COPAXONE® Significantly Decreases Disease Activity in Patients Who Switched from Interferon Beta (INFb) Due to Development of Neutralizing Antibodies

Relapsing-remitting multiple sclerosis Patients Experience Significantly Extended Time to First Relapse Compared to NAbs-Positive IFNb Patients

JERUSALEM--(BUSINESS WIRE)--Patients treated with interferon beta (IFNb) who have experienced loss of efficacy due to the development of neutralizing antibodies, had a significant delay in time to first relapse (p=0.0389) following switch to COPAXONE®. In addition, patients who were switched to COPAXONE® experienced reduction in mean annual relapse rate compared to pre-IFNb treatment. Results from this retrospective comparative study were presented at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Prague.

“The development of NAbs occurs in up to 30 percent of RRMS patients treated with IFNb therapy and has been shown to impair the therapeutic effectiveness of IFNb therapies,” said Dr. Antonio Bertolotto, Centro Riferimento Regionale Sclerosi Multipla (CReSM) and Laboratorio di Neurobiologia Clinica, Ospedale Universitario San Luigi, Orbassano, Italy. “In our MS Center patients with NAbs persistently positive and without IFNb biological activity measured by MxA (Myxovirus A) mRNA (Messenger Ribonucleic Acid) and with a Relapse Rate/year of 1 or less where switched to COPAXONE®. These data suggest that physicians should discontinue IFNb treatment in patients who test positive for NAbs and that they should strongly consider switching patients to COPAXONE®, as it improves clinical measures of disease activity”.

About the Study

The retrospective comparative analysis evaluated changes in relapse rate, proportion of relapse-free patients and time to first relapse between IFNb and COPAXONE® in NAbs-positive patients who were switched to COPAXONE®. Patients evaluated in the analysis (n=19) were identified as having persistent NAbs positivity (at least 2 months consecutive 3 months apart sera), abolished bioactivity of IFNb therapy, as measured by MxA mRNA, low disease activity during IFNb treatment (one or fewer relapse in the last year of IFNb treatment) and at least 12 months of follow up after COPAXONE® introduction.

The mean annualized relapse rate in pre-IFNb, IFNb NAbs-negative, IFNb NAbs-positive and COPAXONE® (glatiramer acetate injection) treatment periods were respectively 0.98, 0.1, 0.32, 0.21 (p<0.001 for pre-IFNb treatment period versus each other treatment period; p=NS for other group analyses). The time to first relapse was significantly different among the IFNb NAbs-negative, IFNb NAbs-positive and COPAXONE® treatment periods, with a significant difference between the IFNb NAbs-positive and COPAXONE® treatment periods (50th percentile: 17.8 versus 37.9 months; 75th percentile: 6.9 versus 12.9 months; p=0.0389).

For additional details on the study design and results, please refer to the poster “Glatiramer acetate reduces disease activity in NAbs to IFNb-positive patients,” by M. Capobianco, A. Sala, S. Malucchi, M. Caldano, A. Di Sapio, F. Sperli, A. Oggero, F. Marnetto, P. Valentino, L. Granieri, F. Gilli, A. Bertolotto.

About MS

Multiple Sclerosis (MS) is the leading cause of neurological disability in young adults. It is estimated that 400,000 people in the United States are affected by this disease, and that over one million people are affected worldwide. MS is a progressive, demyelinating disease of the central nervous system affecting the brain, spinal cord and optic nerves.

Patients with MS may experience physical symptoms and/or cognitive impairments, including weakness, fatigue, ataxia, physical dysfunction, bladder and bowel problems, sensory effects, and visual impairment. MS also has a significant impact on the sufferers' social functioning and overall quality of life.

About COPAXONE®

Current data suggest COPAXONE® (glatiramer acetate injection) is a selective MHC (Major Histocompatability Complex) class II modulator. COPAXONE® is indicated for the reduction of the frequency of relapses in RRMS. The most common side effects of COPAXONE® are redness, pain, swelling, itching, or a lump or an indentation at the site of injection, weakness, infection, pain, nausea, joint pain, anxiety, and muscle stiffness.

COPAXONE® is now approved in 47 countries worldwide, including the United States, Canada, Mexico, Australia, Israel, and all European countries. In Europe, COPAXONE® is marketed by Teva Pharmaceutical Industries Ltd. and sanofi-aventis. In North America, COPAXONE® is marketed by Teva Neuroscience, Inc.

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. Over 80 percent of Teva’s sales are in North America and Europe.

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.

About Teva

Teva Pharmaceutical Industries Ltd. (NASDAQ: TEVA), 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. Over 75 percent of Teva's sales are in North America and Europe.

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 extent to which Teva may obtain U.S. market exclusivity for certain of its new generic products and regulatory changes that may prevent Teva from utilizing exclusivity periods, competition from brand-name companies that are under increased pressure to counter generic products, or competitors that seek to delay the introduction of generic products, the impact of consolidation of our distributors and customers, 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®, Neurontin®, Lotrel®, and Famvir®, the effects of competition on our innovative products, especially Copaxone® 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, our ability to achieve expected results though our innovative R&D efforts, Teva’s ability to successfully identify, consummate and integrate acquisitions, potential exposure to product liability claims to the extent not covered by insurance, dependence on the 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, supply interruptions or delays that could result from the complex manufacturing of our products and our global supply chain, environmental risks, fluctuations in currency, exchange and interest rates, 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.

Contacts
Teva Pharmaceutical Industries Ltd.
Dan Suesskind, 972-2-941-1717
Chief Financial Officer
or
Teva Pharmaceutical Industries Ltd.
Teva North America
George Barrett, 215-591-3030
Corp. Exec. V.P. - Global Pharmaceutical Markets
Chief Executive Officer
or
Teva Pharmaceutical Industries Ltd.
Teva North America
Liraz Kalif / Kevin Mannix, Investor Relations
972-3-926-7281
215-591-8912
Website: www.tevapharm.com

Large Study Shows that Presence of Neutralizing Antibodies Did Not Predict Clinical Response to Betaseron Treatment

WAYNE, N.J., April 02, 2007 /PRNewswire/ -- Berlex, Inc., a U.S. affiliate of Bayer Schering Pharma AG, Germany, announced today the results of a retrospective study demonstrating that the presence of neutralizing antibodies (NAbs) that can develop in response to Betaseron(R) (interferon beta-1b) therapy did not predict clinical response in patients with multiple sclerosis (MS).(1) The study looked at data from over 6,600 patients across three continents. It is the largest dataset ever analyzed on the relevance of NAbs to interferon beta therapy. The results were published in the March issue of The Journal of International Medical Research.


"This study confirms that NAbs, which develop in response to Betaseron therapy, tend to disappear over time and provides important evidence that the presence of NAbs in these patient populations was not associated with a poor clinical response to treatment." said Dr. Douglas Goodin, lead author of the article and Professor of Neurology, University of California, San Francisco. "While it is unclear how these findings might apply to other beta interferon therapies, these data underscore the fact that decisions regarding Betaseron treatment should be based on the clinical circumstances of the individual patient and not solely on the basis of their NAb status."

NAbs are antibodies that may attach themselves to an injected protein drug, such as beta interferon therapy, thereby potentially inhibiting its biological activity. All immunomodulating therapies for MS may cause the development of NAbs in a varying portion of patients, but there is controversy in the medical community about the role NAbs may or may not play in a patient's response to therapy.

"This study reinforces expert recommendations that treatment decisions should be based on a patient's overall response to therapy and not on the actual or potential presence of neutralizing antibiodies," said Darlene Jody, M.D., Executive Vice President, Specialized Therapeutics, Bayer Schering Pharma AG, Germany. "When treating MS, especially from the first event, patients and prescribers can continue to rely on the proven efficacy and safety of Betaseron."

The published study addressed the clinical impact of NAbs to Betaseron therapy in an office-based or "real world" setting. These results are in line with the clinical practice guidelines recently published by the American Academy of Neurology.(2) Since the development of NAbs is specific to each medication, it is unclear how these findings for Betaseron might apply to other beta interferons.

About the Study

The study reviewed the NAb status of 6,698 Betaseron patients from North America (n=2010), Europe (n=2417) and Australia (n=2271) using the myxovirus protein A assay (MxA). The prevalence of persistently high neutralizing antibodies in the Australian cohort, which included patients regardless of clinical response to Betaseron, was 37%. This finding was similar to the reported incidence seen in Betaseron clinical trials. The incidence of persistently high NAbs in the European and North American groups, however, was only 28% and 21% respectively even those these patients were pre-classified as having a "poor clinical response" to therapy. Since the patients known to be poor responders were more often NAb negative than the general population, the study concluded that persistent, high NAb status was not a key predictor of clinical response to therapy.

Data for the study were collected during a six-year period (1996-2002). Most of the NAb testing (73%) was performed within the first three years of treatment, when patients are thought to be at the greatest risk of developing NAbs. Patients in the study had MS for an average seven to 10 years at the time of testing.

About Betaseron

Betaseron (Interferon beta-1b) is indicated for the treatment of relapsing forms of multiple sclerosis to reduce the frequency of clinical exacerbations. Patients with multiple sclerosis in whom efficacy has been demonstrated include patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.

The most commonly reported adverse reactions are lymphopenia, injection- site reaction, asthenia, flu-like symptom complex, headache and pain. Gradual dose titration and use of analgesics during treatment initiation may help reduce flu-like symptoms. Betaseron should be used with caution in patients with depression. Injection-site necrosis has been reported in 5% of patients in controlled trials. Patients should be advised of the importance of rotating injection sites. Female patients should be warned about the potential risk to pregnancy. Cases of anaphylaxis have been reported rarely. See "Warnings," "Precautions," and "Adverse Reactions" sections of full Prescribing Information.

About Berlex

Berlex, Inc. is a U.S. affiliate of Bayer Schering Pharma AG, Germany, which is a subsidiary of Bayer AG. Bayer AG is one of the world's leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Diabetes Care, and Pharmaceuticals divisions. The US Pharmaceuticals division comprises the following business units: Women's Healthcare, Diagnostic Imaging, Specialized Therapeutics, Hematology/Cardiology, and Oncology. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

Certain statements in this press release that are neither reported financial results nor other historical information are forward-looking statements, including but not limited to, statements that are predictions of or indicate future events, trends, plans or objectives. Undue reliance should not be placed on such statements because, by their nature, they are subject to known and unknown risks and uncertainties and can be affected by other factors that could cause actual results and Berlex's plans and objectives to differ materially from those expressed or implied in the forwardlooking statements. Berlex, Inc. undertakes no obligation to update publicly or revise any of these forward-looking statements, whether to reflect new information or future events or circumstances or otherwise.

(1) Goodin, DS, Hurwitz B, Noronha A.. Neutralizing Antibodies to Interferon beta-1b are Not Associated with Disease Worsening in Multiple Sclerosis. J Int Med Res. 2007; 35: 173-187.

(2) Goodin DS et al. Neutralizing antibodies to interferon beta: Assessment of their clinical and radiographic impact: An evidence report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2007; 68: 977-984.

CONTACT: Marcy Funk of Berlex, +1-973-305 5385

Web site: http://www.berlex.com//

Terms and conditions of use apply
Copyright © 2007 PR Newswire Association LLC. All rights reserved.
A United Business Media Company