September 20, 2008
Acorda Therapeutics Presents Additional Data From Second Positive Phase 3 Study of Fampridine-SR at World Congress on Treatment and Research in Multiple Sclerosis
Acorda Therapeutics, Inc. (NASDAQ: ACOR) today announced additional data from its second Phase 3 clinical trial of Fampridine-SR (MS-F204) on walking ability in people with multiple sclerosis (MS) at the late breaking news session of the World Congress on Treatment and Research in Multiple Sclerosis, being held in Montreal, Canada. 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% vs. 9.3%), as measured by the Timed 25-Foot Walk (p less than 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).
New findings and information presented at the meeting from the study included:
-- The response rate for Fampridine-SR treated patients was higher than placebo across all MS subtypes. Response rates for the four major MS subtypes in the study were: relapsing-remitting: 37.2%; secondary-progressive: 45.9%; primary-progressive: 50.0%; and progressive-remitting: 40.0%.
-- 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).
"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," said Andrew Goodman, M.D., Director of the Multiple Sclerosis Center at the University of Rochester, who presented the data. "The results of this study, which were consistent with the first Phase 3 Fampridine-SR trial, show that Fampridine-SR may provide benefit to people with walking difficulties."
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 primary endpoint of the study was response on the Timed 25-Foot Walk. A Fampridine-SR Timed Walk responder was defined as a study participant whose walking speed was faster during at least three of the four on-drug visits than any speed measured during the five off-drug visits. This Timed Walk Response was validated for clinical meaningfulness in previous trials by showing that the response was associated with significant improvements in day-to-day disability, as measured by the 12-item MS Walking Scale (MSWS-12), and was also associated with significant improvements in both Subject and Clinician Global Impression scores. The trial, which enrolled 240 individuals at 39 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. Subjects were randomized to treatment with Fampridine-SR (n=120), at a dose of 10mg twice a day, or placebo (n=119), and the study was open to people with all four major types of MS: primary-progressive, secondary-progressive, relapsing-remitting and progressive-relapsing. Participants were permitted to remain on a stable regimen of their current medications, including immunomodulators.
In this study, adverse events were generally mild to moderate and largely consistent with the safety profile observed in previous studies of Fampridine-SR in people with MS. The most common adverse events reported in the Fampridine-SR treatment group compared to the placebo group included: urinary tract infection (17.5% vs. 8.4%), falls (11.7% vs. 16.8%), insomnia (10.0% vs. 1.7%), headache (9.2% vs. 0.8%), asthenia (8.3% vs. 4.2%), dizziness (8.3% vs. 0.8%), nausea (8.3% vs. 0.8%), back pain (5.8% vs. 2.5%), balance disorder (5.8% vs. 1.7%), upper respiratory tract infection (5.8% vs. 6.7%), arthralgia (5.0% vs. 4.2%), nasopharyngitis (5.0% vs. 4.2%) and paraesthesia (5.0% vs. 1.7%).
There were three serious adverse events (SAEs) that led to discontinuation: two in the placebo group and one in the Fampridine-SR group. In the placebo group, one participant experienced a possible complex partial seizure and another experienced a combination of chest tightness and gastric reflux. Both of these events were judged by investigators, who were blinded at the time, to be possibly related to treatment. In the Fampridine-SR group, one participant had a patellar fracture, which was judged not to be treatment related. In addition, one participant treated with Fampridine-SR experienced an episode of syncope (fainting) one day after completing the treatment phase of the study. This was judged to be possibly related to treatment, but the participant was not discontinued from the trial. Follow-up assessment by the clinical investigators determined that these SAEs resolved completely with no residual effects. No deaths occurred during the study.
As of August 5, 2008, the total exposure in our MS studies to Fampridine-SR at 10mg twice a day, including both double-blind and open-label studies, is approximately 1,200 patient years. The incidence of seizures in these studies at the 10mg dose has been within the rates reported for placebo-treated groups in long-term controlled studies of immunomodulator drugs in MS patients. These rates have ranged up to two percent of patients in a two-year study, or one seizure per 100 patient years. The overall incidence of seizure appears to be dose-related.
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. Over 400,000 Americans have MS, and someone is newly diagnosed with MS every hour in the United States. 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.
According to the National Multiple Sclerosis Society (NMSS), the direct costs of medical care for MS patients in the United States exceed $6 billion annually. Additionally, a NMSS analysis estimated the total cost of MS, including medical and non-medical care, production losses, and informal care, at more than $47,000 per U.S. patient per year. Complications from MS may make it harder for people to work and may interfere with their ability to perform common daily activities.
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. Research indicates 64% -85% of people with MS have difficulty walking, and 70% of people with MS who have difficulty walking report it to be the most challenging aspect of their MS. 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.
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 completed a second Phase 3 clinical trial to evaluate its safety and efficacy in improving walking ability in people with MS in June 2008.
Fampridine-SR and MS
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. In published studies, fampridine has been shown to block these exposed channels and help the electrical signals to pass through areas of damage.
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(R) (tizanidine hydrochloride), a short-acting drug for the management of spasticity. Acorda's lead clinical product, Fampridine-SR, recently completed a second Phase 3 clinical trial to evaluate 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.
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.