Date: 2012-10-12
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of data at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)
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 forms of multiple sclerosis
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country:
Trial
details: TOWER is a Phase III, multi-center double-blind parallel-group placebo-controlled study of the efficacy and safety of Aubagio® 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: Sanofi and its subsidiary Genzyme have announced that key data from the TOWER trial were presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). In the study, once-daily, oral Aubagio® 14 mg significantly reduced the annualized relapse rate and slowed progression of disability in patients with relapsing forms of multiple sclerosis (MS) compared to placebo. In addition, the proportion of patients treated with Aubagio® who were relapse-free was significantly higher compared to placebo.
TOWER (Teriflunomide Oral in people With relapsing multiplE scleRosis) is a randomized, double-blind Phase III trial that enrolled 1,169 patients with relapsing MS across 26 countries and compared 7 mg or 14 mg once-daily, oral Aubagio® against placebo. The company announced positive top-line results in June. In September, the FDA approved Aubagio® as a once-daily oral treatment for patients with relapsing forms of MS.
TOWER data presented for the first time for the 14 mg dose include:
• A 36.3 percent reduction in annualized relapse rate (ARR= 0.319), the primary endpoint of the trial, as compared to placebo (ARR=0.501) (p=0.0001); Fifty-two percent of patients treated with this dose were also relapse-free, meaning they did not experience any relapses during the study, compared to 38 percent with placebo (37 percent risk reduction; 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), compared to placebo [p=0.0442].
In addition, a 22.3 percent reduction in annualized relapse rate (ARR= 0.389) was observed in patients treated with Aubagio® 7 mg compared to placebo (p=0.02); Further, 55 percent of patients treated with 7 mg Aubagio® were relapse-free, as compared with 38 percent on placebo (p=0.0016). There was no statistically significant difference observed between Aubagio® 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 Aubagio® exposure in TOWER was 18 months.
Adverse events observed in the trial were consistent with those seen in previous studies of Aubagio® in MS. The proportion of patients with treatment-emergent adverse events was similar across all treatment arms. The most common adverse events reported more frequently in the Aubagio® arms were headache, ALT (Alanine aminotransferase) elevations, hair thinning, diarrhea, nausea and neutropenia. As previously reported, 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.
