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.

Responders 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)

Federal 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)

Biogen 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)

Acorda 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)

Acorda 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)

Acorda 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)

Acorda 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)

Data 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)

Acorda 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)

Acorda 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 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 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)

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, 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)

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)

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)

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)

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)

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)

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.

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™

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, 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)

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, 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)

"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)

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)

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)

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, 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 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)