European Approval for Teriflunomide in MS

Susan Jeffrey

August 31, 2013

Genzyme, a Sanofi company, announced today that the European Commission has granted marketing authorization for teriflunomide (Aubagio), 14 mg, for the treatment of adult patients with relapsing-remitting multiple sclerosis (MS).

Teriflunomide is a once-daily oral agent that is already approved in the United States, where the 7-mg dose is also approved, as well as in Australia, Argentina, Chile, and South Korea, for this indication. It is under review in several other countries.

The company received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in March this year, reported by Medscape Medical News at that time.

Teriflunomide is an immunomodulator with anti-inflammatory properties. Approval is based on results of a program of phase 3 trials. Results of the TEriflunomide Multiple Sclerosis (TEMSO) trial, published in the New England Journal of Medicine in 2011, showed a significant reduction in annualized relapse rate and sustained accumulation of disability with both the 7- and the 14-mg daily doses vs placebo.

A second phase 3 trial, TENERE, showed the agent was similar to interferon β-1a (Rebif, Merck Serono), a standard approved treatment for MS.

A third trial, Teriflunomide Oral in people With relapsing-remitting multiplE scleRosis (TOWER), showed a significant reduction in annualized relapse rates and sustained accumulation of disability with the 14-mg dose vs placebo. A second dose studied in this trial, 7 mg, showed a reduction in relapse rate but not in sustained accumulation of disability.

"The fact that Aubagio 14 mg has demonstrated a positive effect on disability progression in 2 phase 3 clinical studies underscores its importance as a new treatment option for relapsing-remitting MS patients," said Professor Ludwig Kappos, MD, chair of neurology, University Hospital, Basel, Switzerland, in a release from Genzyme/Sanofi. "As a new once-daily, oral treatment option with well-characterized safety and tolerability, Aubagio could be an attractive option for patients dissatisfied with traditional injectable therapies."

As in the United States, where these risks are noted in a black box warning, the teriflunomide label mentions the risk for hepatotoxicity and teratogenicity based on animal data.

In clinical studies, the incidence of serious adverse events were similar among teriflunomide- and placebo-treated patients; the most common adverse events associated with treatment included increased alanine aminotransferase levels, alopecia, diarrhea, influenza, nausea, and paresthesia. Teriflunomide is the principal active metabolite of leflunomide, which is indicated in the United States and Europe for the treatment of rheumatoid arthritis. Severe liver injury, including fatal liver failure, has been reported in patients treated with leflunomide, the company release notes.

Teriflunomide is contraindicated in patients with severe hepatic impairment; pregnant women; women of childbearing potential who are not using reliable contraception; breast-feeding women; patients with immunodeficiency states; patients with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia, or thrombocytopenia; patients with severe active infection until resolution; patients with severe renal impairment undergoing dialysis; and patients with hypoproteinemia.

Full prescribing information and more information about teriflunomide in the European Union can be found here. Full prescribing information and more information about teriflunomide in the United States can be found here.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: