End of December 2013, alemtuzumab, a monoclonal antibody for multiple sclerosis (MS) with an immunomodulator action targeting CD52 receptors and inducing decrease counts of lymphocytes B and T was rejected by the Food and Drug Administration, as the registration dossier had not shown convincing evidence that the benefit of the drug would overreach its safety risks. The question is in fact more global as immunomodulators constitute the majority of the newly registered drugs and drugs in clinical development for MS. The knowledge accumulated by the time these drugs are registered does not suffice to ascertain their safety profile. The safety issue raised by the FDA extends beyond alemtuzumab and actually concerns the benefit-risk of the whole class of immunomodulators/immunosuppressors which are now proposed for the treatment of RRMS and at least for certain of them such as fingolimod, natalizumab, ocrelizumab or siponimod are tested in progressive forms of MS. Not surprisingly, the European Medicine Agency (EMA) in its revised draft guidelines for MS treatments. Following these two drugs, much stronger immunomodulators were developed, the first being natalizumab followed by fingolimod and more recently teriflunomide and fumarate. These treatments have direct impact on the lymphocyte response, circulation or penetration in the tissues.
Francois Curtin, Benefit-Risk of Immunomodulators in Multiple Sclerosis. Alemtuzumab
Last date updated on June, 2014