Tuesday, February 27, 2007
Initial Analysis of the Full Study Cohort Showed Treatment Did Not Demonstrate Significant Effect on Primary Endpoint of Accumulated Delay to Disabili
KANSAS CITY, Mo.--(BUSINESS WIRE)--Feb. 27, 2007--Data from the full cohort of the PROMiSE study showed that treatment with COPAXONE(R) (glatiramer acetate injection) did not reach a significant effect on the primary endpoint of accumulated delay to disability versus placebo in the entire population of patients with primary progressive multiple sclerosis (PPMS) (39.6 percent versus 45.2 percent respectively, p = 0.1753). However, post-hoc analyses demonstrated that COPAXONE(R) significantly delayed time to progression of accumulated disability in male patients in the study (n=455) who received treatment versus those who received placebo (p = 0.0193). Results of the randomized, double-blind study of over 900 patients were published in a recent issue of Annals of Neurology.
In the study, treatment differences in male patients emerged early and were maintained over time; 61.6 percent of male patients receiving COPAXONE(R) remained progression-free as opposed to only 49.1 percent of those in the placebo group. Data from the entire population also showed that COPAXONE(R) reduced the burden and activity of lesions in the brain as measured by T2-weighted and gadolinium (Gd)-enhanced magnetic resonance images (MRI).
"COPAXONE(R) in this trial demonstrated a trend towards slowed disease progression versus those patients left untreated, which was only statistically significant in male patients in the post hoc analysis," said Dr. Jerry Wolinsky, Bartels Family and Opal C. Rankin Professor of Neurology, interim Dean, The University of Texas Health Center at Houston and the lead investigator of the trial.
PPMS is a degenerative form of multiple sclerosis (MS), a chronic, progressive, degenerative disorder that affects nerve fibers in the brain and spinal cord. PPMS patients experience near continual progression of disease over their lifetimes without any discernable relapses or remission of neurologic disability. Compared with relapsing-remitting multiple sclerosis (RRMS) patients, PPMS affects a higher proportion of men than women, and data suggest that men with PPMS may progress faster than women. Currently, there are no proven effective treatments for PPMS.
"The results of the PROMiSe study may warrant additional trials surrounding the effect of COPAXONE(R) on PPMS, given the fact that there are no other treatments currently available. The lack of a statistically significant treatment response in women in the study does not mean that COPAXONE(R) doesn't hold promise for further study in this population," said Wolinsky.
About the Study
The PROMiSe trial followed 943 patients who were randomized for treatment with COPAXONE(R) (n=627) or placebo (n=316) in a two-to-one ratio. A pre-planned 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 medication was discontinued.
Despite the termination of the PROMiSe study, patients were offered the opportunity to continue to be followed. An intent-to-treat (ITT) analysis at three years was conducted to determine whether different outcomes occurred in subgroups of patients because of an unexpected on-trial slow rate of disease progression among participants and abbreviated exposure to COPAXONE(R) (glatiramer acetate injection) therapy, both of which made detecting a treatment effect challenging. The post-hoc analysis demonstrated a trend toward delaying disease progression which was significant in the male subgroup of patients (n=455) who experienced a slowing disease progression to sustained disability in favor of COPAXONE(R). Post-hoc analyses are intended to re-examine an existing data set to determine potential patterns or trends that may not have been apparent based on the initial review of the data as set forth by the study design. 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.
"Currently there have been no clinical trials in PPMS as large or comprehensive as the PROMiSe trial, nor are there any comparable sized studies currently being undertaken," said Wolinsky. "Because of this trial, we probably know more about the natural history of PPMS than we did before, which is of immeasurable value to the field."
Initial data from the PROMiSE trial were previously reported at the 2004 Annual Meeting of the American Academy of Neurology.
Current data suggests COPAXONE(R) (glatiramer acetate injection) is a selective MHC class II modulator. COPAXONE(R) is indicated for the reduction of the frequency of relapses in RRMS. The most common side effects of COPAXONE(R) are redness, pain, swelling, itching, a lump or an indentation at the site of injection, weakness, infection, pain, nausea, joint pain, anxiety, and muscle stiffness.
COPAXONE(R) is now approved in 44 countries worldwide, including the United States, Canada, Mexico, Australia, Israel, and all European countries. In Europe, COPAXONE(R) is marketed by Teva Pharmaceutical Industries Ltd. and sanofi-aventis. In North America, COPAXONE(R) is marketed by Teva Neuroscience, Inc., which is a subsidiary of Teva Pharmaceutical Industries Ltd (NASDAQ:TEVA). COPAXONE(R) is a registered trademark of Teva Pharmaceutical Industries Ltd.
Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 20 pharmaceutical companies in the world and is the leading generic pharmaceutical company. The company develops, manufactures and markets generic and innovative human pharmaceuticals and active pharmaceutical ingredients, as well as animal health pharmaceutical products. 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.
See additional important information at http://www.copaxone.com/pi/index.html or call 1-800-887-8100 for electronic releases. For hardcopy releases, please see enclosed full prescribing information.
Safe Harbor Statement under the U. S. Private Securities Litigation Reform Act of 1995: This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements are based on management's current beliefs and expectations and involve a number of known and unknown risks and uncertainties that could cause Teva's future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to Teva`s ability to successfully develop and commercialize additional pharmaceutical products, the introduction of competing generic equivalents, the competition from brand-name companies that are under increased pressure to counter generic products, or competitors that seek to delay the introduction of generic product, Teva's ability to generate revenues and profits closely tied to our success in obtaining U.S. market exclusivity for generic products, the impact of consolidation of our distributors and customers, regulatory changes that may prevent Teva from utilizing exclusivity periods, potential liability for sales of generic products prior to a final resolution of outstanding patent litigation, including that relating to the generic versions of Allegra(R), Neurontin(R) and Wellbutrin XL(R) , the effects of competition on our innovative products, especially Copaxone(R) sales, the impact of pharmaceutical industry regulation and pending legislation that could affect the pharmaceutical industry, the difficulty of predicting U.S. Food and Drug Administration, European Medicines Agency and other regulatory authority approvals, the regulatory environment and changes in the health policies and structures of various countries, Teva's ability to successfully identify, consummate and integrate acquisitions, potential exposure to product liability claims which are not covered by insurance, dependence on effectiveness of our patents and other protections for innovative products, significant operations worldwide that may be adversely affected by terrorism, political or economical instability or major hostilities, the difficulty of complex manufacturing of our products and supply delays, environmental risks, fluctuations in currency, exchange and interest rates, operating results and other factors that are discussed in Teva's Annual Report on Form 20-F and its other filings with the U.S. Securities and Exchange Commission. Forward-looking statements speak only as of the date on which they are made and the Company undertakes no obligation to update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.
This is a news service of Thomson Business Intelligence Service ©2006. This content is for your personal use only, subject to Terms and Conditions. No redistribution allowed.