placebo. The safety measures in this trial included a physical examination and vital signs at each study visit, ECG, laboratory tests, and tests of drug plasma concentration in addition to adverse event monitoring.

    Key inclusion criteria for the study included the ability to complete the Timed 25 Foot Walk twice at screening with times averaging between 8 and 45 seconds, having a confirmed diagnosis of MS and having a stable condition. Key exclusion criteria included a history of seizures, having previous treatment with fampridine or having an MS exacerbation within 60 days of screening.

    About Fampridine-SR

    Fampridine-SR is a sustained-release tablet formulation of the investigational drug fampridine (4-aminopyridine, or 4-AP). Data collected in laboratory studies found that fampridine can improve the communication between damaged nerves, which may result in increased neurological function.

    Fampridine-SR Mechanism of Action

    A nerve cell has one extension, called an axon, which it uses to communicate via electrical signals to other nerve cells. All but the smallest axons have a special covering of a fatty substance called myelin that acts as insulation to preserve and speed these nerve signals, much like the insulating cover of an electrical cord helps preserve the transmission of electricity.

    In MS, the myelin becomes damaged and the axon cannot effectively transmit electrical impulses. Specifically, the damaged myelin exposes channels in the membrane of the axon, which allow potassium ions to leak from the axon, dissipating the electrical current. Fampridine-SR blocks these exposed channels, and helps the electrical signals to pass through areas of damage.

    Source: Source: Acorda Therapeutics, Inc.(03/05/07)

    Acorda to conduct additional late-stage trial for its MS drug
    Acorda Therapeutics Inc. said it would conduct an additional late-stage trial for its experimental multiple sclerosis drug to establish substantial evidence of effectiveness, based on a feedback from the regulators.

    In September, the company had reported positive data from its earlier late-stage trial of the drug, Fampridine-SR. The drug is designed to improve the walking speed of patients with multiple sclerosis.

    Source: Reuters.com © Reuters 2006 (08/12/07)

    Acorda Therapeutics Announces Positive Results of Phase 3 Study of Fampridine-SR on Walking in People with Multiple Sclerosis
    Acorda Therapeutics, Inc. today announced positive results from its Phase 3 clinical trial of Fampridine-SR on walking in people with multiple sclerosis (MS). Statistical significance was achieved on all three efficacy criteria defined in the Special Protocol Assessment (SPA) by the Food and Drug Administration (FDA). A significantly greater proportion of people taking Fampridine-SR had a consistent improvement in walking speed, the study's primary outcome, compared to people taking placebo (34.8 percent vs. 8.3 percent) as measured by the Timed 25-Foot Walk (p less than 0.001). In addition, the effect was maintained in this study throughout the 14-week treatment period (p less than 0.001) and there was a statistically significant improvement in the 12-Item MS Walking Scale (MSWS-12) for walking responders vs. non-responders (p less than 0.001).

    The average increase in walking speed over the treatment period compared to baseline was 25.2 percent for the drug group vs. 4.7 percent for the placebo group. Increased response rate on the Timed 25-Foot Walk was seen across all four major types of MS. In addition, statistically significant increases in leg strength were seen in both the Fampridine-SR Timed Walk responders (p less than 0.001) and the Fampridine-SR Timed Walk non-responders (p=0.046) compared to placebo. The Company intends to present comprehensive data at an upcoming medical meeting.

    "We are delighted with the results from this trial, which are consistent with Acorda's prior Phase 2 study in people with MS. We will request a meeting with the FDA as soon as possible to discuss next steps for the Fampridine-SR program," said Ron Cohen, M.D., President and CEO. "Acorda is committed to the development of therapies that will improve the function and lives of people with MS, and we wish to thank the physicians and people with MS who participated in this trial."

    "Many people with MS experience nerve damage that eventually impairs walking. Currently, no therapies are indicated to improve neurological function, such as loss of mobility, in MS," said Andrew Goodman, M.D., Director of the Multiple Sclerosis Center at the University of Rochester. "Based on the results of this trial, Fampridine-SR could represent a new way to treat people with MS. In this study, a significantly higher proportion of subjects experienced a consistent improvement in walking speed with Fampridine-SR than with placebo, and this was accompanied by a reduction in the degree of disability that the subjects reported in their daily activities related to mobility."

    Special Protocol Assessment (SPA)

    This clinical trial was conducted under an SPA from the FDA. The efficacy criteria set forth in the SPA included three elements:

    • To show that there were significantly more responders in the Fampridine-SR treated group than in the placebo group, as measured by the Timed 25-Foot Walk, a standard neurological test. A responder was defined as someone whose walking speed on the Timed 25-Foot Walk was consistently greater during at least three of four on-drug visits than the person's fastest speed on any of the five off-drug visits.
    • To demonstrate statistically significant improvement in walking speed on the last on-drug visit for the Fampridine-SR-treated responders compared to the placebo group.
    • To show that responders reported a significantly greater improvement than non-responders on the MSWS-12, a self-rated assessment of walking disability. This step was meant to validate the clinical meaningfulness of consistent improvement on the Timed 25-Foot Walk.

    Study Design

    The double-blind, placebo-controlled trial was designed to evaluate the safety and efficacy of Fampridine-SR in improving walking ability in people with MS. The trial, which enrolled 301 individuals at 33 MS centers in the United States and Canada, recruited patients between 18 and 70 years old with a definite diagnosis of MS and some degree of walking disability. The study was open to people with all four major types of MS, including primary-progressive, secondary-progressive, relapsing-remitting and progressive-relapsing. Participants were permitted to remain on a stable regimen of their current medications, including interferons. Secondary endpoints for the trial included measurements of leg strength. Subjects were randomised to 14 weeks of treatment with Fampridine-SR (n=229) or placebo (n=72), a 3:1 ratio of drug to placebo.

    Safety Statement

    In this study, adverse events were largely consistent with the safety profile observed in previous studies of Fampridine-SR in people with MS, including an increased risk of seizures that appears to be dose related. Following is a list of the most common adverse events reported in the study, with percentages representing the Fampridine-SR treatment group vs. the placebo group: falls (15.8 percent vs.15.3 percent), urinary tract infection (13.6 percent vs.13.9 percent), dizziness (8.3 percent vs. 5.6 percent), insomnia (8.3 percent vs. 4.2 percent), fatigue (6.1 percent vs. 2.8 percent), nausea (6.1 percent vs. 4.2 percent), upper respiratory tract infection (6.1 percent vs. 9.7 percent), asthenia (5.7 percent vs. 6.9 percent), back pain (5.7 percent vs. 0 percent), balance disorder (5.7 percent vs. 2.8 percent) and headache (5.7 percent vs. 5.6 percent).

    Two serious adverse events that were judged potentially related to treatment and led to discontinuation were anxiety in one subject and a seizure in another subject that was observed during an occurrence of sepsis associated with a urinary tract infection. No deaths occurred during the study. One death was reported for a subject five weeks after the last on-drug study visit. This death occurred outside of the protocol time window for reporting adverse reactions and the cause of death is not known at this time.

    About Fampridine-SR

    Fampridine-SR is a sustained-release tablet formulation of the investigational drug fampridine (4-aminopyridine, or 4-AP). Data collected in laboratory studies found that fampridine can improve the communication between damaged nerves, which may result in increased neurological function.

    Fampridine-SR Mechanism of Action

    A nerve cell has one extension, called an axon, which it uses to communicate via electrical signals to other nerve cells. All but the smallest axons have a special covering of a fatty substance called myelin that acts as insulation to preserve and speed these nerve signals, much like the insulating cover of an electrical cord helps preserve the transmission of electricity.

    In MS, the myelin becomes damaged and the axon cannot effectively transmit electrical impulses. Specifically, the damaged myelin exposes channels in the membrane of the axon, which allow potassium ions to leak from the axon, dissipating the electrical current. Fampridine-SR blocks these exposed channels, and helps the electrical signals to pass through areas of damage.

    Source: Acorda Therapeutics, Inc. 25/09/06

    Acorda Therapeutics(R) Announces Completion of Enrollment in Fampridine-SR Clinical Trial in Multiple Sclerosis

    Acorda Therapeutics, Inc. announced today it has completed enrollment of its Phase 3 clinical trial of Fampridine-SR in multiple sclerosis. The study, which is based on a Special Protocol Assessment (SPA) issued by the Food and Drug Administration (FDA), is evaluating the safety and efficacy of Fampridine-SR in improving walking ability in people with MS.

    The primary outcome measure for the study is an improvement in walking ability; secondary outcomes include measurements of leg strength and muscle spasticity. Data from this trial are expected in the third quarter of 2006.

    Source: Acorda Therapeutics, Inc.(03/03/06)

    Acorda Therapeutics(R) Initiates Phase 3 Clinical Trial of Fampridine-SR in Multiple Sclerosis

    Acorda Therapeutics announced today that it has initiated a pivotal, Phase 3 clinical trial of Fampridine-SR in multiple sclerosis (MS).

    The study, which is based on a Special Protocol Assessment (SPA) issued by the Food and Drug Administration (FDA), will evaluate the safety and efficacy of Fampridine-SR in improving walking ability in people with MS.

    Goliath (30/06/05)

    A multi-center clinical is about to be launched in the United States and Canada to test an oral medication for multiple sclerosis(MS) designed to improve walking ability in people with the disease.

    This will be a pivotal Phase 3 clinical trial, meaning if the results turn out to be positive, an application for approval of the drug to treat MS will likely be submitted to the Food and Drug Administration. The trial's findings will serve as a basis for the application.

    Helping Nerve Fibers Communicate
    The medication, labeled Fampridine-SR, is the sustained-release, oral form of the investigational drug, Fampridine. According to its manufacturer, Acorda Therapeutics, the drug is currently being tested in several clinical trials as a therapy for both MS and spinal cord injury. In preclinical trials, the drug has been shown to improve impulse conduction in nerve fibers after myelin has been damaged....................

    For full article click the link above (05/08/05)

    © Multiple Sclerosis Resource Centre

    Related Items
    ATX-MS-1467
    Aubagio® (Teriflunomide)
    Avonex®
    AZ01
    Betaseron® (Betaferon®)
    BG-12
    Cannabis And Cannabinoid Research
    Copaxone®
    Cyclophosphamide
    Cyrevia
    Dextromethorphan
    Gilenya® (fingolimod)
    Laquinimod
    Lemtrada (alemtuzumab)
    Lisinopril
    Low Dose Naltrexone - Latest News
    Masitinib
    MIS416
    MN-166 (Ibudilast)
    NeuroVax
    Novantrone (Mitoxantrone)
    NT-KO-003
    Ocrelizumab
    ONO-4641
    PEGylated interferon beta
    PI-2301
    Rebif®
    RPC1063
    RPI-78M
    RTL-1000
    Sativex®
    SHK
    Statins
    Tcelna(TM)
    Trimesta (Oral Estriol)
    Tysabri®
    Zenapax (daclizumab)


    Did you find this information useful? Would you like to comment on this page? Let us know what you think! We welcome all comments and feedback on any aspect of our website - please click here to contact us.