Date: 2012-11-14
Type of information: Results
phase: 3
Announcement: results
Company: Genzyme (USA - MA), a Sanofi company (France)
Product: Lemtrada® (alemtuzumab)
Action
mechanism: This humanized monoclonal antibody targets the cell-surface glycoprotein CD52, which is often expressed on T- and B-lymphocytes. Preliminary research suggests that alemtuzumab depletes the T- and B-cells that may be responsible for the cellular damage in multiple sclerosis, while potentially sparing other cells of the immune system. Early alemtuzumab research has also suggested a distinctive pattern of lymphocyte reconstitution in patients following treatment.
Disease: multiple sclerosis
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country:
Trial
details: CARE-MS II (The Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis) is a randomized Phase III clinical trial comparing the investigational drug alemtuzumab to interferon beta-1a (Rebif® - 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.
Latest
news: * On November 14, 2011, Genzyme has reported 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 co-primary endpoints were highly statistically significant. 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. 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 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 life-threatening or fatal infections. Approximately 16 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related 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. Genzyme expects to submit Lemtrada® for review to US and EU regulatory authorities in the first quarter of 2012.
