Possible Drugs For The Treatment Of MS Symptoms

Drugs Progressing To Full Clinical Trials

• Zenvia
• Tolperisone (AV650)
• MCT-125

Concert Pharmaceuticals has joined forces with New York-based Fast Forward, a subsidiary of the National Multiple Sclerosis Society, to fund the pre-clinical advancement of a new drug developed by the company, C-21191, to treat spasticity and pain in people suffering from MS.

“This collaboration with Fast Forward enables us to accelerate development of C-21191 and will provide our team with valuable insight into the management of symptoms associated with multiple sclerosis,” said Roger Tung, president and CEO of Concert Pharmaceuticals. “It further validates our novel deuterated chemical entity platform as a highly efficient approach to creating innovative compounds like C-21191 by leveraging previous industry R&D (research and development) investment.”

Based in Lexington, Concert Pharmaceuticals is a clinical stage biotechnology company focused on applying the company’s deuterated chemical entity platform to create small molecule drugs.

Fast Forward focuses on speeding up multiple sclerosis treatments by connecting university-based MS research with private-sector drug development and by funding small biotechnology and pharmaceutical companies to develop innovative MS therapies and repurpose FDA-approved drugs as new treatments for MS.

Spasticity refers to a debilitating symptom associated with multiple neurological disorders, including cerebral palsy, multiple sclerosis, spinal cord injury and stroke.

Source: Boston Herald © Copyright by the Boston Herald and Herald Media (06/03/12)

According to the authors of a study from Research Triangle Park, North Carolina, "We assessed the efficacy and tolerability of gabapentin enacarbil in the treatment of moderate to severe primary restless legs syndrome and associated sleep disturbance. This was a multicenter, randomized, double-blind, placebo-controlled, 2-period crossover polysomnography study of gabapentin enacarbil 1200 mg or placebo taken once daily."

"Subjects were randomized 1:1 to a sequence of gabapentin enacarbil: placebo or placebo: gabapentin enacarbil, receiving each treatment for 4 weeks. The primary end point was the mean change from baseline at weeks 4 and 10 (4/10) last observation carried forward in wake time during sleep.

The key secondary end point was the mean change from baseline at weeks 4/10 last observation carried forward in periodic limb movements associated with arousal per hour of sleep. Tolerability assessments included adverse events.

One hundred thirty-six subjects were randomized (gabapentin enacarbil: placebo, 67; placebo: gabapentin enacarbil, 69), and 114 (gabapentin enacarbil: placebo, 53; placebo: gabapentin enacarbil, 61) completed the study.

Gabapentin enacarbil 1200 mg significantly reduced wake time during sleep (mean change from baseline [adjusted mean treatment difference]: -26.0 minutes; P< .0001) and periodic limb movements associated with arousal per hour of sleep (adjusted mean treatment difference: -3.1 periodic limb movements with arousal/hour; P = .002) compared with placebo at weeks 4/10 last observation carried forward.

The most commonly reported adverse events were dizziness (gabapentin enacarbil 20%, placebo 2%) and somnolence (gabapentin enacarbil 13%, placebo 2%)," wrote J.W. Winkelman and colleagues, GlaxoSmithKline.

The researchers concluded: "Gabapentin enacarbil 1200 mg once daily significantly reduces restless legs syndrome-associated sleep disturbance and periodic limb movements associated with arousal per hour of sleep and is generally well tolerated in adults with moderate to severe primary restless legs syndrome."

Winkelman and colleagues published the results of their research in Movement Disorders (Randomized Polysomnography Study of Gabapentin Enacarbil in Subjects with Restless Legs Syndrome. Movement Disorders, 2011;26(11):2065-2072).

Source: Therapeutics Daily ©2011 UBM Canon (10/11/11)

Canbex Therapeutics Ltd. (Canbex) announced today that it has received a Translation Award of up to 1.75 million ($2.8 million) from the Wellcome Trust to support development of a drug for the treatment of the debilitating muscle spasms associated with multiple sclerosis and potentially other disorders.

The award will facilitate further preclinical development of Canbex's VSN series of compounds and the progression into clinical trials. It is anticipated that a Phase I trial of lead compound VSN16R could begin in December 2012.

"We are delighted that Canbex can move their lead compound VSN16R forward towards clinical trials," said Dr Stephane Mery of Canbex.
Preclinical studies have shown that VSN16R treatment reduces muscle spasms in an animal model of MS spasticity, with a far lower burden of side effects than the decades-old compounds that are currently in clinical use. Even at high doses, animals treated with of VSN16R did not show the limpness and muscle flaccidity, know as the "rag doll effect", that is a characteristic of existing compounds.

"Multiple sclerosis (MS) patients urgently need more tolerable treatments for the painful and debilitating muscle spasms that many of them suffer, and we believe that VSN16R has the potential to meet that need, and enhance the quality of life for people living with MS" Mery added.

MS is a serious and progressive chronic disease for which no satisfactory cure is in sight. Spasticity, characterized by sudden and uncontrollable movements of limb and torso musculature, is among the most painful, damaging and debilitating symptoms of the disease. It can manifest itself in the form of gait disorders, fatigue, spasms and pain. Spasticity can also occur in other conditions, including bladder dysfunction and spinal cord injury.

Current forms of treatment for spasticity are unsatisfactory, and a drug against spasticity that is well tolerated and effective could make a substantial difference to quality of life for MS patients and potentially many others.

Canbex has been developing its VSN series of compounds with the support of investors including Fast Forward LLC, a not for profit organization established by the National Multiple Sclerosis Society, USA, to accelerate the development of treatments for MS. "Fast Forward's support has been a uniquely powerful endorsement of our efforts, one which has encouraged other funders and the MS community to engage with us," Stephane Mery said.

Source: PR Newswire Copyright © 1996-2011 PR Newswire Association LLC (24/03/11)

Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) has been approved in capsule form by the Food and Drug Administration (FDA) as the first line of treatment for uncontrolled laughing or crying, medically known as pseudobulbar affect (PBA), Avanir Pharmaceuticals Inc. announced.

People with Pseudobulbar Affect may become too emotional for no apparent reason; it is a neurologic condition in which the patient experiences involuntary, sudden and frequent episodes of crying or laughing. Patients with MS (multiple sclerosis), ALS (amyotrophic lateral sclerosis), traumatic brain injuries, stroke, as well as some other neurologic conditions can be affected with PBA. PBA episodes often occur out of proportion to the individual's underlying emotional state.

Nuedexta acts on sigma-1 and NMDA brain receptors. Exactly what mechanisms occur to reduce episodes of uncontrolled laughing or crying are not clear, experts explain. Clinical trials were carried out on participants with MS and ALS. Nuedexta safety and effectiveness for patients with Alzheimer's disease and other dementias have not been demonstrated.

Trials showed that patients on Nuedexta had considerably fewer crying or laughing episodes compared to those on a placebo.

Keith Katkin, president and CEO of Avanir said:

"The FDA approval of Nuedexta marks an important milestone for people living with PBA, an under-recognized and debilitating neurologic condition. The approval of Nuedexta also marks AVANIR's transition toward becoming a commercial enterprise, ready to support the successful launch of the first FDA-approved treatment for PBA. We expect that Nuedexta will be available by prescription during the first quarter of 2011."

Dr. Nicholas LaRocca, MS Society, Vice President of Healthcare Delivery and Policy Research, said:

"This FDA approval represents a significant step forward for people who live with the debilitating effects of PBA. For people who experience unexplained bouts of inappropriate laughing or crying, this new therapy has the potential to substantially help both them and their families."

Randall Kaye, MD, Chief Medical Officer, Avanir Pharmaceuticals, said:

"Today's approval of NUEDEXTA is a testament to the conviction of the patients and researchers who participated in our studies and represents over 10 years of research and development by our dedicated employees. We are very pleased to bring the first proven treatment option to the many patients in the U.S. living with PBA. I would like to thank FDA for working closely with us to make NUEDEXTA available."

Dr. Erik Pioro, Cleveland Clinic, Director of ALS Section, also a researcher in the Nuedexta clinical trials, said:

"PBA is a disabling neurologic condition commonly found in patients with underlying neurologic diseases or injuries. These patients frequently experience embarrassment due to their unpredictable emotional outbursts, leading to disruption of their interpersonal relationships and social isolation. As a physician who has cared for many patients with PBA, I am pleased that there is now a safe and effective treatment option for PBA that may help these patients regain more control over their daily lives and live with dignity."

Patients with PBA are often misdiagnosed with depression. PBA patients with unpredictable and involuntary displays of emotion may become anxious and extremely embarrassed, especially when there are many people around. In some cases the individual may avoid social situations. This deliberate move towards isolation may seem like a sign of depression. However, some patients do have both, PBA and depression.

According to Avenir, over 1 million Americans are moderately or severely affected with PBA.

Avenir, in its PBA web site writes:

"Although PBA occurs secondary to neurologic diseases and brain injuries, it is a distinct neurologic disorder, which can be diagnosed and treated separately from an underlying neurologic disease or injury."

Source: Medical News Today © 2010 MediLexicon International Ltd (31/10/10)

Abstract

Background: Memantine, an NMDA antagonist, is effective for moderate to severe Alzheimer's disease.

Objective: Determine whether memantine improves cognitive performance (CP) among subjects with multiple sclerosis (MS) and cognitive impairment (CI).

Methods: This double-blind, randomized, placebo-controlled trial (Clinicaltrials.gov NCT00300716) compared memantine 10 mg twice a day (4 week titration followed by 12 weeks on the highest tolerated dose) with placebo. The primary outcome was the change from baseline to exit on the Paced Auditory Serial Addition Test (PASAT) and the California Verbal Learning Test-II (CVLT-II) Long Delay Free Recall (LDFR). Secondary outcomes included additional neuropsychological tests; self-report measures of quality of life, fatigue, and depression; and family/caregiver reports of subjects' CI and neuropsychiatric symptoms.

Results: The differences between the groups on the change on the PASAT (placebo-memantine = 0.0 correct responses, 95% CI 3.4, 3.4; p = 0.9) and on CVLT-II LDFR (placebo-memantine = -0.6 words, 95% CI -2.1, 0.8; p = 0.4) as well as on the other cognitive tests were not significant. Subjects on memantine had no serious adverse events (AEs) but had more fatigue and neurological AEs as well as, per family members' reports, less cognitive improvement and greater neuropsychiatric symptoms than subjects on placebo.

Conclusion: Memantine 10 mg twice a day does not improve CP in subjects with MS, ages 18-65, without major depression, who have subjective cognitive complaints and perform worse than one SD below the mean on the PASAT or on the California Verbal Learning Test-II (total recall or delayed free recall).

Lovera J, Frohman E, Brown T, Bandari D, Nguyen L, Yadav V, Stuve O, Karman J, Bogardus K, Heimburger G, Cua L, Remingon G, Fowler J, Monahan T, Kilcup S, Courtney Y, McAleenan J, Butler K, Wild K, Whitham R, Bourdette D.

Louisiana State University Health Sciences Center, Dept Neurology, New Orleans, LA, 70003, USA.

Source: Pubmed PMID: 20483885 (28/05/10)

Results from two randomized, active-controlled clinical trials in patients with blepharospasm and cervical dystonia -- one placebo-controlled spasticity trial and one upper limb spasticity trial -- were presented at the Movement Disorder Society (MDS) 13th annual International Congress in Paris, France. The studies were sponsored by Merz Pharmaceuticals, which plans to file a Biologic License Application (BLA) for NT-201 in the USA in the near future.

"The results of these studies reaffirm our beliefs that NT-201 (Xeomin(R); botulinum neurotoxin free from complexing proteins), can be used to potentially aid focal dystonia and post-stroke spasticity sufferers," said Eric Pappert, M.D., Vice President of Medical Affairs, Merz Pharmaceuticals, USA. "In addition, NT-201 showed results in treating upper limb spasticity sufferers of various etiologies including stroke, brain injury, spinal cord injury, multiple sclerosis or cerebral palsy, warranting additional studies as a potential treatment option for a wide scope of patients."

NT-201 is a neurotoxin therapy free from complexing proteins due to a combination of high biologic activity with low bacterial protein load. It has been approved for marketing in Europe since 2007 to treat various movement disorders, and more recently approved in Canada for the indications of symptomatic management of blepharospasm, cervical dystonia and post-stroke spasticity of the upper limb. "Studies in Europe have shown non-inferiority of NT-201 to one other botulinum toxin in the treatment of cervical dystonia," said Pappert.

First Study - Title

Overall clinical efficacy and overall tolerability of NT-201 (Xeomin(R); botulinum neurotoxin free from complexing proteins) authored by R. Benecke, S. Grafe, I. Sassin, and G. Comes.

Method

Efficacy in focal dystonia was analyzed on the pooled data from 2 pivotal clinical trials in blepharospasm and cervical dystonia (343 NT 201 patients; 340 BTXCo* patients) and 1 post-stroke spasticity trial (73 NT 201 patients and 75 placebo patients). For the safety analyses, 6 clinical trials (blepharospasm, cervical dystonia, and upper limb spasticity) have been included (n=539 NT 201, n=442 BTXCo and n=75 placebo subjects). For the post-launch evaluation spontaneously reported adverse events were analyzed.

Results

In the randomized, active-controlled, double-blind studies in focal dystonia NT 201 and one other Botulinum toxin (BTXCo) have been used with a dose ratio of 1:1. The results demonstrate equivalent efficacy between the NT 201 and BTXCo. Onset, waning, and duration of effect were comparable. These findings have been confirmed by the Physician´s Global Impression of Efficacy: 70.6% of BTXCo patients and 71.8% of the NT 201 patients were rated as "good" or "very good." Additionally, in the placebo-controlled spasticity trial 62% of the caregivers rated the efficacy as good or very good compared to placebo (33%). 26.7% of patients in the NT 201 group, 26.0% in the BTXCo group, and 22.7% in the placebo group reported an adverse event. There were no clinically relevant differences between the two active treatment groups in the focal dystonia trials and between NT 201 and placebo in the post-stroke spasticity trial concerning safety aspects. All adverse reactions were either already known and/or were considered by the physician unlikely to be related to NT 201. More than 67,000 patients have been treated so far and no new safety concerns have been reported.

Second Study - Title

NT201 (Xeomin(R); botulinum neurotoxin free from complexing proteins) is efficacious and well-tolerated in upper limb spasticity of various etiologies authored by Barnes, M., Schnitzler, A., Amaral e Silva, A., Aquilar, M., Lehnert-Batar, A., and Minnasch, P.

Method

Responder analysis of at least 1-point improvement from baseline to week 4 on the Disability Assessment Scale [DAS] for the primary therapeutic target after injection of a 20 U/mL dilution or 50 U/mL dilution was evaluated. After injection, observation over a 12-week period was followed by 8 weeks safety follow-up. Botulinum neurotoxin doses were derived from the recommendations from the organization WE MOVE. The individual injection pattern was adapted to patient's needs. A two-sided 95% Newcombe-Wilson confidence interval [CI] for the difference between groups was calculated.

Results

192 patients with upper limb spasticity caused by either stroke (88%), brain injury (5.7%), multiple sclerosis (0.5%) or cerebral palsy (1.6%) were randomized to the 50 U/mL dilution group (95 patients) or to the 20 U/mL dilution group (97 patients). Limb position (60.4%), Dressing (24.0%), Hygiene (9.4%) and Pain (6.3%) were chosen as primary therapeutic target on the DAS. The maximum injected total dose was 495 units NT 201. Four weeks after injection 57.1% of patients had an at least 1-point DAS reduction from the baseline score for their primary therapeutic target. No dilution group was inferior to each other regarding efficacy. 79.9% of patients and 89.0% of investigators reported an improvement in global assessment of efficacy at week 4. There were no relevant differences regarding safety between groups.

Source: Merz Pharmaceuticals (09/06/09)

Cognition Pharmaceuticals LLC announced positive results from a Phase 2 clinical trial of C105 (l amphetamine sulfate) on 151 Multiple Sclerosis patients with documented cognitive dysfunction.

In the six-week placebo-controlled study, Cognition Pharmaceuticals reported, the active group obtained significantly higher scores on secondary outcome measures of memory and learning, including the Brief Visuospatial Memory Test - Revised, Total Recall (p = 0.041) and Delayed Recall (p < 0.01), and the California Verbal Learning Test, Long Delay Free Recall (p = .012). Safety data were unremarkable with a limited side-effect profile.

The company said that C105 demonstrated efficacy in improving memory function in patients with cognitive impairment secondary to MS. At the 30mg peak dose, the active group exhibited statistically significant improvement in performance on measures of both verbal and nonverbal delayed recall as well as improved memory retention.

Merit Designation
A report of the study findings has been awarded a Merit designation by the International Neuropsychological Society in anticipation of its 2009 conference in Atlanta where the study will be presented. The International Neuropsychological Society is a multi-disciplinary non-profit organization dedicated to enhancing communication among the scientific disciplines which contribute to the understanding of brain-behavior relationships. The Merit designation means that the abstract was identified as being among the most highly rated of all research submitted and reviewed for the meeting.

Study Results
While the results did not reach statistical significance for either of the two primary outcome measures focusing on processing speed and executive function (the Symbol Digit Modalities Test and the Subject's Global Assessment), the significant memory findings coupled with an encouraging safety profile clearly define the drug's effects and differentiate it from d-amphetamine in clinically meaningful ways, Cognition Pharmaceuticals said. Continued analyses of study data in several domains is in process.

"We are extremely encouraged by very strong findings in the areas of verbal and visual memory and learning from our trial. These memory results are consistent with and fit well with our understanding of the mechanism of action of C105 as documented in a range of preclinical and clinical studies," according to Cognition Pharmaceuticals President and Chief Scientific Officer David Erlanger, Ph.D.

The potential for C105 to help human memory was first identified by a team of researchers led by Mark Bear, Ph.D., currently Director of the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology. "In animals, we discovered that C105 can modulate memory consolidation -- a biochemical process by which temporary or labile changes in synaptic function are made enduring. We believe that C105 augments the function of modulatory systems in the brain that normally control memory strength. It is very exciting to see that this insight may be of therapeutic significance in humans with memory disorders."

Analyses of the full dataset from the trial are ongoing, with Drs. Ralph Benedict and Frederick Munschauer of the Jacobs Neurological Institute in Buffalo, New York serving as Co-Principal Investigators. A series of discussions with leading medical experts and publication of more detailed results over the coming months are under way.

About the Study
The Phase 2 trial was conducted by Cognition Pharmaceuticals, which described it as a randomized, double-blind, placebo-controlled, dose-titration study. A total of 151 subjects from 33 sites in the United States were randomized into the six-week trial at a ratio of 2:1, active to placebo. The population was composed of patients with a clinically definitive diagnosis of Multiple Sclerosis with evidence of cognitive impairment at intake. Inclusion criteria mandated that all enrolled patients demonstrate a pattern of impairment on the Symbol Digit Modalities test (a measure of processing speed), the California Verbal Learning Test (a measure of verbal learning and memory) and the Paced Auditory Serial Addition Test (a measure of working memory).

Patients were screened for depression at intake, and those with evidence of an untreated Major Depressive Disorder were excluded. Dose was titrated over 14 days, and patients remained on a therapeutic dose for another 14 days. Patients were administered a standardized cognitive assessment battery (MACFIMS; Minimal Assessment of Cognitive Function in Multiple Sclerosis) at screening and stable peak dose, and a subset of this battery was administered on intervening study days and at a follow up visit.

Next Steps
The company said it was ready to initiate a pivotal study that establishes the endpoints for Phase III MS trials. Appropriate measures have been validated for use in the U.S. and Europe. It is anticipated that C105 can be submitted for NDA in early 2011 in this most direct path to approval. Additional plans for approval in other, larger markets, including Learning Disorders and Mild Cognitive Impairment, have also been developed.

About L-amphetamine sulfate
The levo enantiomer of amphetamine sulfate (l-amphetamine) is similar to dextro enantiomer (d-amphetamine), a widely used central nervous system (CNS) stimulant (known commercially as Dexedrine). Both C105 and d-amphetamine have similar activating properties for norepinephrine; however, C105 has a significantly smaller effect on dopamine resulting in a potent CNS stimulant with fewer unwanted side effects, including lower abuse potential. In multiple Phase I and II trials completed to date, C105 has demonstrated positive efficacy data and a favorable safety profile.

Source: MarketWatch © 2008 MarketWatch, Inc (19/12/08)

IMPAX Laboratories, Inc. announced that it met with representatives of the U.S. Food and Drug Administration (FDA) to review the results of its IPX056 clinical development program and discuss next steps in development leading to submission of a new drug application (NDA). IPX056 is an investigational extended-release formulation of baclofen, the drug of choice in the treatment of spasticity, which has the potential to offer improved control of symptoms and dosing convenience.

As previously announced, IPX056 met its clinical endpoints in a Phase III study of spasticity in multiple sclerosis patients. The randomized, placebo and active comparator-controlled double blind Phase III study enrolled 173 MS patients and included a seven-week open label extension. The primary efficacy endpoint, a reduction in spasticity as measured by Ashworth score following a single dose, was statistically significant for all active treatments, including IPX056 formulations and baclofen, compared to placebo. Results from the open label extension suggest that IPX056 reduced morning stiffness and nighttime awakenings as compared to conventional baclofen in these patients. IPX056 was generally safe and well tolerated in the study.

In the meeting with the FDA, the Company was requested to collect additional longer-term controlled clinical data on the safety and efficacy of IPX056.

Michael Nestor, president of the Impax Pharmaceuticals division of Impax Laboratories, said, "While we are pleased with the results of our Phase III trial, we are disappointed that the FDA has increased its expectation for extended use data since our last meeting with the agency in August 2006. We are currently designing a trial, which the agency has agreed to review as a Special Protocol Assessment (SPA), to collect the data requested by the FDA. We expect to initiate the trial in the second half of next year."

The company is also evaluating the potential need to conduct a paediatric study under the Paediatric Research Equity Act (PREA) which was not invoked at the IPX056 End of Phase II meeting in August 2006. The issue of a paediatric study was first raised by FDA at the most recent meeting. The Company will hold further discussions with the agency on this subject.

"The Phase III results were positive and we gained valuable experience with the effectiveness of IPX056 in reducing symptoms of spasticity in patients with MS. Furthermore, we have insight into some aspects of the product where we believe IPX056 could offer improved control of spasticity symptoms in these patients" said Larry Hsu, Ph.D., president and chief executive officer of IMPAX Laboratories.

Source: Medical News Today © 2008 MediLexicon International Ltd (16/12/08)

IMPAX Laboratories, Inc. announced that IPX056, an investigational extended-release formulation of baclofen, has met its clinical endpoints in a Phase III study of spasticity in multiple sclerosis patients. The Company also is providing an update on its brand pharmaceutical product program, which resides in its IMPAX Pharmaceuticals Division.

In a 173-patient, placebo and active comparator-controlled double blind Phase III study with a seven-week open label follow on, IPX056 was shown to be effective versus placebo in reducing spasticity in multiple sclerosis patients. IPX056 is an extended-release formulation of baclofen, the drug of choice in the treatment of spasticity, which has the potential to offer improved control of symptoms and dosing convenience.

"We are very excited with the results of this study, and are planning to meet with the U.S. Food and Drug Administration (FDA) in the fourth quarter of this year to discuss the results of this study and determine the next steps in the submission of a new drug application (NDA) for IPX056," said Larry Hsu, Ph.D., president and chief executive officer of IMPAX Laboratories. "Such spasticity treatments represent a $1.6 billion market in the U.S. and IPX056 may fill an unmet medical need in these patients."

The IMPAX Pharmaceuticals division of IMPAX Laboratories currently has two products in its development pipeline, directed to neurology as a therapeutic focus, with four other central nervous system (CNS) specific products undergoing feasibility assessment. The Company filed an Investigational New Drug application for IPX066, a controlled-release formulation of Carbidopa/Levodopa in July 2008, and expects to initiate studies in Parkinson's disease patients by the end of this year and is targeting an NDA submission in mid-2011.

Michael Nestor, divisional president of IMPAX Pharmaceuticals said, "We are very pleased with the progress we have made in advancing our proprietary, brand products and expect to continue this progress with an expansion in our R&D staff this year. The CNS space is ideally suited to our core competency in drug delivery, as so many products are candidates for improved dosing and administration and the market is large and growing at almost 10% annually, faster than the total U.S. pharmaceutical market. In addition, the neurology market is readily addressable by a small and focused sales force, given the concentration of physicians writing prescriptions. We currently have 66 specialty sales representatives to market our products, and to serve as a contract force for others,"

Source: centredaily.com Copyright 2008 The Centre Daily Times (07/08/08)

XenoPort, Inc. and GlaxoSmithKline today announced positive top-line results from a placebo-controlled Phase 3 clinical trial designed to evaluate the potential of XP13512 (GSK1838262) to maintain efficacy over the course of nine months in patients with moderate-to-severe primary Restless Legs Syndrome, or RLS. Data from this randomized withdrawal trial showed that XP13512 was generally well-tolerated and that there was a statistically significant difference between the percentage of patients treated with XP13512 and placebo who met a pre-specified relapse criteria during the randomized phase of the study.

"The results of this study strengthen our belief that XP13512 has the potential to be a safe and effective treatment for primary RLS. Our first placebo-controlled Phase 3 efficacy trial of XP13512, with results announced in April 2007, demonstrated statistically significant benefits of XP13512 in treating RLS symptoms over 12 weeks. We are encouraged by the results of this new placebo-controlled Phase 3 clinical trial, which demonstrated that XP13512 was effective and generally well-tolerated when administered to primary RLS patients for nine months," said Ronald W. Barrett, Ph.D., chief executive officer of XenoPort.

"This study is an important next step in moving toward the submission of the NDA for XP13512, a potential new treatment for patients with primary RLS. XenoPort and GSK are committed to continuing research in this important area where there is still significant unmet medical need," said Atul Pande, M.D., senior vice president, GlaxoSmithKline Neurosciences Medicines Development Center.

Trial Design

This multi-center, randomized, placebo-controlled clinical trial enrolled 327 patients diagnosed with moderate-to-severe primary RLS. In the first phase of the trial, all patients were administered 1200 mg of XP13512, taken at approximately 5:00 p.m., for 24 weeks. Patients were assessed to determine treatment response at the end of this single-blind phase of the clinical trial. Responders were defined as those patients who met three criteria: a decrease in total International RLS (IRLS) rating scale score of six or more points compared to baseline score, a decrease in IRLS score to less than 15 and an assessment of "much improved" or "very much improved" on the Investigator Clinical Global Impression of Improvement (CGI-I). Responders were required to have been stable on 1200 mg of XP13512 for at least the last month of the 24-week treatment period.

After completing the single-blind phase, responders entered the 12-week, randomized, double-blind phase of the clinical trial. Patients randomized to the placebo group received 600 mg of XP13512 for two weeks and then received placebo for an additional ten weeks. Patients randomized to the XP13512 treatment group continued to receive 1200 mg of XP13512 for the entire 12-week, double-blind period.

The primary endpoint of the trial was the proportion of RLS patients who "relapsed," or had their RLS symptoms worsen, during the 12-week, double-blind treatment period. Patients were considered to have "relapsed" if either or both of the following occurred: 1) the patient withdrew from the clinical trial due to lack of efficacy; and/or 2) there were two consecutive study visits in which (a) the patient's IRLS score worsened by at least six points compared to the IRLS score at the point of randomization; (b) the patient achieved an IRLS score of at least 15; and (c) the patient received an assessment of "much worse" or "very much worse" as compared to the condition of the patient at the point of randomization using an Investigator Clinical Global Impression of Change (CGI-C).

Clinical Trial Results

Three hundred twenty seven patients were enrolled in the study, and 221 patients completed the 24-week, single-blind portion of the clinical trial, of which 194 (88%) met the responder criteria and were randomized to double-blind treatment.

Analysis of the primary endpoint indicated that treatment with XP13512 resulted in a statistically significant lower proportion of relapses compared to placebo during the double-blind treatment period (23% placebo compared to 9% XP13512; p= 0.0158).

During the single-blind phase of the trial, 13% and 4% of XP13512-treated patients withdrew from the clinical trial due to adverse events or lack of efficacy, respectively. The most commonly reported adverse events during the single-blind phase of the clinical trial were somnolence (30%) and dizziness (22%), which were generally mild or moderate in intensity and transient in nature.

During the double-blind phase, 0% and 3% of XP13512- and placebo-treated patients, respectively, withdrew from the trial due to adverse events. The incidence of somnolence and dizziness in XP13512-treated patients during the double-blind portion of the trial were 3% and 2%, respectively.

During the trial, there was one death that was determined to be unrelated to XP13512 treatment. There were five other serious adverse events, only one of which was judged as possibly related to XP13512 treatment.

"We are encouraged that XP13512 treatment was associated with a statistically significant difference from placebo in this randomized withdrawal study, particularly in light of the stringent criteria for relapse used in this clinical trial," added Dr. Barrett. "We are also pleased with the tolerability profile of XP13512 in this nine-month study. We look forward to reporting the top-line results of the final 12-week Phase 3 efficacy study of XP13512 in RLS patients later this quarter and the expected filing of the NDA for RLS treatment in the third quarter of this year by GSK."

About XP13512

XP13512 is a patented, new chemical entity that is designed to improve upon the clinical utility of gabapentin by taking advantage of high-capacity transport mechanisms in the gastrointestinal tract to improve absorption.

About RLS

According to the National Institutes of Health, up to 12 million people in the U.S. are afflicted with RLS across a range of severity from mild to severe. The syndrome is characterized by disturbing, unpleasant and sometimes painful sensations in the legs that result in a compelling urge to move. The discomfort is often temporarily relieved by movement. Because symptoms typically occur at night, RLS patients often suffer from sleep disruption. RLS symptoms can be debilitating - published data suggest that RLS can have an impact on quality of life equivalent to, or worse than, major chronic medical disorders such as diabetes and osteoarthritis.

Source: XenoPort, Inc. and GlaxoSmithKline (21/01/08)

Oxcarbazepine (OXC) is an anitepileptic medication recently approved as monotherapy for partial onset seizure and demonstrated to be useful in the treatment of several neuropathic pain. We performed an open-label pilot study of OXC (dosage 600-1200 mg/day) in 12 multiple sclerosis (MS) patients suffering painful paroxysmal symptoms.

Eight subjects were female and 4 male, with a mean age of 43.6 years, mean disease duration of 7.3 years and mean score at the EDSS of 3.2.

Ten patients had a relapsing-remitting disease course, 1 had secondary progressive and 1 had primary progressive course. 0.05). Two patients dropped out of the study due to adverse effects: 1 case of nausea and dizziness, 1 case of C. hyponatraemia.

The medication was well tolerated in the majority of the subjects. The study results provide a new possibility for treating painful symptoms in MS, but efficacy on PPS must be confirmed in a larger study.

Solaro C, Restivo D, Mancardi GL, Tanganelli P. Department of Neurology ASL 3 Genovese, Via Oliva 22, I-16123, Genova, Italy,

PMID: 17603770 [PubMed - in process](14/07/07)

SD118 is being jointly developed with NeuroDiscovery Ltd and its wholly owned subsidiary NeuroSolutions Ltd under a Collaboration Agreement concluded in June 2006. SD118 was previously under investigation in Japan for a different indication and now, following re-profiling and evaluation in experimental animal models, has demonstrated its potential as a new oral therapy for neuropathic pain.

The study is a double blind, placebo controlled, single dose, sequential group, dose escalation trial in healthy male volunteers to assess the safety, tolerability and pharmacokinetic profile of SD118 administered as an oral capsule. The study, involving some 40 subjects, will be conducted in a single centre in the UK under a CTA regulatory approval.

Mr Shinichi Tamura, President & CEO of Sosei, said: "I am delighted that SD118 has now moved forward into clinical development. This project has the potential to provide a valuable addition to currently available therapies in an area of notable unmet medical need"

Source: Thearapeuticsdaily.com ©2005 PharmaLive.com (04/06/07)

"These results are very encouraging and represent a major advance for XenoPort, its partners and, potentially, RLS patients," said Ronald W. Barrett, Ph.D., chief executive officer of XenoPort.

This XenoPort study was a 12-week, double-blind, placebo-controlled Phase 3 clinical trial that enrolled 222 patients who were diagnosed with moderate-to-severe primary RLS. Patients were treated with either 1200 mg of XP13512 or placebo, given once per day. The co-primary endpoints for the clinical trial were the change from baseline for the International RLS (IRLS) rating scale score at end of treatment and the percentage of patients showing significant improvement on the Clinical Global Impression of Improvement (CGI-I) scale at end of treatment.

Treatment with 1200 mg of XP13512 was associated with a statistically significant improvement in the co-primary endpoints compared to placebo. Improvements in the IRLS Scale were significantly greater for XP13512 than for placebo (-13.2 vs. -8.8: p=0.0002). At the end of treatment, significantly more patients treated with XP13512 were reported as "much improved" or "very much improved" on the CGI-I scale compared to those treated with placebo (76% vs. 39%: p less than 0.0001).

During treatment over the 12-week period, the most commonly reported adverse events for XP13512 versus placebo were somnolence (26.5% XP13512; 7.4% placebo) and dizziness (19.5% XP13512; 4.6% placebo). There were no reported serious adverse events in XP13512-treated patients.

Dr. Barrett stated, "XP13512 works by a different mechanism than currently approved RLS drugs, and therefore may offer an alternative treatment option for patients whose lives are disrupted by RLS symptoms. In addition to the robust efficacy results in this clinical trial, we are happy to see that XP13512 continues to be well tolerated as we expand the number of RLS patients who have been treated with XP13512. We intend to present further data from this clinical trial at a future medical conference."

About XP13512

XP13512 is a patented, new chemical entity that is designed to improve upon the clinical utility of gabapentin by taking advantage of high-capacity transport mechanisms in the gastrointestinal tract to improve absorption.

About RLS

According to the National Institutes of Health, up to 12 million people in the U.S. are afflicted with RLS. The syndrome is characterised by disturbing, unpleasant and sometimes painful sensations in the legs that result in a compelling urge to move. The discomfort is often temporarily relieved by movement. Because symptoms typically occur at night, RLS patients often suffer from sleep disruption. RLS symptoms can be debilitating - published data suggest that RLS can have an impact on quality of life equivalent to, or worse than, major chronic medical disorders such as diabetes and osteoarthritis.

Additional XP13512 Phase 3 Clinical Trials in RLS

XenoPort is conducting two additional Phase 3 clinical trials, including a second 12-week, double-blind, placebo-controlled Phase 3 clinical trial with the same co-primary and similar secondary endpoints as the trial for which results were announced today. In addition to 1200 mg of XP13512, this trial is also evaluating 600 mg of XP13512. The trial is expected to enroll approximately 300 RLS patients.

XenoPort is also conducting a Phase 3 clinical trial assessing the long-term efficacy of XP13512 using a placebo-controlled, "randomised withdrawal" design to evaluate relapse of RLS symptoms in XP13512-treated or placebo-treated patients who had previously achieved clinical improvement while taking 1200 mg of XP13512 for 24 weeks.

Source: XenoPort, Inc.(30/04/07)

SD118 is being jointly developed with NeuroDiscovery Ltd and its wholly owned subsidiary NeuroSolutions Ltd under a Collaboration Agreement concluded in June 2006. SD118 was previously under investigation in Japan for a different indication and now, following re-profiling, has demonstrated its potential as a new oral neuropathic pain therapy.

Sosei will shortly make a Clinical Trial Application in the UK to facilitate the Phase 1 trials commencement.

Mr Shinichi Tamura, President & CEO of Sosei, said: "I am delighted that we have been able to announce the completion of the pre-clinical work for SD118, further validating Sosei's expertise in successfully re-profiling compounds for new indications and its ability to provide potential compounds to replenish its pipeline."

About Sosei

Sosei Group Corporation. is a leading international biopharmaceutical company with significant expertise in product discovery and development. It has established a reduced risk business model primarily upon identifying new uses for established drugs and exploiting its unique position within Japanese, European and North American pharmaceutical markets by acquiring compounds from, and bringing compounds into, Japan.

About NeuroDiscovery

NeuroDiscovery Ltd is an ASX listed neurology research and development company which owns 100% of NeuroSolutions Ltd.

Source: TherapeuticsDaily. com ©2005 PharmaLive.com (26/02/07)

Results of the repeat-dose, 28-day dose-ranging trial demonstrated that daily administration of oral cannabinor was safe and well-tolerated with no serious adverse events or target organ or tissue toxicity. When evaluated for MTD in animals, oral cannabinor did not present dose-limiting toxicities when administered at doses expected to be higher than necessary to produce a therapeutic effect. In addition, the telemetric (wireless data recording) cardiac safety study demonstrated no treatment-related effect on blood pressure, heart rate or electrocardiogram (ECG) intervals at doses expected to be higher than necessary to produce a therapeutic effect. These data support findings on cardiovascular safety from previous safety and pharmacology studies where oral cannabinor showed no treatment-related effect on blood pressure, heart rate or ECG intervals.

"The completion of these MTD, repeat-dose and cardiovascular safety studies represents an important milestone for oral cannabinor and clears the way for the initiation of a Phase 1 clinical trial in humans," said Haim Aviv, Ph.D., Chairman and CEO. Pharmos expects to commence Phase 1 testing of cannabinor in the first quarter of 2007.

About Cannabinor

Cannabinor (formerly referred to as PRS-211,375), the lead synthetic CB2-selective agonist, is being developed by Pharmos as an analgesic. An intravenous Phase 2a nociceptive pain trial is underway to assess the safety and analgesic activity of different cannabinor doses in patients undergoing 3rd molar extraction and a second intravenous Phase 2a neuropathic pain trial with cannabinor is underway in subjects undergoing capsaicin-induced pain. Pharmos expects to complete both trials in early 2007. Oral cannabinor will facilitate clinical development of the compound for chronic pain conditions, with emphasis on neuropathic pain.

Source: PRNewswire-FirstCall (14/12/06)

Findings from a new study published today in the journal Neurology demonstrate that the oral medication pregabalin is significantly effective in relieving central neuropathic (nerve) pain and improves pain-related sleep disturbance and anxiety in patients with spinal cord injury. Conducted by researchers at the Pain Management Research Institute in Sydney, the study is the largest controlled clinical trial ever of patients with spinal cord injury who suffer from central neuropathic pain, a particularly persistent and severe pain condition.

Results from the study showed that patients using pregabalin (150-600 mg/day) experienced significant improvements in symptoms as early as the first week of treatment and those improvements were sustained throughout the study. Patients taking pregabalin experienced a significant reduction in the average intensity of their pain and significant improvements in pain-related sleep interference as well as a reduction in anxiety compared to those taking placebo.

"Historically it has been extremely difficult to manage patients with central neuropathic pain due to a lack of effective treatments and many people with spinal cord injury have excruciating pain," said Prof. Philip Siddall, lead investigator of the study and Clinical Associate Professor at the Pain Management Research Institute in Sydney. "The study demonstrates that pregabalin is an effective and well-tolerated therapy for treating a range of symptoms that can negatively impact overall quality of life. This study is an important step forward for clinicians trying to improve the lives of patients suffering from difficult-to-treat nerve pains."

Approximately two-thirds of patients with spinal cord injury often suffer from severe central neuropathic pain^(1,2), which is caused by a lesion or dysfunction in the central nervous system ⁽³⁾ . Patients often describe the symptoms of their pain as burning, tingling, stabbing, shooting, pricking, scalding and freezing ^(4,5,6). Chronic pain following spinal cord injury may limit a patient's ability to perform daily activities ⁽⁷⁾. Consequently, quality of life may be impaired ⁽⁸⁾. Central neuropathic pain can occur in patients with spinal cord injury, stroke, multiple sclerosis and neoplasia.

Pregabalin is believed to work by calming hyper-excited neurons or nerve cells which may be an underlying cause for various types of nerve pain. Based on the results of this study, pregabalin recently became the only therapy to receive European regulatory approval in central neuropathic pain.

About the Study

The study, sponsored by pregabalin (Lyrica(R) developer Pfizer Inc, was a multicentre, parallel-group, double-blind, randomised clinical trial comparing pregabalin with placebo over a 12-week treatment period in patients with spinal cord injury who had central neuropathic pain as defined by the International Association for the Study of Pain classification. The 12-week treatment period was preceded by a 1-week baseline period during which baseline data were collected. Patients were randomised to receive either flexible dose pregabalin (150-600 mg/day) (n=70) or placebo (n=67) taken twice daily. The primary endpoint of the study was mean pain score as measured by patient pain diary assessments which were completed daily. Patients also rated the extent to which pain interfered with sleep in a daily diary. Changes in anxiety were evaluated using the Hospital Anxiety and Depression Scale (HADS).

Results from the study showed that:

* Patients receiving pregabalin experienced significant improvements in symptoms as early as the first week of treatment and those improvements were sustained throughout the study.
* Patients receiving pregabalin experienced a significant reduction in the average intensity of their pain and significant improvements in pain-related sleep interference (p<0.001) as well as a reduction in anxiety (p<0.05) compared to those taking placebo (p<0.001).
* More than 40 percent of patients had greater than a 30 percent reduction in pain as compared to 16 percent of patients on placebo (p=0.001).
* At the end of the study, three times less patients had severe pain in the pregabalin group compared with the placebo group.
* Pregabalin was associated with a rapid and significant reduction in pain-related sleep interference (p<0.001) as well as a reduction in anxiety (p<0.05) compared to those patients taking placebo.
* The most common adverse events were somnolence and dizziness, which were typically mild to moderate and transient.

About the Pain Management Research Institute

The Pain Management Research Institute (PMRI) is headed by Professor Michael Cousins and brings together around 40 researchers and 40 clinical staff who are involved in pain research and management (http://www.pmri.med.usyd.edu.au/). The Institute also has a strong focus on education and has a number of staff involved in the delivery of a postgraduate degree program in Pain Management through the University of Sydney. This course is delivered on-line and accessible to students internationally. In 2004 the PMRI Educational Program received an international award as an "Exemplary Educational Program". Since 2005, the education program has been available to European and North American students through collaborations with the University of Edinburgh and the University of California, San Francisco.

The pain research program of the PMRI has a broad scope and has a number of teams investigating various aspects of pain epidemiology, neurobiology, psychology and treatment and has gained international recognition for its work in several areas including pain following spinal cord injury. In 1998, the Centre gained one of only eight National Health & Medical Research Council (NHMRC) of Australia awards as a "Centre of Clinical Excellence in Hospital Based Research". In 2005, the PMRI, in collaboration with the University of Queensland (Australia), University College London (UK) and Nagasaki University (Japan) was a recipient of an NHMRC Program Grant (2005-2009). Also in 2005 PMRI was the top level funded institution for a Program Grant from the NSW Health to investigate "Mechanisms and Treatment of Pain Associated with Spinal Cord Injury" (2005 - 2008).

The Pain Management & Research Centre (PMRC) is the clinical arm of the PMRI and conducts clinical treatment programs in acute pain, cancer pain and chronic non cancer pain. PMRC comprises a group of approx 40 multidisciplinary health care practitioners who evaluate all aspects of each patient's pain and recommend treatment options based upon a multidisciplinary approach. PMRC currently provides approx 40,000 episodes of patient care per annum. Each year at least four internationally funded Fellows spend a year of training with PMRC. To date Fellows have been drawn from more than 20 countries.

¹ Bonica JJ. Introduction: Semantic, epidemiologic and educational issues. In: Casey KL, ed. Pain and Central Nervous System Disease. New York: Raven Press, 1991:13-30.

² Siddall PJ, Taylor DA, McClelland JM, Rutkowski SB, Cousins MJ. Pain report and the relationship of pain to physician factors in the first 6 months following spinal cord injury. Pain 1999;81(1-2):187-197.

³ Merskey H, Bogduk N, eds. Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms. Seattle: IASP Press, 1994:209-212.

⁴ Cruz-Almeida Y, Martinez-Arizala A, Widerstrom-Noga EG. Chronicity of pain associated with spinal cord injury: a longitudinal analysis. J Rehabil Res Develop. 2005; 42(5):585-594.

⁵ Finnerup N, Johannesen I, Fuglsang-Frederiksen A, Bach FW, Jensen T. Sensory function in spinal cord injury patients with and without pain. Brain. 2003; 126:57-70.

⁶ Siddall P, McClelland JM, Rutkowski S, Cousins M. A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury. Pain. 2003; 103:249-257.

⁷ Ravensscroft A, Ahmed YS, Burnside IG. Chronic pain after SCI: a patient survey. Spinal Cord. 2000; 38:611-614.

⁸ Stensman R. Adjustment to traumatic spinal cord injury: a longitudinal study of self-reported quality of life. Paraplegia. 1994; 32:416-422.

SOURCE: Pain Management Research Institute (28/11/06)

"A cell compound such as methylthioadenosine is able to modulate the immune response, and it might become a useful therapy for autoimmune diseases with less toxicity than other drugs because the cell has several mechanisms to compensate its excess," Dr. Pablo Villoslada told Reuters Health.

Dr. Villoslada and colleagues from the University of Navarra, Spain studied the effects of intraperitoneal MTA in rodent experimental autoimmune encephalomyelitis (EAE, a model of MS) and in peripheral blood mononuclear cells from multiple sclerosis patients and healthy controls.

In the acute model, the authors report, MTA on the same day as induction of EAE prevented acute encephalomyelitis in 5 of 10 Lewis rats, whereas 9 of 10 placebo-treated animals developed neurological symptoms of acute EAE.

In rats with ongoing chronic-relapsing EAE, MTA also improved histological findings and decreased the rate of second relapse, the results indicate.

MTA treatment significantly attenuated the proliferative response of rat splenocytes to myelin basic protein and phytohemagglutinin, the researchers note, and had similar immunomodulatory effects on peripheral blood mononuclear cells from rats and from patients with MS.

"MTA would be an excellent candidate drug to be tested in patients with MS because it is safe and is effective in preventing brain autoimmune attack," the authors conclude.

"In addition," they write, "because MTA may have a pleiotropic mechanism of action in preventing T-cell activation, which is a critical step in autoimmune diseases, but without inducing immunosuppression, it appears an ideal candidate for combining with other immunomodulatory drugs to obtain a higher efficacy in stopping relapses and disease progression without increasing side effects."

Because the mechanism of action is immunomodulation by preventing T cell activation, "our target will be other autoimmune diseases and transplant rejection," Dr. Villoslada added. "We have preliminary data suggesting positive effects in type 1 diabetes and rheumatoid arthritis animal models."

Source: Ann Neurol 2006;60:323-334. (01/11/06)

Jeffrey Steenberg loves the outdoors, whether it's jogging or caring for his homemade garden. But when doctors diagnosed him with multiple sclerosis four years ago, even the simple tasks became exhausting. "Just finding myself extremely tired a lot," he says. "I couldn't make it through a day without napping."

And like about half of all MS patients, Steenberg also had memory problems. He says, "I definitely noticed some of the memory going -- calling somebody immediately after calling them and not knowing who was on the phone anymore."

Neurologist Rhonda Voskuhl, M.D., of the UCLA School of Medicine, says there's no treatment to protect patients from memory failure. "What we don't have are drugs that would be going to the brain or spinal cord and protecting those nerves," she explained.

Now, testosterone gel may do just that. In a small study, 10 men with MS applied it to their shoulders once a day for a year.

"What they reported most is that they felt better -- that they had more energy and less fatigue," Dr. Voskuhl says. The gel improved their immune systems and all the patients performed better on memory tests.

MRI scans also showed parts of the brain that normally decline in MS actually slowed.

"We're excited about these findings because we're actually would be describing the first neural protective drugs for MS," Dr. Voskuhl says.

She says researchers would most likely use an estrogen to treat women in the future. The next step is a larger clinical trial involving more men. If the gel proves to improve memory, it could also be used on patients with Alzheimer's or Parkinson's. A side effect of testosterone is it can worsen prostate cancer in patients who already have it.

Jeffrey noticed a positive difference. He says, "The increased energy and mental alertness were the biggest changes for me."

Source: News 14 Carolina Copyright ©2006 TWEAN Newschannel of Raleigh. (16/10/06)

NewsChannel5's Alicia Scicolone reported that one local doctor may have the answer, and it comes from an unusual source: snails.

Dr. Emad Mikhail, of Great Lakes Pain Management in Willoughby Hills, is the first and only doctor in Ohio to use a man-made version of snail venom to help treat patients with chronic pain.

Multiple sclerosis patient Vincina Carlo lived on the strongest narcotic pain medication out there, and on the strongest doses allowed. Still, she suffered for years.

"It was unbelievable. I couldn't walk. I couldn't do anything. There was no purpose to anything," said Carlo.

That was until she found out about a cutting-edge technique using venom from a sea predator called the cone snail.

The snail uses its venom to paralyze its prey. The idea with the new procedure is that once the pain starts, the venom stops it in its tracks.

Mikhail uses the man-made version of the venom, known as Prialt, in his treatment.

"It actually blocks the pain at the level of the spinal cord," said Mikhail.

The relief comes with help from a small catheter inserted into the spine. The catheter is hooked up to a pump in the patient's stomach.

"We program this pump to deliver this medication to the spinal cord through small doses," said Mikhail.

Those controlled doses help make Carlo pain-free.

"The minute he injected the medicine, it was an instant stopping of the pain," she said. "There was nothing like it I could describe to you in this world. It just stopped. I couldn't believe it. My life started over again."

Prialt was recently approved by the Food and Drug Administration.

Source: Newsnet5.com Copyright © 2006 NewsNet5.com (27/09/06)

Lyrica's neuropathic pain indication broadened to include central nerve pain.

Central nerve pain is associated with conditions such as spinal cord injury, stroke, and multiple sclerosis - A robust and unprecedented clinical program involving more than 10,000 patients supports Lyrica's efficacy and safety in treating a broad range of neurological disorders - Medical Expert: 'Physicians will be in a better position to manage a whole host of difficult-to-treat nerve pains for many of their patients.'

Pfizer Inc said today that the European Commission approved Lyrica(R) (pregabalin capsules) to treat central neuropathic (nerve) pain. This new approval broadens the current range of neuropathic pain that Lyrica is approved to treat in Europe to include nerve pain associated with conditions such as spinal cord injury, stroke, and multiple sclerosis. Central neuropathic pain can be an especially difficult-to-treat condition, often requiring the use of strong narcotics. Lyrica's approval in central neuropathic pain provides further evidence of its robust efficacy in even the most hard to treat neuropathic pain conditions. Now, Lyrica is the only medication approved in the EU to treat both peripheral and central neuropathic pain, which affects up to 7.7 million people in Europe.

Developed by Pfizer, Lyrica is believed to work by calming hyper-excited neurons which may be an underlying cause for various types of nerve pain.

"This approval underscores Pfizer's commitment to providing much needed therapies for complex and poorly managed pain conditions," said Dr. Joseph Feczko, Pfizer's Chief Medical Officer. "A robust and unprecedented clinical program involving more than 10,000 patients supports the efficacy and safety of Lyrica across a range of neurological disorders."

Neuropathic pain may be the result of a primary lesion or dysfunction of either the peripheral or central nervous system. Characterised by a burning, tingling and/or shock-like sensations, neuropathic pain is a type of chronic pain that is often misdiagnosed, under-treated, and a significant burden to patients, their families and society. Neuropathic pain disrupts a patients' ability to go about their daily activities. For example, patients often miss work, have difficulty concentrating and find that wearing clothing can be painful. Neuropathic pain is also associated with impairments in sleep as well as increased anxiety and depression.

Lyrica's central neuropathic pain approval was based on the largest controlled study conducted to date in central nerve pain. In a clinical trial involving 137 patients with chronic central neuropathic pain following spinal cord injury, patients taking Lyrica experienced a significant reduction in the average intensity of their pain compared to those taking placebo. Pain reduction with Lyrica was demonstrated as early as the first week of treatment and was sustained throughout the study. More than 40 percent of patients had greater than a 30 percent reduction in pain as compared to 16 percent of patients on placebo. Patients taking Lyrica also reported a significant reduction in pain-related sleep interference compared to patients taking placebo.

"This is a new day for some patients who live in excruciating pain," said Dr. Philip Siddall, Lyrica clinical trial investigator and Clinical Associate Professor at the University of Sydney Pain Management Research Institute, Sydney, Australia. "In a controlled clinical trial, Lyrica relieved excruciating nerve damage pain related to spinal cord injury for which there are currently limited treatment options. Physicians will be in a better position to manage a whole host of difficult-to-treat nerve pains for many of their patients."

Painful nerve disorders can pose a significant economic burden as patients seek relief from their pain. Since patients frequently have co-morbid conditions, such as depression and anxiety, patients are more likely to use healthcare services. Total average healthcare charges are estimated to be three-fold higher among people with painful nerve disorders, compared with the general population.

The most common adverse events reported by patients were somnolence, dizziness, edema and asthenia (fatigue). Most adverse events tended to be mild to moderate in intensity and generally dose related. Despite no known pharmacokinetic drug-drug interactions, certain adverse events which may result in impairment of cognitive and gross motor function may appear more commonly when Lyrica is co-administered with oxycodone, lorazepam or ethanol.

In 2004, Lyrica was approved for use in adults for the treatment of various peripheral neuropathic pain indications, including diabetic and post herpetic neuropathic pain, and adjunctive therapy for partial epilepsy in more than 60 countries outside of the United States. In 2006, Lyrica was also approved for the treatment of generalized anxiety disorder in Europe.

In the United States, Lyrica(R) (pregabalin) capsules C-V are approved for the management of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia, as well as for the adjunctive treatment of partial onset seizures in adults.

Source: FinanzNachrichten.de © 2000-2006 FinanzNachrichten.de (18/09/06)

"NovaDel's oral spray technology may be particularly applicable to drugs for the treatment of CNS disorders where the oral sprays ability to overcome difficulty in swallowing tablets and achieving rapid onset of action could fulfill important unmet medical needs for patients," commented Jan Egberts, M.D., CEO of NovaDel. "For instance, we expect that the ease of administering Tizanidine Oral Spray will be well suited to patients suffering from spasticity, which often includes difficulty in swallowing and drugs administered via tablet represent an obstacle to treatment.

"NovaDel's newest development candidates share several benefits common to all of the drug candidates in our pipeline," continued Egberts. "These drug candidates have ease of administration associated with oral spray that may provide substantial benefits compared with the current modes of administration and they may have improved pharmacokinetics enabling more rapid relief. Importantly, NovaDel expects both tizanidine and ropinirole oral sprays to enter clinical trials in the first quarter of 2007 and progress through the shortened 505(b)(2) regulatory process."

About Tizanidine Oral Spray

Spasticity is a symptom of several neurological disorders, including multiple sclerosis, spinal cord injury, stroke and cerebral palsy, and leads to involuntary tensing, stiffening and contracting of muscles. Tizanidine treats spasticity by blocking nerve impulses through pre-synaptic inhibition of motor neurons. This method of action results in decreased spasticity without a corresponding reduction in muscle strength. Because patients experiencing spasticity may have difficulty swallowing the tablet formulation of the drug, NovaDel's Tizanidine Oral Spray may provide patients suffering from spasticity with a very convenient solution to this serious treatment problem.

About Spasticity

Spasticity affects over 500,000 people in the U.S. alone. Spasticity is not a disease, but rather a symptom of various neurological disorders, including, but not limited to, multiple sclerosis (MS), spinal cord injury (SCI), stroke and cerebral palsy. These disorders cause a change in the balance of signals between the central nervous system and the muscles. This imbalance leads to involuntary tensing, stiffening and contracting of muscles. Tizanidine is the most widely prescribed treatment for spasticity with approximately four million prescriptions written annually.

Source: NovaDel Pharma Inc.(13th September 2006)

Aricept, a drug used in treating Alzheimer's disease, might improve memory and mental function in some people with multiple sclerosis (MS), according to a new study.

The report, published in the Nov. 9 2004 issue of the journal Neurology, focused on 69 patients with multiple sclerosis who suffered from mild declines in mental function.

Roughly half of all multiple sclerosis patients experience problems with memory and thinking, making problems with mental skills a leading cause of disability from the disease, which currently has no cure.

At the start of the new study researchers from the neurology department of the State University of New York at Stony Brook asked participants with multiple sclerosis-associated memory and mental impairment to perform memory and mental skills tests. Next, they divided the participants into two groups.

One group took Aricept for 24 weeks, starting with 5 milligrams per day and increasing to 10 daily milligrams in the study's fourth week. The other group took a placebo for 24 weeks. At 24 weeks, participants were retested.

Aricept patients had greater improvements in memory testing than the placebo group. Memory test scores for the Aricept group improved almost 14% from their initial scores. The placebo group improved less than 3% on their memory test scores. In addition, 66% of the Aricept group reportedly said their memory had gotten better, compared with only 32% of the placebo group.

No serious side effects were seen from Aricept, except for unusual or abnormal dreams, which were reported by 34% of the Aricept group and 9% of the placebo group.

Source WebMD Health (09/11/04) 

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