Tuesday, December 20, 2011

Genzyme sees setback with late-stage MS drug candidate

By Lori Valigra, Mass High Tech correspondent

Genzyme, a Sanofi company based in Cambridge, said its Phase 3 clinical trial of its oral teriflunomide drug for relapsing multiple sclerosis showed no statistical superiority when tested against an injectable interferon therapy called Rebif, an approved drug sold by Merck Serono.

The trial compared the effectiveness, safety, and tolerability of once-daily oral teriflunomide, also called Aubagio, to Rebif in 324 patients. The trial is the second completed study of five efficacy studies of teriflunomide in MS, making the clinical program one of the largest and broadest of any MS agent under development, the company said.

No statistical superiority was observed between Rebif and teriflunomide on the risk of treatment failure, the primary composite endpoint of the study. Risk of treatment failure was defined as the occurrence of a confirmed relapse or permanent treatment discontinuation for any cause, whichever came first. In the study, 48.6 percent of patients receiving 7 mg of oral teriflunomide and 37.8 percent of patients receiving 14 mg of oral teriflunomide reached the primary endpoint, versus 42.3 percent of patients receiving Rebif.

The company still expects to file an application for marketing authorization with the European Medicines Agency in the first quarter of 2012. The U.S. Food and Drug Administration (FDA) accepted the application for teriflunomide in October 2011.

The teriflunomide 14 mg daily dose and Rebif were not distinguishable on the endpoint of estimated annual relapse rate. The percentage of patients experiencing any adverse effects due to treatment was similar across all arms of the study.

Both the 7 mg and 14 mg doses of teriflunomide were safe and generally well tolerated. Most adverse events were mild, including nasopharyngitis, diarrhea, hair thinning, and back pain, but they occurred at a higher incidence than in Rebif, the company said. The most common adverse events observed in the Rebif arm were increases in alanine aminotransferase levels, headache and flu-like symptoms, which occurred more than in the teriflunomide arms. There were no deaths in the trial.

Genzyme plans to present detailed study findings at a forthcoming medical meeting. It also will include the results in its application with the European Medicines Agency for marketing authorization in the European Union, along with results from another successful Phase 3 trial.

In October 2011, the company said a separate Phase 3 study of teriflunomide, published in The New England Journal of Medicine, showed that drug candidate at the 14 mg dosage significantly reduced the annual relapse rate of MS, reduced disability progressions and improved several magnetic resonance imaging measures of disease activity, including new or worsening brain lesions.

In November 2011, Genzyme also reported positive Phase 3 trial results for its other MS drug candidate alemtuzumab, also known as Lemtrada. The Cambridge biotech said that Lemtrada met its two primary endpoints – reduced relapse rate and lower sustained accumulation of disability in MS patients taking Lemtrada compared to Rebif. Genzyme is working with Bayer Healthcare to develop Lemtrada, which was given fast track status for a quicker review process by the FDA.

Also in November, the company appointed Bill Sibold to head the MS business and oversee the development of the two potential MS treatments. He was recruited from Aliso Viejo, Calif.-based Avanir Pharmaceuticals (Nasdaq: AVNR), where he was the chief commercial officer. Sibold previously spent eight years at Biogen Idec (Nasdaq: BIIB), the maker of marketed multiple sclerosis therapies Avonex and Tysabri.