Slower Rates of Progression Noted for Men
April 29, 2004
Source: Teva Pharmaceutical Industries Ltd
Business Wire 2004
Treatment with COPAXONE(R) (glatiramer acetate injection) may provide
beneficial effects in patients with primary progressive multiple sclerosis
(PPMS), according to new data presented late yesterday at the 56th Annual
Meeting of the American Academy of Neurology. In a post-hoc analysis of
all available data from the intention-to-treat cohort, men treated with
COPAXONE(R) were found to have significantly slower rates of progression
of the disease than those treated with placebo. No overall benefit was
shown, a result that may have been driven by the low rate of progression
in the study population.
The primary progressive form of multiple sclerosis is the most degenerative form of MS, characterized by a slow (nearly continuous) worsening of symptoms from the onset of the disease. It is a relatively rare form of the disease, occurring in about 10 percent of multiple sclerosis patients and more typically occurs in men. Unlike the more common relapsing-remitting form of the disease, it is not associated with distinct relapses or periods of remission. No currently available treatments have shown significant positive effects in treating PPMS.
"Although the primary endpoint in our trial did not reach statistical significance, there was a trend with COPAXONE(R) to slow clinical progression," said Dr. Jerry S. Wolinsky, Bartels Family Professor of Neurology, The University of Texas Health Science Center at Houston. "We observed slower rates of progression in men on the drug. Based on these findings, additional research with COPAXONE(R) in PPMS is warranted."
The data are from an intent-to-treat analysis of the ProMiSe trial in which 943 patients (455 men) were randomized for treatment with COPAXONE(R) (glatiramer acetate injection) or placebo in a two-to-one ratio. A preplanned interim analysis of 935 patients, of whom 757 had completed at least two years or had terminated the study early, projected that no significant treatment effect could be reached for the primary endpoint, which was time to progression of Expanded Disability Status Scale (EDSS) scores (defined as change of 1.0 EDSS point or greater for entry EDSS of 3.0 - 5.0, or 0.5 for entry EDSS of 5.5 - 6.5). As a result, the study was terminated prematurely and study medications were discontinued.
Despite the termination of this study, due to the unique nature of this PPMS cohort, patients were offered the opportunity to continue to be followed. An intention-to-treat analysis at three years demonstrated trends toward delaying disease progression and decreasing the proportion of male patients demonstrating progression in favor of COPAXONE(R). The Kaplan Meier survival curve indicated delayed disease progression for males assigned to COPAXONE(R) diverged from a placebo-assigned patient curve within a year of study entry, and the gap widened over time. Additionally, an analysis of an on-study drug cohort supported a treatment effect based on MRI-monitored enhancements and plaque burden. Overall, data suggested COPAXONE(R) had a beneficial impact on clinical progression, most evident in the subcohort of male patients where the placebo group showed more rapid progression.
"It is unfortunate the premature discontinuation of study medication and unanticipated low event rate complicate the interpretation of this trial," said Dr. Wolinsky. "Most sensitivity subcohort analyses supported or strengthened the primary analysis, suggesting a trend toward delaying disease progression with COPAXONE(R)."
COPAXONE(R) is indicated for the reduction of the frequency of relapses in relapsing-remitting MS. The most common side effects of COPAXONE(R) are redness, pain, swelling, itching, or a lump at the site of injection, weakness, infection, pain, nausea, joint pain, anxiety, and muscle stiffness.
COPAXONE(R) (glatiramer acetate injection) is now approved in 42 countries worldwide, including the United States, Canada, Australia, Israel, and all the European countries. In Europe, COPAXONE(R) is marketed by Teva Pharmaceutical Industries Ltd., and Aventis Pharma. In North America, COPAXONE(R) is marketed by Teva Neuroscience.
Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 30 pharmaceutical companies in the world. The company develops, manufactures, and markets generic and branded human pharmaceuticals and active pharmaceutical ingredients. Close to 90 percent of Teva's sales are in North America and Europe. Teva's innovative R&D focuses on developing novel drugs for diseases of the central nervous system.
Teva Pharmaceuticals USA is a subsidiary of Teva Pharmaceutical Industries Ltd. Teva Neuroscience, Inc. is a subsidiary of Teva Pharmaceutical Industries Ltd. Teva Neuroscience, Inc. markets COPAXONE(R).
COPAXONE(R) is a registered trademark of Teva Pharmaceutical Industries Ltd.
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