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Multiple Sclerosis Franchise

Copaxone® (glatiramer acetate for injection)

Copaxone® (glatiramer acetate for injection) is the first non-interferon drug approved for the treatment of relapsing-remitting multiple sclerosis (R-R MS). Copaxone® is also the first Israeli-developed innovative drug to receive FDA approval for marketing in the United States. It is also approved in Canada, the EU, Israel, Switzerland, Australia and numerous other markets.

Originating from research at the Weizmann Institute of Science in Rehovot, Israel, Teva succeeded in developing this extraordinarily complex molecule into a very successful pharmaceutical product: It has a dual mechanism of action affecting both the inflammatory and neurodegenerative aspects of the disease and also a positive effect on re-myelination. This results in long-term efficacy coupled with a very good long-term safety profile.

Efforts are continuing towards the launch of Copaxone® in additional international markets, as well as towards broadening its indications and usage within the MS population. To this end, an extensive Medical Operating plan, consisting of various clinical trials, is on-going. This includes studies with a higher dose of glatiramer acetare ( 40 mg - the FORTE study); studies in Clinically Isolated Syndrome patients (the PreCISe study) as well as numerous combination and induction protocols, in which glatiramer acetate is given together with or following another active product. Recent results from some of the latter studies reveal a very good effect of Copaxone® in highly active patients.

Teva is collaborating with Aventis in the marketing and co-promotion of Copaxone® for MS in all territories except for North America, where marketing is performed by the fully-owned Teva subsidiary, Teva Neuroscience (TN) and for Israel, where marketing is performed by Teva Israel.

Selected publications:

Johnson, K. et al.:Neurology (1995); 45: 1268-1276
Johnson, K. et al.:Neurology (1998); 50: 701-708
Comi,G. and Filippi,M.:Ann. Neurol. (2001); 49:290-297
Riven-Kreitman R. and Blanchette F., Multiple Sclerosis (2004);10:S81-S89
Johnson KP, Ford CC, Lisak RP, Wolinsky JS. Neurologic consequence of delaying glatiramer acetate therapy for multiple sclerosis: 8-year data. Acta Neurol Scand. (2005); Jan;111(1):42-7.
Johnson KP, Brooks BR, Ford CC, Goodman AD, Lisak RP, Myers LW, Pruitt AA, Rizzo MA, Rose JW, Weiner LP, Wolinsky JS. Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in a six-year organized multiple sclerosis trial. Mult Scler. (2003); Dec;9(6):585-91.
Clive Hawkins, FRCP, Massimo Filippi, MD, and Nicola De Stefano, MD PhD (and the 9011 study group) Short-Term Combination of Glatiramer Acetate with IV Steroid Treatment Preceding Treatment with GA Alone Is Associated with early Suppression of MRI-disease activity in Patients with Relapsing Remitting Multiple Sclerosis (2007) submitted
Ramtahal J, Jacob A, Das K, Boggild M. Sequential maintenance treatment with glatiramer acetate after mitoxantrone is safe and can limit exposure to immunosuppression in very active, relapsing remitting multiple sclerosis (2006) J Neurol.;253(9):1160-4
M. Rovaris, J. Cohen, A. Goodman, G. Comi, M. Filippi on behalf of the 9006 Study Group Results of a randomized, double-blind, parallel group study assessing safety and efficacy of 40mg vs 20mg glatiramer acetate on MRI-measured disease activity in relapsing-remitting MS (2006) abstract ENS

Laquinimod

Laquinimod is a novel synthetic, orally bio-available, immuno-modulatory compound, licensed by Teva from the Swedish company, Active Biotech. It has demonstrated impressive efficacy in both acute and chronic experimental autoimmune encephalomyelitis (EAE) models and in non-clinical models of other autoimmune diseases, such as rheumatoid arthritis and insulin-dependent diabetes.

A pilot ,6-month, phase II study in subjects with relapsing MS demonstrated that daily treatment with 0.3 mg laquinimod is effective in decreasing the number of active lesions in the brain (using triple dose of Gd+) and is well -tolerated. A second , 9-month phase II study, using a higher dose has been recently completed, showing that a 0.6 mg daily dose has a statistically significant effect on decreasing the number of active lesions in the brain (using single dose Gd+), as well as a clear trend of reducing the number of clinical relapses. The Phase III program is now in preparation.

Selected publications:

Brunmark C. et al (2002); J Neuroimmunology ; 130 : 163-172
Polman C. et al (2005); Neurology ; 64: 987-91