Genzyme Reattempts Relapsing-remitting Multiple Sclerosis Indication for Alemtuzumab

Internal Medicine World ReportJune 2014

European regulators recently approved alemtuzumab to treat active relapsing-remitting multiple sclerosis, but the US Food and Drug Administration denied the drug for that indication last year.

Researchers at Cambridge University in London originally developed alemtuzumab as a laboratory tool to study the immune system. But within a short time, they recognized the biologic’s potential to treat the immune component of several diseases, and so it was moved to clinical investigation.

In 2001, the US Food and Drug Administration (FDA) approved alemtuzumab to treat B-cell chronic lymphocytic leukemia. Since that time, the drug has been used successfully in hundreds of thousands of cancer victims, as well as studied in many other conditions. Recently, European regulators approved alemtuzumab to treat active relapsing-remitting multiple sclerosis (RRMS).

Alemtuzumab’s approval for RRMS in Europe was based on findings from phase 2 and 3 trials that demonstrated superior efficacy over beta-interferon in reducing disability progression over 2—3 years. In those pivotal trials, 30% of patients developed secondary autoimmunity affecting the thyroid gland, while <3% developed immune thrombocytopenic purpura (ITP). More recently, an observational cohort study published in The Journal of Neurology, Neurosurgery, and Psychiatry described alemtuzumab’s longer-term efficacy and safety in active RRMS.

The study followed 87 patients treated with alemtuzumab from 1999 to 2012 to identify adverse events and pregnancy outcomes. More than one-third of the patients had failed previous disease-modifying therapy, and most were followed for approximately 7 years.

Slightly more than half of the patients required just 2 cycles of alemtuzumab therapy to stabilize their RRMS, and those who were diagnosed and treated early were most likely to respond robustly. Among the remaining patients, 36% received 3 cycles, 8% received 4 cycles, and 1% received 5 cycles, due to relapse. One cycle is defined as 5 days of alemtuzumab initially, with subsequent cycles shortened to 3 days.

Using a 6-month sustained accumulation of disability definition, the study authors found MS-related disability was improved or unchanged in 67.8% of the patients compared to baseline. Using area under the curve analysis, 59.8% of patients had overall improvement or disability stabilization.

Patients who relapsed early, had longer disease duration, or were older at the time of initial treatment were more likely to have poorer long-term disability outcomes — a finding that supports the early use of alemtuzumab.

As in the pivotal trials, secondary autoimmunity was the most frequent adverse event in the longer-term study with an incidence rate of 47.7%, most often affecting the thyroid gland. Only 3 patients developed ITP.

Alemtuzumab is not FDA-approved for highly active RRMS in the United States, as it was denied that indication by the regulatory agency in 2013. Since the average 7-year follow-up period of the current study identified no new safety concerns, Genzyme, the drug’s manufacturer, has resubmitted its application to the FDA based on the participants’ durable responses.

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