Genzyme announces successful Phase III results for Alemtuzumab (LEMTRADA) in multiple sclerosis

Sanofi (EURONEXT: SAN and NYSE: SNY) and its subsidiary Genzyme report today that the Phase lll CARE-MS ll trial met both of its co-primary endpoints. Relapse rate and sustained accumulation (worsening) of disability (SAD) were significantly reduced in multiple sclerosis patients receiving alemtuzumab (LEMTRADA™) as compared with Rebif® (44 mcg subcutaneous interferon beta-1a). Results for both of these coprimary endpoints were highly statistically significant. CARE-MS II is the randomized Phase III clinical trial comparing the investigational drug alemtuzumab to interferon beta-1a in patients with relapsing-remitting multiple sclerosis (RRMS). Patients were required to have experienced a relapse while on a prior therapy to be eligible for CARE-MS II. Genzyme is developing alemtuzumab in MS in collaboration with Bayer HealthCare.

In this randomized trial involving 840 patients, a 49 percent reduction in relapse rate was observed in patients treated with alemtuzumab 12 mg compared to interferon beta-1a over two years of study (p<0.0001). Importantly, there was also a 42 percent reduction in the risk of sustained accumulation (worsening) of disability as measured by the Expanded Disability Status Scale (EDSS) (p=0.0084). Analysis of the full CARE-MS II data is ongoing and results will be presented at a forthcoming scientific meeting.

“CARE-MS ll represents the culmination of many years of clinical and laboratory research aimed at demonstrating the potential for alemtuzumab as a highly effective treatment for MS and understanding mechanisms involved in the complex natural history of the disease,” 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. “Taken together, the Phase ll and lll clinical trial data illustrate the promise that alemtuzumab holds as a transformative treatment for people with relapsing MS.”

The CARE-MS II trial compared treatment with alemtuzumab 12 mg given daily as an IV administration for 5 days, and then again for 3 days one year later, to treatment with interferon beta- 1a 44 mcg administered by injection three times per week throughout the two years of study.

“The superior efficacy results for alemtuzumab, particularly the slowing of disability, are very promising since this was a head-to-head comparison trial with high dose subcutaneous interferon beta-1a,” said Dr. Jeffrey Cohen, Professor of Medicine (Neurology), Cleveland Clinic Lerner College of Medicine; Director of Experimental Therapeutics, Mellen Center for MS Treatment and Research; and a member of the Steering Committee overseeing the conduct of the study. “These results suggest alemtuzumab’s potential to offer patients with MS a new and effective treatment option.”

The safety profile observed in the trial was consistent with previous alemtuzumab use in MS and adverse events continued to be manageable. The most common types of adverse events associated with alemtuzumab in the CARE-MS II study were infusion-associated reactions, the symptoms of which most commonly included headache, rash, nausea, hives, fever, itching, insomnia, and fatigue. Infections were common in both groups with a higher incidence in the alemtuzumab group. The most common infections in patients receiving alemtuzumab included upper respiratory and urinary tract infections, sinusitis and herpes simplex infections. Infections were predominantly mild to moderate in severity and there were no treatment-related lifethreatening or fatal infections.

Approximately 16 percent of alemtuzumab-treated patients developed an autoimmune thyroidrelated adverse event and approximately one percent developed immune thrombocytopenia during the two-year study period. These cases were detected early through a monitoring program 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.

“We are very pleased with the results of the CARE-MS II study which are unprecedented,” said David Meeker, M.D., President and Chief Executive Officer, Genzyme. “We believe that LEMTRADA™, with its impressive efficacy, novel dosing regimen and manageable safety profile, could make a very important contribution to the MS treatment landscape, where a significant unmet need still exists for many patients. Based on these positive results, we are on track to submit LEMTRADA™ for review to US and EU regulatory authorities in the first quarter of 2012.”

Alemtuzumab has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA). The FDA’s Fast Track program is designed to expedite the review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs. Under Fast Track designation, alemtuzumab for MS is eligible for Priority Review. 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.

*LEMTRADA™ is the proprietary name submitted to health authorities for the company’s investigational multiple sclerosis agent alemtuzumab.

About the CARE-MS II Trial

CARE-MS II (The Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis) trial was designed to evaluate whether the investigational MS therapy alemtuzumab could achieve meaningful efficacy and safety improvements over the approved, active comparator interferon beta- 1a, a standard treatment for relapsing MS.

CARE-MS II was a Phase III, global, randomized clinical trial comparing treatment with alemtuzumab to treatment with subcutaneous interferon beta-1a (44 mcg administered by injection three times per week) in 840 patients who relapsed despite receiving prior MS treatment. Patients enrolled in the trial had to have experienced at least two relapses within the two years prior to entering the trial, with at least one of these relapses occurring within one year prior to enrollment and at least one relapse occurring while on MS therapy.

The CARE-MS II trial had two co-primary endpoints: reduction in relapse rate and six months sustained accumulation of disability (SAD)**. Secondary outcome measures include: Percentage of relapse-free patients at year two; Expanded Disability Status Scale (EDSS) change from baseline; percent change in magnetic/resonance imaging (MRI)-T2-hyperintense lesion volume at year two; and Multiple Sclerosis Functional Composite (MSFC) change from baseline. Disability assessments were performed at regularly scheduled visits by independent, evaluating neurologists who were blinded to the patients’ treatment assignments. Relapse was determined by a blinded committee.

**Sustained Accumulation of Disability – Clinical representation of the worsening of a patient’s level of disability; CARE-MS ll monitored this endpoint over the course of six months.

About Alemtuzumab

Alemtuzumab is a humanized monoclonal antibody being studied as a potential therapy for relapsing MS. Alemtuzumab targets the cell-surface glycoprotein CD52, which is highly expressed on T- and B-lymphocytes. Preliminary research suggests that alemtuzumab initially depletes the Tand B-cells that may be responsible for the cellular damage in MS. This depletion of T- and B-cells is followed by a distinctive pattern of lymphocyte repopulation. Alemtuzumab appears to have little or no effect on other cells of the immune system. In addition to the completed CARE-MS II study, another Phase III trial, CARE-MS I, evaluated alemtuzumab against interferon beta-1a in relapsingremitting MS patients naive to prior treatment and found a statistically significant reduction in relapse rate with alemtuzumab.

Genzyme has the worldwide rights to alemtuzumab and has primary responsibility for the development and commercialization of alemtuzumab in MS. Bayer HealthCare has been codeveloping alemtuzumab in MS with Genzyme. Bayer HealthCare retains an option to co-promote alemtuzumab in MS and upon regulatory approval and commercialization would receive contingent payments based on sales revenue.