Update January 28, 2012
Update on Genzyme application to FDA for approval of alemtuzumab for treating relapsing MS. Genzyme announced that the FDA accepted the application for review, and that they expect FDA action on the application in the second half of 2013.
Published results of two large, phase III clinical trials confirm the ability of alemtuzumab (Genzyme, a Sanofi company) to significantly reduce relapse rates over two years over standard subcutaneous dosing of Rebif®
(interferon beta-1a, EMD Serono Inc. and Pfizer). One of the studies also suggests that alemtuzumab may significantly reduce worsening of disability. The results were previously reported at medical meetings, and lead authors Alasdair Coles, FRCP (University of Cambridge) and Jeffrey Cohen, MD (Cleveland Clinic) and colleagues have now published complete results of CARE-MS I
and CARE-MS II
in The Lancet (online November 1, 2012). Data were submitted to the U.S. Food and Drug Administration in an application for marketing approval and the application was accepted by the FDA for review in January 2013.
MS involves immune system attacks against brain and spinal cord tissues. Alemtuzumab is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells). It was originally approved for the treatment of B-cell chronic lymphocytic leukemia. Its ability to target immune cells led investigators to test its potential as a treatment for relapsing-remitting MS. Alemtuzumab is given by infrequent intravenous infusion -- for 5 days initially and for 3 days one year later.
During an earlier phase II study, dosing was temporarily suspended due to the occurrence of immune thrombocytopenic purpura (ITP), a rare condition in which low blood platelet counts can lead to abnormal bleeding. After the first cases of ITP occurred, one of which was fatal, Genzyme implemented a patient safety monitoring program which includes patient and physician education and regular contacts with patients. This program was also implemented for the phase III studies.
Because of the different routes of administration, patients and doctors were aware of which therapy the participants were on, but those who assessed their clinical condition and MRIs were not. In the CARE-MS I study, data were evaluated for 563 people with early, active relapsing-remitting MS, who had never received disease-modifying therapy to treat their MS and were randomly assigned to receive alemtuzumab or Rebif. Alemtuzumab was given by intravenous infusion for 5 days initially and for 3 days one year later. Those on Rebif received the standard dose of 3-times weekly subcutaneous injections. After two years the relapse rate for those on alemtuzumab was reduced by 55 percent compared to those on Rebif, and 8 percent of those on alemtuzumab had an increase in their EDSS score (a standard scale of physical disability) compared to 11 percent on Rebif – a difference that was not statistically significant.
The CARE-MS II study was a two-year trial comparing alemtuzumab to standard subcutaneous dosing of Rebif. Data were evaluated for 628 people with relapsing-remitting MS who had already been treated with another MS therapy but had experienced at least one relapse on that previous therapy. After two years, 35% of those on alemtuzumab experienced a relapse, versus 51% of those on Rebif, representing a 49.4% lower risk of relapses. In addition, 13% of those on alemtuzumab had an increase in their EDSS score, versus 20% of those on Rebif – a 42% difference that was statistically significant.
In both studies, those on alemtuzumab showed significant signs of reduction of disease activity as seen on MRI.
Most who were treated with alemtuzumab had mild to moderate infusion-related reactions, including headache, rash, nausea, and fever. Less than 20% of those treated with alemtuzumab developed autoimmune thyroid-related problems and up to 1% developed ITP. All cases were detected early through the monitoring program and managed with conventional therapies. The most common infections in those treated with alemtuzumab (all mild to moderate) were upper respiratory and urinary tract infections, sinusitis and herpes simplex infections.
Based on these positive studies, Genzyme has submitted an application to the U.S. FDA for marketing approval of alemtuzumab as a treatment for relapsing MS. The FDA’s review of these results and other data should help define the safety and promise of this as a potential new therapy for relapsing MS. The application was accepted by the FDA for review in January 2013.