Besides safety, the other major issue at the meeting was the disagreement between the FDA and Genzyme over the design of the clinical trials, which were open label, with clinicians and patients unblinded to the treatment. Dr. Billy Dunn, acting deputy director of the FDA’s division of neurology products, said that the FDA reviewers believed that bias was "pervasive" in these studies but that the impact the bias had on efficacy results was unclear.
There was a large difference in dropout rates between the treatment groups after randomization before the initiation of treatment between the two groups – almost 13% among those assigned to interferon beta-1a vs. 2% among those assigned to alemtuzumab in one of the studies. This could be explained by patients assigned to interferon beta-1a wanting the newer drug and was among the evidence FDA reviewers said illustrated the bias that was introduced into the studies because of unblinding.
In other questions posed by the FDA, most of the panel voted that the company had not provided substantial evidence that alemtuzumab had a beneficial on disability (14-2 with 2 abstentions) and that the two phase III studies were not adequate and well controlled (11-6 with 1 abstention).
Genzyme, a Sanofi company, is conducting an extension study of alemtuzumab in about 1,300 patients (including those in the three studies) that is evaluating safety and efficacy for up to 5 years, which includes patients now being treated in Europe.
A decision on approval is expected in December. The FDA usually follows the recommendations of its advisory panels. Members have been cleared of potential conflicts; occasionally, a panelist is given a waiver for a potential conflict, but not at this meeting.