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 ( Aubagio ) in patients with relapsing forms of multiple sclerosis ( MS ) were presented.
In the study, patients receiving Teriflunomide 14 mg had a statistically significant reduction in annualized relapse rate and risk of sustained accumulation of disability.
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) a 36.3% reduction in annualized relapse rate, the primary endpoint of the trial, was observed in patients who received Teriflunomide compared to placebo ( p less than 0.0001 );
b) a 31.5% 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 )
c) a 22.3% 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.
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 multiple sclerosis.
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.
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 multiple sclerosis, while generally maintaining normal immune function.
TOWER is a phase III, multi-center double-blind parallel-group placebo-controlled study of the efficacy and safety of Teriflunomide in patients with relapsing multiple sclerosis 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. ( Xagena )
Source: Genzyme, 2012