Alemtuzumab Results Published: Reduced MS Relapses and Accumulation -- Phase 3 Trials Recruiting Patients

Treatment with alemtuzumab (Genzyme Corporation) reduced the accumulation of disability and the frequency of relapses in people with earlyrelapsing-remitting MS, compared toRebif®(interferon beta-1a, EMD Serono, Inc. and Pfizer, Inc.). Those taking alemtuzumab had a 74% reduction in the risk of MS relapse compared with those on Rebif, and a 71% reduction in the risk for sustained accumulation of disability. Those on alemtuzumab, an immune-suppressing monoclonal antibody, experienced adverse events more frequently, including immune thrombocytopenic purpura (a serious bleeding disorder), thyroid adverse events, and infections. The results, originally reported at medical meetings, have now been published (New England Journal of Medicine2008 359;17: 30-45), and two Phase 3 trials arecurrently recruiting participantswith relapsing-remitting MS.

Background and Details

Alemtuzumab is a humanized monoclonal antibody directed at CD52 (a protein on the surface of immune cells) that is currently approved by the U.S. Food and Drug Administration as a single agent for treatment of patients with B-cell chronic lymphocytic leukemia. Its ability to target immune cells has led investigators to test its potential as a treatment for relapsing-remitting MS.

Drs. D. Alastair Compston, Alasdair J. Coles (University of Cambridge, UK) and colleagues have now published results of phase 2 clinical trial that compared high and low doses of alemtuzumab (given by IV infusion over three to five days once a year) with Rebif, a standard MS therapy, in 334 people with early relapsing-remitting MS who had never taken any other disease-modifying therapies. The primary outcomes were the time to sustained accumulation of disability and the rate of relapse. Those in the alemtuzumab groups were slated to receive two to three cycles of the annual infusion. However, 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. A total of six alemtuzumab-associated ITP cases were identified and, when necessary, promptly treated.

Most of those on alemtuzumab received their second infusion cycle (207 out of 223 total), but fewer went on to receive a third cycle (46 out of 223). The results reported in this publication follow the participants out to 36 months of the study.

Results

The results were nearly the same for the two doses of alemtuzumab, so the data for patients receiving this drug were pooled for the comparison with Rebif. After thirty-six months, those taking alemtuzumab experienced significant reductions in the risk of MS relapse compared with those taking Rebif (74% reduction, with an annualized relapse rate of 0.36 for Rebif versus 0.10 for alemtuzumab) as well as significant reductions in the risk for progression of disability compared with those taking Rebif (71% reduction). Among secondary outcomes that were measured, significantly more of those on alemtuzumab remained relapse-free at 36 months (52% for Rebif and 80% for alemtuzumab). In addition, the mean disability score (EDSS) for those on alemtuzumab improved slightly (by 0.39 point) while the mean score of those on Rebif declined slightly (by 0.38 point). Among other side effects reported in the Phase 2 study, patients who received alemtuzumab were more likely to develop thyroid disease and mild to moderate infections (i.e., infections requiring no specific medical intervention or requiring only oral medication). Thyroid problems are reported to have been easily detected and treated. Patients who received Rebif experienced injection site reactions, fatigue, flu-like illness, headache and abnormal liver function tests.

Comment

“We are pleased to see potential new treatment options move positively through the MS pipeline,” said John R. Richert, MD, executive vice president for research and clinical programs at the National MS Society. “We look forward to results from the Phase 3 studies now getting underway, which will help determine if this treatment can be used safely and effectively in people with MS.”

Two Phase 3 trials of alemtuzumab, supported by Genzyme Corporation and Bayer Healthcare Pharmaceuticals, arecurrently recruiting participants.

Rebif is a registered trademark of EMD Serono, Inc. and Pfizer, Inc.