Positive top-line results from alemtuzumab Phase 3 trial on multiple sclerosis

Sanofi (EURONEXT: SAN and NYSE: SNY) and its subsidiary Genzyme announced today positive top-line results from CARE-MS I, the first of two randomized, Phase 3 clinical trials comparing the investigational drug alemtuzumab to the approved multiple sclerosis therapy Rebif^® (high dose subcutaneous interferon beta-1a) in patients with relapsing-remitting multiple sclerosis (RRMS). Genzyme is developing alemtuzumab in MS in collaboration with Bayer HealthCare.

In the CARE-MS I trial, 2 annual cycles of alemtuzumab treatment resulted in a 55 percent reduction in relapse rate compared to Rebif^® over the two years of the study (p<0.0001), hence satisfying the first primary endpoint, and therefore meeting the predefined protocol criteria for declaring the study a success. Statistical significance was not achieved for the second primary endpoint, time to six month sustained accumulation of disability, as compared to Rebif®. At the two year time point, 8 percent of alemtuzumab treated patients had a sustained increase in their Expanded Disability Status Scale (EDSS) score (or worsening) as compared to 11 percent of those who received Rebif® (Hazard)

"The substantial effect of alemtuzumab on reduction of relapse rate over and above that seen with Rebif^® confirms our experience gathered over many years and demonstrated in the Phase 2 study," said Professor Alastair Compston, Chair of the Steering Committee overseeing the conduct of the study, and head of the Department of Clinical Neurosciences at the University of Cambridge, United Kingdom. "We treated patients in CARE-MS I at a very early stage in the course of their illness when the natural history may be relatively quiet, and both groups were remarkably stable over the two years of observation. Very few patients accumulated disability at the rate expected from previous clinical trials, including our Phase 2 experience. Whilst welcome from the clinical perspective, this much reduced our ability to detect a significant treatment effect on the disability endpoint."

"In this 2-year comparative study, the effect of alemtuzumab on reducing relapses versus Rebif, a leading drug for the treatment of Multiple Sclerosis, is impressive, and the safety profile is consistent with the Phase 2 clinical trial experience," said Christopher A. Viehbacher, Chief Executive Officer, Sanofi. "We look forward to the results from CARE-MS II, which will provide clinical data in patients whose disease was not adequately controlled on other multiple sclerosis therapies. Today's results are an important step forward in the development of alemtuzumab to address the substantial unmet needs for multiple sclerosis patients."

The most common adverse events associated with alemtuzumab in the CARE-MS I study included infusion-associated reactions, the symptoms of which most commonly included headache, rash, fever, nausea, flushing, hives and chills. The incidence of infections was also increased, the most common infections involving the upper respiratory and urinary tract and oral herpes. Infections were predominantly mild to moderate in severity and there were no life-threatening or fatal infections.

No alemtuzumab patient discontinued from the study due to an adverse event. Less than 20 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event and less than 1 percent developed immune thrombocytopenia during the 2 year study period. There were no cases of anti-GBM disease. Cases of autoimmunity were detected and managed using conventional therapies. Patient monitoring for immune cytopenias and thyroid or renal disorders is incorporated in all Genzyme-sponsored trials of alemtuzumab for the investigational treatment of MS. Analysis of the full CARE-MS I data is ongoing.

CARE-MS I, which enrolled 581 early, active RRMS patients who had received no prior MS therapy, was a global, randomized, rater-blinded clinical trial to determine the efficacy and safety of alemtuzumab in this population. The company anticipates presenting detailed CARE-MS I study findings at a medical meeting later this year.

Another Phase 3 clinical trial, CARE-MS II, is currently underway, evaluating alemtuzumab against Rebif® in relapsing-remitting multiple sclerosis patients who have relapsed while on therapy. Top-line results from that trial are expected to be available in the fourth quarter of 2011. Since it is not yet approved for the treatment of MS, alemtuzumab must not be used in MS patients outside of a formal, regulated clinical trial setting in which appropriate patient monitoring measures are in place.