Teva Pharmaceutical Industries Ltd. and Active Biotech AB announced that patients are being enrolled for the BRAVO phase III pivotal trial.

BRAVO is a global, 24-month, double-blind study designed to evaluate the efficacy, safety and tolerability of the oral compound laquinimod versus placebo, and to provide risk-benefit data for laquinimod versus a currently available injectable treatment, Avonex. The BRAVO trial, which was initiated in April this year, aims to enrol approximately 1,200 patients with relapsing-remitting multiple sclerosis (RRMS). A second global phase III trial of laquinimod including 1,000 patients, ALLEGRO, is also ongoing and recruiting patients globally.

"All currently approved multiple sclerosis (MS) treatments are administered via injection or infusion. The ability to provide a safe and effective oral treatment option would be a significant advancement for the treatment of MS," said Dr. Timothy Vollmer, Medical Director, Rocky Mountain MS Center, Denver, Colorado, and principal investigator of the BRAVO study. "Additionally, the mode of action for laquinimod is unlike any other MS compound, existing or experimental. We are hopeful that this research will expand our abilities to combat the disease through novel targeting."

Data recently published in The Lancet* demonstrated that oral dose of laquinimod significantly reduced the median magnetic resonance imaging (MRI) disease activity by 60 percent, compared to placebo and was well tolerated in RRMS patients. The majority of patients from the study are still receiving treatment with laquinimod in an open-label extension trial.

The safety profiles of oral therapies are of increasing interest to the MS community; We are hopeful that laquinimod will be both efficacious and safe thus providing patients with an optimal risk-benefit profile," said Dr. Per Soelberg Sorensen, Danish Multiple Sclerosis Research Center, Department of Neurology, Copenhagen University Hospital, and principal investigator of the BRAVO study.

BRAVO (benefit-risk assessment of Avonex and laquinimod) is a pivotal, multinational, multi-center, randomized, double-blind, parallel-group, placebo-controlled study designed to compare the safety and efficacy of laquinimod with placebo and to provide risk-benefit data for laquinimod versus a currently available injectable treatment, Avonex. The enrolment goal is approximately 1,200 patients with RRMS. The globally conducted study will include centres in the United States, Europe, and Israel.

ALLEGRO is a pivotal, global, 24/30-month, double-blind, Phase III study designed to evaluate the efficacy, safety and tolerability of laquinimod versus placebo in the treatment of relapsing-remitting multiple sclerosis (RRMS). The Allegro trial aims to enrol approximately 1,000 patients with RRMS. The globally conducted study will include centres in the United States as well as centers throughout Canada, Europe, and Israel.

Laquinimod is a novel once-daily, orally administered immunomodulatory compound that is being developed as a disease-modifying treatment for RRMS. Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries, Ltd. in June 2004. A phase IIb study in 306 patients was recently published in The Lancet and demonstrated that an oral 0.6 mg dose of laquinimod, administered daily, significantly reduced MRI disease activity by a median of 60 percent versus placebo in RRMS patients. Laquinimod also showed consistent and robust effect on all secondary MRI endpoints. In addition, the study showed a favourable trend toward reducing annual relapse rates and the number of relapse-free patients compared with placebo. Treatment was well tolerated, with only some transient and dose-dependent increases in liver enzymes reported. Over 460 MS patients have received laquinimod in various phase I-II clinical trials.