A new study comparing the investigational oral teriflunomide (Sanofi-Aventis) with Rebif® (interferon beta-1a, EMD Serono and Pfizer) in relapsing multiple sclerosis did not reach its primary endpoint, announced Sanofi-Aventis and its subsidiary Genzyme in a press release dated December 20, 2011. The primary endpoint (the main question posed by the study) was “risk of failure,” meaning the first occurrence of a relapse, or permanent discontinuation of the study treatment, whichever came first. There was no significant difference in the numbers of participants who experienced events defined as treatment failure among the teriflunomide and Rebif groups.
According to the press release, detailed results of the TENERE study will be presented at an upcoming medical meeting. This is the second completed of five phase III studies involving teriflunomide in multiple sclerosis. An application for marketing approval of teriflunomide was accepted for review by the U.S. Food and Drug Administration in October 2011.
Background: Multiple sclerosis occurs when the immune system attacks the brain and spinal cord. Teriflunomide is a novel oral compound that inhibits the function of specific immune cells. In the TEMSO study reported earlier this year, teriflunomide reduced the average number of MS relapses and disease activity on MRI scans significantly more than inactive placebo in 796 people with relapsing forms of MS. Read more about this study.
Other phase 3 studies of teriflunomide are ongoing, including the TOWER study in 1110 people with relapsing forms of MS (teriflunomide vs. placebo); the TOPIC study in 780 people at high risk for developing MS (teriflunomide vs. placebo); and the TERACLES study in 1455 people with relapsing MS (teriflunomide vs. placebo added on to interferon beta).
The Study: For the TENERE trial, investigators worldwide recruited 324 people with relapsing MS, and randomly assigned them to receive teriflunomide 7 mg or 14 mg, once daily by mouth, or Rebif 44 mcg three times per week subcutaneously for 48 weeks. The primary endpoint was “risk of failure,” meaning the first occurrence of a relapse, or permanent discontinuation of the study treatment, whichever came first. Secondary outcome measures included the average number of relapses per year, fatigue as reported by participants in the Fatigue Impact Scale, and satisfaction as reported by participants using the Treatment Satisfaction Questionnaire for Medication. Safety and tolerability were also assessed.
There was no significant difference in the numbers of participants who experienced events that constituted the definition of treatment failure among the teriflunomide and Rebif groups, according to the press release. Relapse rates did not differ significantly either. Details on other secondary endpoints were not provided.
Both treatments were safe and generally well tolerated. Participants in the teriflunomide groups experienced more nasal inflammation, diarrhea, hair thinning, and back pain. Those in the Rebif group experienced more increases in liver enzyme levels, headache, and flu-like symptoms.
Comment: These and results from additional phase III studies of teriflunomide that have been completed or are now underway should help define the short-term safety and promise of teriflunomide as a potential new therapy for relapsing MS.
Rebif is a registered trademark of EMD Serono and Pfizer.