Data Published in The Lancet Show Fampridine-SR Improved Walking Ability in People with Multiple Sclerosis
Currently No Medications Indicated to Improve Walking Ability in MS--
HAWTHORNE, N.Y.--(BUSINESS WIRE)--Feb. 26, 2009-- Acorda Therapeutics, Inc. (Nasdaq: ACOR) today announced the publication of Phase 3 clinical trial data on Fampridine-SR in multiple sclerosis (MS) in the February 28 issue of The Lancet, one of the world's leading medical journals. The trial, which included 301 participants at 33 leading MS centers in the U.S. and Canada, demonstrated that a significantly greater proportion of people with MS taking Fampridine-SR had a consistent improvement in walking speed compared to those receiving placebo (35 percent vs. 8 percent; p < 0.0001). Additional study assessments validated the clinical meaningfulness of improvements in walking speed, which was measured by the Timed 25-Foot Walk.
"The data in this Phase 3 clinical trial showed that a statistically significant proportion of the participants who received Fampridine-SR experienced a consistent improvement in their walking speed," said the paper's lead author and consultant to Acorda Therapeutics, Andrew Goodman, M.D., Director of the Multiple Sclerosis Center at the University of Rochester Medical Center. "Importantly, the trial also demonstrated that consistent improvement in walking speed is associated with a patient-reported improvement in the ability to carry out activities of daily living related to walking, such as walking outside of the home, standing, reduced need for assistive devices, and the ability to climb up and down stairs."
Between 400,000-500,000 people in the United States, approximately 630,000 people in Europe and up to 2.5 million people worldwide have MS. Recent studies conducted in the U.S. indicate that between 64-85 percent of people with MS have walking disability1,2. Fully 70 percent of people with MS who have walking disability report it to be the most challenging aspect of their disease1.
"The majority of people with MS experience at least some degree of walking impairment as their disease progresses, and people with MS cite walking disability as one of the most difficult and concerning aspects of their disease because it limits their independence. Currently there are no therapies indicated to improve walking ability in people with MS," said Ron Cohen, M.D., President and CEO of Acorda Therapeutics. "This trial included both physician and patient assessment scales that demonstrated both improvement in walking speed and clinical meaningfulness of that improvement. The results of this study indicate that Fampridine-SR could potentially represent an important new treatment option in managing MS."
Primary data from this clinical trial were first presented at the 2007 American Academy of Neurology (AAN) annual meeting. Acorda submitted a New Drug Application (NDA) for Fampridine-SR to the U.S. Food and Drug Administration (FDA) for improvement in walking ability on January 30, 2009.
Data Demonstrate Improvement in Walking Speed and Leg Strength
A significantly greater proportion of people taking Fampridine-SR (35 percent vs. 8 percent) were classified as "Timed Walk Responders," defined as subjects with an increase in walking speed in at least three of the four on-drug clinical visits compared to the best walking speed during five off-drug visits, as measured by the Timed 25-Foot Walk. The average increase in walking speed over the 14-week treatment period compared to baseline was 25.2 percent for the drug group vs. 4.7 percent for the placebo group. This increase was maintained across the entire treatment period, and the increased response rate was seen across all four major types of MS.
In addition, statistically significant increases in leg strength as measured by the Lower Extremity Manual Muscle Test (LEMMT) were seen in both the Fampridine-SR Timed Walk responders (p=0.0002) and the Fampridine-SR Timed Walk non-responders (p=0.046) compared to placebo.
Validating the Clinical Meaningfulness of Walking Improvement
The study included several validation measures in order to assess the clinical meaningfulness of improved walking speed. The 12-Item MS Walking Scale (MSWS-12), a rating scale that captures patients' perspectives on their ambulatory disability, was used as the primary measure to validate the clinical meaningfulness of the Timed-Walk response. There was a significantly greater average improvement from baseline among Timed Walk Responders compared to non-responders (p=0.0002).
A Subject Global Impression (SGI) and a Clinician Global Impression (CGI) were used as secondary validation measures. Significant improvements were also seen on these measures among Timed Walk Responders compared to Timed Walk non-responders. The SGI asked the patients to rate their impression of the effects of the study medication during the preceding week on their physical well being using a 7-point scale (1 = terrible to 7 = delighted). The CGI measured the supervising clinician's impression of the patient's neurological condition on a 7-point scale (1 = very much improved to 7 = very much worse) at the end of the study drug period relative to the screening visit.
In addition to these measures, the authors of the paper noted that other published studies have shown timed walk speed changes of 20 percent or more qualify as meaningful change, and timed walk speed correlates with walking over longer distances and times.
Safety Profile
In this study, adverse events were largely consistent with the safety profile observed in previous studies of Fampridine-SR in people with MS. Following is a list of adverse events reported in the study that occurred in greater than 5 percent of patients taking Fampridine-SR (percentages represent the Fampridine-SR treatment group vs. the placebo group): falls (16 percent vs.15 percent), urinary tract infection (14 percent vs.14 percent), dizziness (8 percent vs. 6 percent), insomnia (8 percent vs. 4 percent), fatigue (6 percent vs. 3 percent), nausea (6 percent vs. 4 percent), upper respiratory tract infection (6 percent vs. 10 percent), asthenia (6 percent vs. 6 percent), back pain (6 percent vs. 0 percent), balance disorder (6 percent vs. 3 percent) and headache (6 percent vs. 6 percent).
Two serious adverse events that were judged potentially related to treatment with Fampridine-SR and led to discontinuation were anxiety in one subject and a focal seizure in another subject that was observed during an occurrence of sepsis associated with pneumonia.
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, 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, such as interferons. Subjects were randomized to 14 weeks of treatment with Fampridine-SR (n=229) or placebo (n=72), a 3:1 ratio of drug to placebo.
Fampridine-SR Development Program
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.
About Multiple Sclerosis
Multiple sclerosis is a chronic, usually progressive disease in which the immune system attacks and degrades the function of nerve fibers in the brain and spinal cord. Symptoms may be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision. The progress, severity, and specific symptoms of MS vary from one person to another.
For most people with MS, the disease slowly progresses with a series of unpredictable flare-ups, also called relapses. But for some, the progression of the disease is rapid. Each relapse tends to lead to increasing disabilities such as walking impairment, muscle weakness or speech or vision impairments. Within 15 years of an MS diagnosis, 50 percent of patients often require assistance walking and, in later stages, up to a third of patients are unable to walk.
Between 400,000-500,000 Americans have MS, and someone is newly diagnosed with MS every hour in the U.S. Most are between the ages of 20 and 50, and women are affected two to three times as much as men. Worldwide, MS may affect 2.5 million individuals.
About Acorda Therapeutics
Acorda Therapeutics is a biotechnology company developing therapies for spinal cord injury, multiple sclerosis and related nervous system disorders. The Company's marketed products include Zanaflex Capsules® (tizanidine hydrochloride), a short-acting drug for the management of spasticity. Acorda filed a New Drug Application (NDA) for its lead clinical product, Fampridine-SR, on January 30, 2009. Clinical trials of Fampridine-SR evaluated its safety and efficacy in improving walking ability in people with MS. The Company's pipeline includes a number of products in development for the treatment, regeneration and repair of the spinal cord and brain.
Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, regarding management's expectations, beliefs, goals, plans or prospects should be considered forward-looking. These statements are subject to risks and uncertainties that could cause actual results to differ materially, including delays in obtaining or failure to obtain FDA approval of Fampridine-SR, the risk of unfavorable results from future studies of Fampridine-SR, Acorda Therapeutics' ability to successfully market and sell Fampridine-SR, if approved, and Zanaflex Capsules, competition, failure to protect its intellectual property or to defend against the intellectual property claims of others, the ability to obtain additional financing to support Acorda Therapeutics' operations, and unfavorable results from its preclinical programs. These and other risks are described in greater detail in Acorda Therapeutics' filings with the Securities and Exchange Commission. Acorda Therapeutics may not actually achieve the goals or plans described in its forward-looking statements, and investors should not place undue reliance on these statements. Acorda Therapeutics disclaims any intent or obligation to update any forward-looking statements as a result of developments occurring after the date of this press release.