R&D	Innovative R&D Home Multiple Sclerosis Franchise Other Neurological/Neurodegenerative Diseases Auto-Immune/Inflammatory Diseases Oncology

Other Neurological/Neurodegenerative Diseases

Azilect® (rasagiline mesylate) for Parkinson's Disease

Rasagiline mesylate (Azilect®) is a novel, selective and potent irreversible monoamine oxidase type B (MAO-B) inhibitor for the treatment of Parkinson's Disease (PD) patients, both as monotherapy and as adjunct therapy to levodopa. To date, Azilect® is approved for marketing in the US, Canada, Israel, the EU and Turkey.

Unlike deprenyl, an established drug for PD with a similar mechanism of action, Azilect® is not metabolized to amphetamine derivatives. Its main metabolite, aminoindan, improves motor and cognitive functions in experimental models and may thus contribute to the overall beneficial pharmacological profile of the drug.

Azilect® has demonstrated neuroprotective activity in various in-vitro models. Furthermore, it has shown activity in pre-clinical in-vivo models relevant for depression, stroke, head trauma, hyperactivity syndrome, amyotrophic lateral sclerosis and other neurological diseases. Three phase III studies demonstrated Azilect® efficacy as monotherapy (TEMPO study) and as adjunct therapy to levodopa (PRESTO and LARGO studies). In the TEMPO study, early treatment with Azilect® resulted in less functional decline than when the treatment was delayed for 6 months. These results suggest that the effect of rasagiline on the progression of disability in patients cannot be fully explained by its symptomatic effect and may be due to a disease modifying activity of the drug. A large (over 1000 patients), global, phase IIIb study is currently ongoing to confirm Azilect® has a disease modifying effect in PD (ADAGIO study).

Azilect® development was based on original research performed by scientists from the Rappaport Research Institute, Technion, Haifa, Israel. Teva has acquired the exclusive world-wide license to all intellectual property related to rasagiline.

Teva has signed an agreement for the joint development and marketing of rasagiline for PD in Europe with the Danish pharmaceutical Company, H. Lundbeck A/S.

Selected publications:

Abu-Raya, S. et al.: J. Neuroscience Research (1999); 58:456-463
Parkinson's Study Group (Siderowf A.): Arch. Neurolo. (2002); 59(12):1937-1943
Parkinson's Study Group (Siderowf A.): Arch. Neurolo. (2004); 61:561-566
Rascol, O. et al.: Lancet (2005); 365:947-954

For further information on Azilect: www.azilect.com

Rasagiline Mesylate for Alzheimer's Disease

Rasagiline has shown beneficial activity in experimental Alzheimer's Disease (AD) models. Since its mechanism of action is different from that of all currently approved drugs for this indication, it may be a good candidate for combined treatment with the currently available therapies.

An early Phase II safety study of rasagiline in mild-moderate AD patients has been completed, demonstrating a good safety profile of rasagiline mesylate in this patient population.

A phase II study, in which rasagiline is used as an adjunctive treatment in patients treated with Aricept ®, is currently on-going.

Selected publications:

Speizer, Z. et al: Pharmacol.Biochem. Behav. (1998); 60: 387-393
Huang, W. et al: Eur. J. Pharm. (1999);366: 127-135

Glatiramer Acetate for Amyotrophic Lateral Sclerosis and other neurodegenerative diseases

The development of glatiramer acetate for neurodegenerative diseases is based on concepts discovered and developed by scientists from the Weizmann Institute of Science, Rehovot, Israel.

Glatiramer acetate was tested in various animal models for chronic inflammatory and neurodegenerative diseases, such as optic nerve injury, head trauma, glutamate toxicity, glaucoma and amyotrophic lateral sclerosis (ALS). These studies demonstrated that the immunomodulating activity of the compound results in anti-inflammatory as well as neuroprotective effects. Based on these studies, a Phase II study with glatiramer acetate in ALS patients is now on-going.

Teva has entered into a licensing agreement with the Israeli start-up company, Proneuron, for the world-wide development and commercialization of glatiramer acetate for various neurodegenerative diseases.

Selected publications:

Kipnis J., et.al PNAS (2000); 97 (13) p.7446-7451
Schori H., et al. PNAS (2001); 98 (6) p.3398-3403
Avidan H., et al. Eur. J. of immunol.(2004); 34 : 3434-3445
Angelov DN., et al., Proc Natl Acad Sci U S A. 2003; 100(8): 4790-5

Talampanel for Amyotrophic Lateral Sclerosis and other neurodegenerative disease

Talampanel is an orally active antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) neuronal excitatory glutamate receptor. In pre-clinical studies, talampanel showed activity in epilepsy as well as in various models for neurodegenerative diseases, in which neuronal injury may occur via glutamate excitotoxicity.

A pilot phase II study of talampanel in ALS patients has shown promising results and a larger confirmatory phase II study is now being planned.

Talampanel was discovered at the Institute for Drug Research in Budapest, Hungary and developed by Ivax Research, Inc.

Selected publications:

Chappell AS., Sander JW., Brodie MJ., et. al. A crossover, add-on trial of talampanel in patients with refractory partial seizures. Neurology (2002); 58(11):1680-1682
2. Ramsay R., Fetell M., Bell C: Efficacy in open extension phase of talampanel in refractory partial epilepsy. Neurology (2006);66, Suppl 2, A37