Teva and Lundbeck announce New England Journal of Medicine publication of landmark ADAGIO study with Azilect® in Parkinson’s disease

Results of early treatment with AZILECT® 1 mg/day tablets consistent with disease-modifying effect

24th September 2009. Teva and Lundbeck announce that the results of the ADAGIO trial were published online today by the New England Journal of Medicine. Patients who received Azilect® (rasagiline) 1mg/day at the start of the study (early-start group) experienced significantly superior benefit over time compared with those who started treatment with Azilect® 1mg/day nine months later (delayed-start group). 1

Professor Olivier Rascol, Department of Clinical Pharmacology, University Hospital, Toulouse, France and ADAGIO co-principal investigator, stated, “The results of the ADAGIO study provide novel data to support the use of AZILECT® 1mg daily as initial treatment of patients with Parkinson’s disease. The ADAGIO study, which utilized a novel trial design with three primary endpoints, suggests that the drug has a positive impact on slowing the progression of patients’ disability, beyond its already known symptomatic benefit.”

The New England Journal of Medicine is the world’s most influential medical journal, recognised for the high scientific standards, novelty and importance of its content. Every year it receives over 5,000 scientific articles of which only a small minority are selected for publication.

Azilect® is the first and only Parkinson’s disease treatment to succeed in a prospective delayed-start study, a trial design specifically developed to test for disease-modifying effects. The results from the ADAGIO study also reconfirm the previously demonstrated symptomatic efficacy of Azilect®.2 The good safety profile of Azilect® seen in the ADAGIO study was in line with previous clinical experience with Azilect®.2

The primary analysis of the ADAGIO study included three hierarchical endpoints based on Total-UPDRS (Unified Parkinson’s Disease Rating Scale) scores. Azilect® 1 mg/day early-start met all endpoints of the primary analysis. Rasagiline 2 mg/day early-start did not meet the second step of the primary analysis as there was no significant difference in UPDRS score between baseline and week 72. Based on the hypothesis that there may have been a masking of the disease-modifying effect with the 2mg dose in patients with milder impairment, the authors conducted a post-hoc analysis on the sub-group of patients with highest baseline UPDRS – the upper quartile. This analysis showed significant results for the 2 mg dose as well as for the 1mg dose for all three primary endpoints.

As Parkinson’s disease is a chronic progressive illness, it is important to have a long-term perspective of a treatment’s impact on its evolution. The authors of the New England Journal of Medicine article address this aspect by concluding that it will be important to see if the benefits seen after 18 months will endure and translate into reduced cumulative disability. An extension of the ADAGIO study is presently underway to address this need.

About the ADAGIO study
ADAGIO was an 18-month randomised, multi-centre, double-blind, placebo-controlled, parallel-group study prospectively examining rasagiline’s potential disease-modifying effects in 1,176 patients with early, untreated Parkinson’s disease. Patients from 129 centres in 14 countries were randomised to early-start treatment (72 weeks rasagiline 1 or 2 mg once daily) or delayed-start treatment (36 weeks placebo followed by 36 weeks rasagiline 1 or 2 mg once daily). The primary analysis of the trial was based on change in total UPDRS (Unified Parkinson’s Disease Rating Scale - the most commonly used rating scale to assess Parkinson’s disease status) and included three hierarchal endpoints: slope superiority of rasagiline over placebo in the placebo-controlled phase, change from baseline to week 72, and non-inferiority of early-start vs. delayed-start slopes during weeks 48-72 of the active treatment phase. Rasagiline 1mg met all 3 primary endpoints: less deterioration in UPDRS points/week in early start than placebo between weeks 12 and 36 (early-start=0.09±0.02, placebo= 0.14±0.01; P=0.01); less worsening of early start than delayed-start in UPDRS score between baseline and week 72 (early-start=2.82±0.53, delayed-start=4.50±0.56; P=0.02), and non-inferiority of early start to delayed-start in deterioration in UPDRS points/week between weeks 48 and 72 (early-start=0.085±0.02, delayed-start=0.085±0.02; P<0.001).

ADAGIO is one of the largest studies ever conducted in Parkinson’s disease. It used the delayed-start design to distinguish between the symptomatic and disease-modifying effects of Azilect®. ADAGIO is the first study in PD to utilize slope analysis, which is the gold standard for measuring the longitudinal effects of a drug. With a mean disease duration of 4.5 (SD 4.6) months and baseline UPDRS-Total score of 20.4 (SD 8.5), the ADAGIO patient population is one of the earliest Parkinson’s disease stages ever to be studied in a large randomised controlled trial.3

About Azilect®
Azilect® (rasagiline) 1mg tablets are indicated for the treatment of the signs and symptoms of Parkinson’s disease both as initial therapy alone and to be added to levodopa later in the disease. Azilect® is currently available in 37 countries, including the US, Canada, Israel, Mexico, and all of the EU countries, where it is marketed by Teva and Lundbeck as part of a long-term strategic alliance between the two companies.

About Parkinson’s disease
Parkinson’s disease is an age-related degenerative disorder of the brain. Symptoms may include: tremor, stiffness, slowness of movement and impaired balance. An estimated four million people worldwide suffer from the disease, which usually affects people over the age of 60.

References
1. Olanow CW et al. A double-blind delayed start trial of rasagiline in Parkinson’s disease. N Engl J Med 2009;361:1268-78
2. Parkinson Study Group. A controlled trial of rasagiline in early Parkinson’s disease. Arch Neurol 2002;59:1937-1943
3. Olanow CW et al. A randomized, double-blind, placebo-controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson’s disease (the ADAGIO study): rationale, design, and baseline characteristics. Mov Disord 2008;23:2194-2201

Notes to editors:

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Media contact:
Serena Thomson, Burson-Marsteller, London
Serena.thomson@bm.com
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