Teva Pharmaceutical Industries Ltd. and Active Biotech announced initial results from the two-year phase III ALLEGRO study, which demonstrated that relapsing-remitting multiple sclerosis (MS) patients treated with 0.6 mg daily oral laquinimod experienced a statistically significant reduction in annualized relapse rate compared to placebo. Additional clinical endpoints, including significant reduction in disability progression, as measured by Expanded Disability Severity Scale (EDSS), were also achieved.
Laquinimod was safe and well-tolerated. The overall frequencies of adverse events were comparable to those observed in the placebo group. No deaths were reported in laquinimod-treated patients. Overall incidence of infections was similar between the two arms of the trial.
"This pivotal study met its primary endpoint while maintaining a very good safety profile," says Principal Investigator, Professor Giancarlo Comi, director of the Department of Neurology and Institute of Experimental Neurology at the University Vite Salute, San Raffaele, Italy. "Laquinimod demonstrated a significant reduction in the progression of disability which may be explained by its unique mechanism of action that includes neuroprotective properties. Laquinimod may therefore be a promising therapeutic option for the MS community."
"We are very pleased to have achieved this major milestone in the development of oral laquinimod, a novel therapy that can potentially improve the lives of many MS patients in a safe way," said Shlomo Yanai, Teva's president and chief executive officer.
Additional analyses of the ALLEGRO study data are ongoing, and detailed results will be submitted for presentation at a leading scientific conference during the first half of 2011.
Laquinimod received Fast Track designation from the U.S. Food and Drug Administration (FDA) in February 2009. The second phase III study, BRAVO is still ongoing with results anticipated in the third quarter of 2011. Regulatory submissions in the US and the EU will then follow.
In addition to the ongoing MS clinical studies, laquinimod is currently in Phase II development for Crohn's disease and Lupus, and is being studied in other autoimmune diseases.
Following the successful study results, Teva filed a patent application covering the use of laquinimod in slowing the progression of disability in MS patients.
Laquinimod is a novel once-daily, oral immunomodulatory compound being developed as a disease-modifying treatment for MS. The global Phase III clinical development program evaluating oral laquinimod in MS consists of two pivotal studies, ALLEGRO and BRAVO:
The first clinical study, ALLEGRO, was a two-year multi-national, multi-center randomized, double blind, placebo-controlled study designed to evaluate the efficacy, safety and tolerability of laquinimod in MS patients. The study was conducted at 139 sites in 24 countries and enrolled 1,106 MS patients. Patients were randomized to receive a once-daily oral dose of 0.6 mg laquinimod or matching placebo. The primary outcome measure was the number of confirmed relapses; secondary measures included confirmed disability progression and changes in MRI active lesions. Patients who completed the ALLEGRO study are offered to join an open-label extension phase, in which they will be treated with laquinimod 0.6mg daily until the drug is commercially available.
The second clinical study, BRAVO, is 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 perform a comparative risk-benefit assessment between laquinimod and interferon beta-1a. Enrollment of 1,332 patients at 154 sites in the U.S, Europe, Israel and South Africa was completed in June 2009. BRAVO study results are expected in the third quarter of 2011.
In addition to the ongoing 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.