Tuesday, July 29, 2014

Strong efficacy of Alemtuzumab for multiple sclerosis treatment but had some serious adverse events

Alemtuzumab is an anti-CD52 humanized monoclonal antibody currently approved for the treatment of B-cell chronic lymphocytic leukemia.

Based on 5-years CAMMS223 trial, investigator said at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis that Alemtuzumab reduces disability and relapse rate over standard therapy with interferon beta-1a.

Marketed as Campath by Genzyme, a trial results showed strong efficacy for the treatment but still had serious adverse events compared with interferon beta, including immune thrombocytopenic purpura, thyroid disease and cancer.

The trial itself has been published in the New England Journal of Medicine as 3-year randomized and rater-blind study in 2008.

The phase 2 efficacy and safety trial used an active comparator over placebo and had 3 treatment arms – intravenous alemtuzumab, 12 or 24 mg, or subcutaneous interferon.

In that trial which involved 38 patients in the Alemtuzumab group went on to receier another disease-modifying therapy before the end of year 5 and 8 patients were re-treated with an additional cycle of alemtuzumab, instead investigators found the efficacy of alemtuzumab compared with patients receiving interferon to reduced the risk for sustained accumulation of disability (87% vs 62%), reduce mean disability while interferon increased disability, and reduced annualized rate of relapse (0.14 vs 0.28).

However, there were 6 cases of immune thrombocytopenic purpura by alemtuzumab, 1 patient died, 64 thyroid events (4 were serious), graves opthalmopathy, and 1 patient required surgical decompression.

While there were developed of colon cancer treated by interferon, malignant tumors with alemtuzumab included breast and cervical cancer, Burkitt’s lymphoma, thyroid papillary carcinoma, and basal cell carcinoma.

The most common adverse events were infusion-associated reactions. The most frequent infections were upper respiratory tract, urinary tract, and oral herpes.

Although an accompanying editorial, Stephen Hauser, MD, from the University of California at San Francisco, noted that the study “highlight the value of very aggressive therapy instituted at the beginning of the disease process, a time when the majority of inflammatory damage is subclinical and disability is absent or mild in most patients”, however, many physicians at the meeting said that they wouldn’t consider alemtuzumab for multiple sclerosis.

As many physicians dislike with efficacy compared to the risks, a medical director at the Providence Multiple Sclerosis Center in Portland, Oregon, Stanley Cohan, MD, said, “I don’t think this drug will be approved, but if it were available, I wouldn’t use it.”

According to Dr. Cohan, even the efficacy are powerful, but the safety issues are problematic.

The authors of the study, Alasdair Coles, PhD, from Cambridge University in the United Kingdom acknowledged that many of his colleagues do not agree with the idea of using alemtuzumab in multiple sclerosis. But, there is a cost to handle increasing disability with interferon compared to alemtuzumab that reduced mean disability.

The study itself funded by Genzyme Corporation, and phase 3 trials are currently underway to evaluate alemtuzumab in treament-naive patients similar to those described in the current study.

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