Acorda Therapeutics Announces Positive Results of Phase 3 Study of
Fampridine-SR on Walking in People with Multiple Sclerosis
-Statistical significance achieved on all three efficacy criteria set
forth in SPA- HAWTHORNE, NY -- September 25, 2006 -- Acorda
Therapeutics, Inc. today announced positive results from its Phase 3
clinical trial of Fampridine-SR on walking in people with multiple
sclerosis (MS). Statistical significance was achieved on all three
efficacy criteria defined in the Special Protocol Assessment (SPA) by
the Food and Drug Administration (FDA). A significantly greater
proportion of people taking Fampridine-SR had a consistent
improvement in walking speed, the study's primary outcome, compared
to people taking placebo (34.8% vs. 8.3%) as measured by the Timed 25-
Foot Walk (P <.001). In addition, the effect was maintained in this
study throughout the 14-week treatment period (P <.001) and there was
a statistically significant improvement in the 12-Item MS Walking
Scale (MSWS-12) for walking responders vs. non-responders (P <.001).
The average increase in walking speed over the treatment period
compared to baseline was 25.2% for the drug group vs. 4.7% 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 <.001) and the Fampridine-SR
Timed Walk non-responders (P =.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, MD,
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, MD, 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 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 randomized 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% vs.15.3%), urinary tract infection (13.6% vs.13.9%),
dizziness (8.3% vs. 5.6%), insomnia (8.3% vs. 4.2%), fatigue (6.1%
vs. 2.8%), nausea (6.1% vs. 4.2%), upper respiratory tract infection
(6.1% vs. 9.7%), asthenia (5.7% vs. 6.9%), back pain (5.7% vs. 0%),
balance disorder (5.7% vs. 2.8%) and headache (5.7% vs. 5.6%). 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 MS Multiple sclerosis
is a chronic, usually progressive disease of the central nervous
system in which the immune system attacks and destroys the structure,
and therefore degrades the function, of nerve cells. Approximately
400,000 Americans have MS, and every week about 200 people are newly
diagnosed. 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 recent
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 or exacerbations. 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. Approximately 80% of people with MS experience
some form of walking disability. Within 15 years of an MS diagnosis,
50% of patients often require assistance walking and in later stages,
about a third of patients are unable to walk. 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.
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