Date: 2012-06-01
Type of information: Results
phase: 3
Announcement: results
Company: Genzyme (USA - MA), a Sanofi company (France)
Product: Aubagio™ (teriflunomide)
Action
mechanism: Teriflunomide, a once-daily, oral tablet, is an immunomodulator with a unique mechanism of action. Although the mechanism of action for teriflunomide is not fully understood, research supports that teriflunomide inhibits the proliferation of stimulated T and B lymphocytes in the periphery thought to be responsible for the damaging inflammatory process in MS, while generally maintaining normal immune function.
Disease: relapsing multiple sclerosis
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country:
Trial
details: TOWER (Teriflunomide Oral in people With relapsing remitting multiplE scleRosis) is a Phase III, multi-center double-blind parallel-group placebo-controlled study of the efficacy and safety of teriflunomide in patients with relapsing MS followed by an open-label extension period. The TOWER study included patients ages 18 to 55. The primary endpoint was the annualized relapse rate, defined as the number of confirmed relapses per patient-year. The key secondary endpoint was time to disability progression confirmed for a minimum of 12-weeks. Safety variables were defined as adverse events reported by the patients or noted by the investigator during the study period.
Latest
news: Genzyme, a Sanofi company, has announced top-line results from the TOWER (Teriflunomide Oral in people With relapsing remitting multiplE scleRosis) trial that assessed the efficacy and safety of once-daily, oral teriflunomide in patients with relapsing forms of multiple sclerosis . In the study, patients receiving teriflunomide 14 mg had a statistically significant reduction in annualized relapse rate and risk of sustained accumulation of disability. Analysis of the full TOWER data is ongoing and results will be presented at a forthcoming scientific meeting. A 22.3 percent reduction in annualized relapse rate was observed in patients treated with teriflunomide 7 mg compared to placebo (p=0.02); there was no statistically significant difference observed between teriflunomide 7 mg and placebo for the risk of 12-week sustained accumulation of disability. Marketing applications for teriflunomide for the treatment of relapsing forms of MS are under review by the FDA, European Medicines Agency (EMA) and other regulatory authorities (See http://biopharmanalyses.fr/product/?pageid=274).
This double-blind, multi-center trial enrolled 1,169 patients and compared once-daily treatment with either 7 mg or 14 mg oral teriflunomide against placebo. Results from the primary and secondary endpoints for the proposed 14 mg commercial dose include the following:
• A 36.3 percent reduction in annualized relapse rate, the primary endpoint of the trial, was observed in patients who received teriflunomide compared to placebo (p<0.0001)
• A 31.5 percent reduction in the risk of 12-week sustained accumulation of disability, the main secondary endpoint, as measured by the Expanded Disability Status Scale (EDSS) was observed with teriflunomide compared to placebo (p=0.0442)
Patients who completed the trial were followed for a period between 48 and 173 weeks. The average duration of teriflunomide exposure in TOWER was 18 months. Adverse events observed in the trial were consistent with previous clinical trials with teriflunomide in MS. The most common types of adverse events reported more frequently in the teriflunomide arms were headache, ALT (Alanine transaminase) elevations, hair thinning, diarrhea, nausea and neutropenia. There was one death from a respiratory infection in the placebo arm and three deaths in the teriflunomide arms from a motor vehicle accident, suicide and sepsis.
