Sanofi and its subsidiary Genzyme have announced results from CARE-MS I, the first of two randomized, Phase 3 clinical trials comparing the investigational drug Alemtuzumab ( Lemtrada ) to the approved multiple sclerosis therapy Rebif ( high dose subcutaneous Interferon beta-1a ) in patients with relapsing-remitting multiple sclerosis ( RRMS ).

In the CARE-MS I trial, 2 annual cycles of Alemtuzumab treatment resulted in a 55% 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% of Alemtuzumab treated patients had a sustained increase in their Expanded Disability Status Scale ( EDSS ) score as compared to 11% of those who received Rebif ( hazard ratio, HR=0.70, p=0.22 ). The patients will have the option to be evaluated over the next 3 years as part of a separate protocol.

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.

CARE-MS I ( Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis, Study One ), has compared two annual cycles of intravenous Alemtuzumab, 12 mg/day for 5 days initially and for 3 days a year later, to three-times weekly subcutaneous Interferon beta-1a ( Rebif ) in treatment-naïve patients with relapsing-remitting multiple sclerosis.
The study enrolled 581 patients who had not previously received treatment to suppress multiple sclerosis, except steroids.
The study’s primary outcome measures were reduction in relapse rate and time to sustained accumulation of disability. Secondary outcome measures include: proportion of patients who are relapse-free at year two; change from baseline in EDSS; acquisition of disability as measured by change from baseline in Multiple Sclerosis Functional Composite ( MSFC ); and percent change from baseline in MRI-T2 hyperintense lesion volume at year two.
Additional endpoints included the safety and tolerability of Alemtuzumab.

Alemtuzumab, a humanized monoclonal antibody, targets the cell-surface glycoprotein CD52, which is highly 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 repopulation following Alemtuzumab treatment.

Source: Sanofi, 2011

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