Teva Pharmaceutical Industries Ltd. and Active Biotech announced initial results from the phase III BRAVO study, which was designed to evaluate the efficacy, safety and tolerability of oral laquinimod compared to placebo and to provide a benefit-risk assessment comparing oral laquinimod and a reference arm of injectable Interferon beta-1a (Avonex). BRAVO is the second of two pivotal phase III studies in the clinical development programme for laquinimod, an investigational, oral, once-daily therapy for the treatment of relapsing-remitting multiple sclerosis (RRMS). Results showed that the BRAVO study did not achieve its primary endpoint of reducing the annualized relapse rate (p=0.075).

The randomization process for BRAVO was adequately performed; however, placebo and treatment study groups showed dissimilarity in two baseline magnetic resonance imaging (MRI) characteristics. According to a standard and pre-specified sensitivity analysis included within the original statistical analysis plan, when this imbalance was corrected laquinimod demonstrated a significant reduction in the annualized relapse rate (21.3%, p=0.026), in the risk of disability progression as measured by Expanded Disability Status Scale (EDSS) (33.5%, p=0.044) and in brain volume loss (27.5%, p<0.0001).

The BRAVO findings support the direct effect of laquinimod within the central nervous system (CNS) and are in line with the results of the first laquinimod phase III trial, ALLEGRO. Additionally, as in ALLEGRO, the BRAVO study found that laquinimod demonstrated a favourable safety and tolerability profile compared to placebo.

Compared to placebo, treatment with Interferon beta-1a reduced annualized relapse rates; however, a reduction in brain tissue loss was not demonstrated and a reduction in the progression of disability did not yield a supportive p value.

The BRAVO study was not designed to provide direct statistical comparisons of efficacy endpoints between the two active arms.

"We are encouraged by the overall outcomes achieved in the laquinimod phase III clinical development program, and plan to submit applications to regulatory authorities in the US and EU," said Professor Yitzhak Peterburg, Teva's Group vice president, Global Branded Products. "Teva remains committed to the clinical development of laquinimod and is confident that the drug could provide a unique option for the treatment of multiple sclerosis."

"Data from the ALLEGRO and BRAVO studies demonstrated that laquinimod reduced disability and brain tissue loss, two of the most important goals in the treatment of relapsing forms of multiple sclerosis," said Professor Per Soelberg rensen, MD, Head of MS Research Unit, Copenhagen University Hospital, Rigshospitalet, Co-principal investigator of the BRAVO study. "These effects, coupled with a favorable safety profile and a once-daily dosing regimen create a promising potential treatment for the disease."

Additional analyses of the BRAVO study data are ongoing, and results will be submitted for presentation at a scientific congress later in the year.

BRAVO was a two-year, multi-national, multi-center, randomized, double-blind, parallel-group, placebo-controlled study designed to compare the safety, efficacy and tolerability of a once-daily oral dose of 0.6 mg laquinimod over placebo and to provide a descriptive comparison of the risk-benefit profiles of laquinimod and interferon beta-1a. The primary outcome measure was to assess the efficacy of 0.6 mg daily dose of laquinimod as measured by the relapse rate. Secondary outcome measures included impact on the accumulation of disability and brain atrophy. The BRAVO study completed enrollment in June 2009, recruiting more 1,331 patients at 153 sites worldwide, including in the US, Europe, Russia, Israel and South Africa.

Laquinimod is an oral, once-daily immunomodulator with a novel mechanism of action being developed for the treatment of MS. The global phase III clinical development program evaluating oral laquinimod in MS consists of two pivotal studies, ALLEGRO and BRAVO. In the ALLEGRO study, laquinimod demonstrated a significant positive impact on disease activity, disability progression and MRI measures of inflammation and neurodegeneration, while maintaining a favourable safety and tolerability profile. Specifically, laquinimod showed a statistically significant 23 per cent reduction in annualized relapse rate and 36 per cent significant reduction in the risk of confirmed disability progression, as measured by EDSS.

In addition to the MS clinical studies, laquinimod is currently in phase II development for Crohn's disease and Lupus, and is being studied in other autoimmune diseases.

Teva Pharmaceutical Industries Ltd. is a leading global pharmaceutical company, committed to increasing access to high-quality healthcare by developing, producing and marketing affordable generic drugs as well as innovative and specialty pharmaceuticals and active pharmaceutical ingredients.

Active Biotech AB is a biotechnology company with focus on autoimmune/inflammatory diseases and cancer. Projects in or entering pivotal phase are laquinimod, an orally administered small molecule with unique immunomodulatory properties for the treatment of multiple sclerosis, TASQ for prostate cancer as well as ANYARA for use in cancer targeted therapy, primarily of renal cell cancer.