Healthcare Industry News:  Teva Neuroscience 

Biopharmaceuticals Neurology

 News Release - May 4, 2007

COPAXONE(R) Treatment over Two Years after Short Term Induction with Mitoxantrone Provided Sustained Benefits to Active Relapsing-Remitting Multiple Sclerosis Patients

Increased Efficacy on MRI and Clinical Outcomes Achieved at 15 Months Was Sustained for 24 Months in Follow-up Study

KANSAS CITY, Mo.--(HSMN NewsFeed)--New data have demonstrated that relapsing-remitting multiple sclerosis (RRMS) patients treated with COPAXONE® (glatiramer acetate injection) following brief immunosuppression with mitoxantrone experienced a 90 percent reduction in magnetic resonance imaging (MRI)-monitored disease activity compared to their baseline. These benefits were achieved early on and were sustained throughout the 24-month study period. These long-term data were consistent with the 15-month initial results of this study, previously presented at an international meeting on multiple sclerosis (MS), which demonstrated that the induction treatment strategy was more effective than COPAXONE® alone on reducing relapses and MRI measures of disease activity (p=0.0147). Treatment with COPAXONE® after induction with mitoxantrone remained safe and effective throughout the treatment period.

These new findings were presented at the 59th Annual Meeting of the American Academy of Neurology (AAN) along with new confirming MRI findings from the 15-month study, which showed that the decreases in clinical and MRI markers of disease activity, were accompanied by favorable effects on disease burden and irreversible brain tissue damage as shown by significant decreases in the accumulation of lesion load, and significant reduction in the proportion of lesions evolving into chronic black holes.

"This combination therapy is emerging as a promising treatment option for patients who have active RRMS, or who are not responding optimally to traditional first-line therapies," said Tim Vollmer, M.D., Director, Neuroimmunology Program, Barrow Neurological Institute at St. Joseph's Hospital and Medical Center and the primary investigator in this study. "This study builds on earlier studies that demonstrate the effect of COPAXONE® on disease activity and inflammation in the central nervous system of RRMS patients," he added.

Data analysis surrounding the mode of action of this novel treatment strategy was also presented at the AAN, in which researchers attributed the benefit of the combination of therapies to the combined anti-inflammatory effect of COPAXONE® and mitoxantrone.

"These data shed new light on the concept of treating MS by first suppressing the auto-aggressive immune system with an immunosuppressant, and then favorably modifying its activity with an immunomodulator such as COPAXONE®," said Amit Bar-Or, M.D., FRCPC, assistant professor, Director of the Experimental Therapeutics at the Montreal Neurological Institute (MNI) and primary investigator of the immunological study.

About the Analyses

The analysis, Reductions in MRI Disease Activity and Relapse Rates Observed after Induction of Short-term Immunosuppression with Mitoxantrone Followed by Long-term Glatiramer Acetate (GA) Are Maintained at 24 Months in Patients with Relapsing Remitting Multiple Sclerosis (RRMS), determined that the increased efficacy and the safety observed at 15 months with COPAXONE® after brief mitoxantrone therapy was maintained with continued COPAXONE® at 24 months. The original study included RRMS patients (n=40), ages 18-55, who had at least one Gd-enhancing lesion at the time of the screening MRI and an Expanded Disability Status Scale (EDSS) score of <= 6.5. Brain MRIs were performed at screening and months six, nine, 12 and 15.

The abstract is accessible online at: &terms. (Due to its length, this URL may need to be copied/pasted into your Internet browser's address field. Remove the extra space if one exists.)

Patients were randomized to receive 3 monthly intravenous (IV) infusions of mitoxantrone (36 mg/m(2) total) followed by a 2-week washout, then COPAXONE® 20 mg/d for 12.5 months (n=21) or COPAXONE® 20 mg/d alone (n=19) for 15 months.

In the 24-month follow-up of continued COPAXONE® therapy, primary outcomes were safety and tolerability. Secondary outcomes included changes from baseline to 24 months in Gd-enhancing lesions, relapses and EDSS.

Thirty patients entered the extension study. Analyses at 15 months indicated a 70 percent reduction in Gd-enhancing lesions in the mitoxantrone-COPAXONE® group vs COPAXONE® group (risk ratio=0.30, 95 percent CI (0.11-0.86), p=0.0147). These effects appeared to be sustained.

The analysis, Reductions in Gd Enhancing Lesions Observed with Glatiramer Acetate Following a Brief and Low Dose Course of Mitoxantrone in Patients with Relapsing Remitting Multiple Sclerosis (RRMS) Are Paralleled by Favorable Effects on MRI Markers of Disease Burden and Black Hole Evolution, evaluated whether effects on MRI markers of disease burden and tissue damage corroborate the beneficial effects on disease activity observed 15 months after initiating COPAXONE® therapy with a brief, low dose induction with mitoxantrone.

The abstract is accessible online at: &terms. (Due to its length, this URL may need to be copied/pasted into your Internet browser's address field. Remove the extra space if one exists.)

This analysis compared patients who were randomized to receive either three months of induction treatment with mitoxantrone followed by COPAXONE® for 12 months (n=21) or COPAXONE® alone (n=19) for 15 months.

The further MRI analyses showed that the reductions in Gd-enhancing lesions and relapse activity seen at 15 months were accompanied by significant differences favoring the mitoxantrone-COPAXONE® group in the change from baseline in the volume of T2-weighted lesions (p=0.0139), the volume of T1-weighted lesions (p=0.0303) and the proportion of Gd-enhancing lesions that evolved into chronic black holes at month 15 (p=0.0023).

The analysis, "Tracking In Vivo Immune Modulation in MS Patients Treated with Glatiramer Acetate (GA) Alone, or with GA Preceded by Mitoxantrone, Provides Novel Insights into the Mode of Action of Therapeutic Strategies That Combine Immune Suppression and Immune Deviation" examined the mechanism of action of the combination of COPAXONE® and mitoxantrone versus treatment with COPAXONE® alone.

The abstract is accessible online at: &terms. (Due to its length, this URL may need to be copied/pasted into your Internet browser's address field. Remove the extra space if one exists.)

Findings of this immunological analysis comparing patients who received either 3 months of induction treatment with mitoxantrone followed by COPAXONE® for 12 months or COPAXONE® alone for 15 months, was designed to determine whether the improved clinical and MRI outcomes reflect an enhanced capacity for COPAXONE®-mediated Th2 shift following immune suppression. Researchers serially measured patients' (n=21) serum for COPAXONE®-reactive antibodies (Total IgG: IgG1, IgG2, IgG3, IgG4) by ELISA (enzyme-linked immunosorbant assay). The relationship between IgG1 and IgG4 COPAXONE®-reactive antibodies has been determined to be a useful marker of COPAXONE®-mediated Th2 shift.

Researchers concluded that induction with mitoxantrone appears to partially reduce and/or delay the IgG1 to IgG4 switch characteristic of the Th2 shift. This information, coupled with MRI measures of disease activity suggest the enhanced efficacy of COPAXONE®-mitoxantrone over COPAXONE® alone is not due to an enhanced Th2-shift but rather reflects combined anti-inflammatory effects of COPAXONE® and mitoxantrone.


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, 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., which is a subsidiary of Teva Pharmaceutical Industries Ltd (NASDAQ:TEVA ). COPAXONE® 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.

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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® and Neurontin®, 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.

Source: Teva Neuroscience

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