Azilect®

Azilect® (rasagiline tablets) is Teva's second innovative drug, indicated for the treatment of Parkinson's disease, both as initial monotherapy in the early stage of the disease and as an adjunct to levodopa in moderate to advanced stages of the disease. Its development was based on original research performed in the Rappaport Research Institute, Technion, Haifa, Israel. Azilect® is a potent, second-generation, irreversible monoamine oxidase type B (MAO-B) inhibitor with neuroprotective activities demonstrated in various in vitro and in vivo studies. Its beneficial clinical effect, seen in the entire spectrum of the disease, combined with its once-daily dosing, lack of need for titration and high tolerability, allows Azilect® to address significant unmet needs in the treatment of Parkinson's disease.

Azilect® Product Profile

Azilect once daily is efficacious in the treatment of PD as monotherapy in early-disease, providing patients with dual benefit - both symptomatic effect, including motor symptoms, activities of daily living, and quality of life, as well as effect on slowing the clinical progression of the disease. Azilect® also has demonstrated efficacy as an adjunct therapy of PD: symptomatic control of PD and treatment of motor complications in moderate-to-advanced PD patients experiencing motor fluctuations. All effects were demonstrated on top of optimised anti-PD therapy. Azilect® has been proven to be safe and well tolerated in both monotherapy and adjunct therapy in PD patients of all ages, with low incidence of adverse events and low discontinuation rate. In contrast with most other treatments for PD, Azilect® has a simple dosing regimen of one tablet taken once daily at any time, with or without food, and it does not require titration. This combination of simple regimen and very good tolerability contributes to patients' compliance with treatment, and therefore to the success of treatment.

Clinical Development of Azilect®

Azilect® has demonstrated efficacy and safety in three pivotal studies that included over 1,500 patients with Parkinson´s disease at different stages of the disease.

TEMPO - demonstrated the clinical efficacy of Azilect as monotherapy in early PD patients. Patients were also followed through an open-label long-term extension phase of over 6 years, confirming the safety and efficacy of early treatment with Azilect in the long term.
LARGO - conducted in Europe, Israel and Argentina, and it's results showed high efficacy of Azilect as an adjunct therapy, given on top of other anti PD medications, with entacapone as an active comparator.
PRESTO - performed in North America, results confirming the clinical efficacy of Azilect as adjunct therapy in moderate-to-advanced PD patients.

Based on the results of these trials , Azilect was granted marketing approvals in the US, Canada, the EU , Israel, and some additional countries. Until recently, no treatment had ever been proven to slow the progression of Parkinson´s disease. The pharmacological strategy for the management of Parkinson´s disease has involved the use of drugs to reduce the motor symptoms of the disease and to otherwise bring symptomatic relief to patients. Based on the findings of the TEMPO and its open extension results, as well as the broad pre-clinical evidence for the neuroprotective effects of rasagiline, Teva initiated the ADAGIO (Attenuation of Disease progression with Azilect® Once-daily) study with AZILECT in November 2005.

The ADAGIO study

In June 2008, Teva announced the positive results of the ADAGIO study that was designed to explore the disease modifying effects of Azilect by slowing the rate of disease progression. ADAGIO is one of the largest ever trials in early PD patients. The study recruited 1176 very early PD patients in 14 countries in Europe, North America, Israel and Argentina. The trial used a novel delayed-start design with a 9 month, double-blind, placebo-controlled phase, and a second 9-month active treatment phase comparing the early-start cohort with the delayed-start cohort. AZILECT 1mg, the marketed dose worldwide, met all three endpoints of the primary analysis in a hierarchal manner, demonstrating that Azilect has a positive effect on slowing the clinical progression of PD. Slowing disease progression is currently one of the major unmet needs in PD, and Azilect is the first drug to show such an effect in a well designed prospective clinical study.

Marketing and Distribution

Azilect® was first launched in Israel, in March 2005, and shortly thereafter, in the first EU countries, the UK and Germany. In the USA, Azilect® was launched in July 2006. Presently, Azilect® is available in 32 countries. Teva has a long-term agreement for the joint development and marketing of Azilect in Europe and some additional markets with H. Lundbeck A/S. In North America, Azilect® is marketed by Teva's wholly-owned subsidiary Teva Neuroscience (www.tevaneuro.com).

About Parkinson's Disease

Parkinson's disease (PD) is a degenerative disorder of the central nervous system that impairs the sufferer's motor skills and speech. PD is both a chronic and progressive illness, which results in a marked decrease in the health-related quality of life of patients and their caregivers and places a tremendous economic burden on society. An estimated four million patients are affected by this chronic disease worldwide, which typically occurs at a late age, affecting approximately 1% of the population over the age of 65. 1 in 20 people diagnosed with PD is younger than 40 years.

Selected Publications

TEMPO: Parkinson's Study Group (Siderowf A.): Arch. Neurolo. (2002); 59(12):1937-1943
TEMPO delayed-start: Parkinson's Study Group (Siderowf A.): Arch. Neurolo. (2004); 61:561-566
LARGO: Rascol, O. et al.: Lancet (2005); 365:947-954
PRESTO: Parkinson's Study Group; Arch Neurol. (2005); 62:241-248.
ADAGIO: Rationale, design, and baseline characteristics. Olanow CW et al: Mov Disord 2008; 23 (15):
2194 - 2201.

For additional information about Azilect®, please see the product website: www.Azilect.com.