During the 30th Congress of the European Committee for Research and Treatment in Multiple Sclerosis (ECTRIMS) last week in Boston, Teva Pharmaceutical Industries Ltd. (NYSE:TEVA), together with Active Biotech (NASDAQ OMX NORDIC:ACTI), presented new follow-up data evaluating the clinical safety of laquinimod in patients with relapsing-remitting multiple sclerosis (RRMS) who were treated with laquinimod in Phase II, Phase III, and open-label extension studies for two or more years.
Teva Pharmaceutical Industries Ltd. (NYSE:TEVA), based in Israel, is the worldwide leading generic drug manufacturer, with a clinical focus on central nervous system (CNS) conditions, including pain, respiratory, oncology, and women’s health therapeutic areas as well as biologics. Active Biotech AB (NASDAQ OMX NORDIC:ACTI), located in Sweden, is a biotechnology company with focus on autoimmune/inflammatory diseases and cancer. Active is currently testing the laquinimod therapy, which is given orally, has immunomodulatory properties, and is used for the treatment of multiple sclerosis (MS).
“These data may be important as they further support the clinical safety profile of laquinimod,” said Michael Hayden, M.D., Ph.D., President of Global R&D and Chief Scientific Officer at Teva Pharmaceutical Industries, Ltd. “We believe laquinimod may have the potential to help physicians address certain gaps within the MS treatment paradigm as a potential therapeutic option when considering the benefits and risks in a longer-term setting.” added Michael Hayden.
The global Phase III clinical development program for the evaluation of laquinimod in MS includes 3 trial studies, ALLEGRO and BRAVO, which are testing one oral dose, 0.6 mg, and a third, named CONCERTO, which is evaluating two doses of the compound, 0.6mg and 1.2mg, per day. In the ALLEGRO and BRAVO trials, adverse reactions (AE) included headache, abdominal pain, back and neck pain, appendicitis, and mild, asymptomatic laboratory abnormalities, including liver enzyme elevations, like alanine aminotransferase (ALT), hematological changes, and elevation of C-reactive protein (CRP) or fibrinogen levels. The CONCERTO trial enrolled 2,100 patients with duration of 24 months. The primary outcome of this trial will be the measurement of disability progression of the patients using the Kurtzke Expanded Disability Status Scale (EDSS).
In the pooled safety analysis, rates of adverse and serious events were lower in the open-label extensions when compared with the core studies. Moreover, during these extensions, less than three percent of patients stopped the treatment due to AEs. Additionally, patients exposed to at least two years of laquinimod had lower changes in ALT experimental values (1.18% reached >3x upper limit of normal (ULN) ALT vs. 4.72% for laquinimod and 2.6% for placebo [inactive compound]) during the core study. In the double-blind phase and open-label extensions of the Phase II LAQ/5063 and the Phase III ALLEGRO and BRAVO trials, the safety analysis included patients exposed to laquinimod, 0.6 mg per day, for two or more years (n=1009), with a mean exposure of 3.7 (±1.0) years.
“In this pooled analysis, laquinimod has shown to be safe for patients taking the treatment for two or more years, which supports the safety profile of laquinimod when used in a longer-term setting,” said Professor Giancarlo Comi, Director of the Department of Neurology and Institute of Experimental Neurology at the San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Italy. “In a separate analysis, we were pleased to see that when used in a longer-term setting, laquinimod continued to show a favorable effect on relapses and confirmed disability progression, maintaining the benefits previously seen in Phase III studies.” added Professor Giancarlo Comi.
In addition to the MS clinical studies, laquinimod will be assessed in terms of efficacy, safety, and tolerability for other neurodegenerative diseases including Huntington’s disease.