FDA Rejects Multiple Sclerosis Drug Lemtrada After Disagreement Over Testing Methods

The FDA rejected Lemtrada (alemtuzumab), a multiple sclerosis (MS) drug by Genzyme, despite the medication having been approved in Canada, Europe and Australia. The decision from the FDA turned on a disagreement over the trial methods used. Lemtrada, which works in a significantly different way from other MS drugs, eliminates with every annual treatment the B cells and T cells that cause harmful immune responses in MS patients.

Typically, the FDA expects patients in drug trials not to know whether they are receiving the control treatment or the active treatment in the study, in order to avoid bias in the results. However, Genzyme, having looked to both the FDA and European regulators when designing the Lemtrada trial, decided not to blind the patients in the trial, but the physicians rating the patients in the trial. The reason for the decision, according to Genzyme, is that blinding the patients would have been useless, as Lemtrada and the control drug, Rebif by EMD Serono, had dramatically different methods of administration. Lemtrada is administered intravenously over five days once a year, and Rebif is injected by the patient three times a week on an oongoing basis. Further, Rebif causes flu-like side effects that are not experienced by patients receiving Lemtrada.

The FDA contends that Genzyme should have used a testing method called a “double-dummy” trial, in which all patients would have received both annual intravenous treatment and injections three times per week, with one treatment being a placebo. However, Genzyme countered that such a method would also be futile, as patients would know which drug they were receiving because of their immediate reactions to the treatments.

“We strongly believe that the clinical development program, which was designed to demonstrate how Lemtrada compares against an active comparator as opposed to placebo, provides robust evidence of efficacy and a favorable benefit-risk profile,” said Dr. David Meeker, the CEO of Genzyme. “This evidence was also the basis for the approvals of Lemtrada by other regulatory agencies around the world.

Some fear that MS patients in the US will turn to Canada to obtain Lemtrada, which requires close monitoring by a physician to ensure the recovery of the patient’s immune system. Without FDA approval of Lemtrada, physicians in the U.S. would not be properly trained on the possible health risks of the drug, and “some patients could die,” said Chief Medical Officer of the Multiple Sclerosis Association of America Jack Burks.

Genzyme plans to appeal the FDA’s decision.