Campath (alemtuzumab) and MS Patients - Positive Phase 2 Results
As researchers continue to investigate more effective and safe treatments, we MS patients will continue to read positive reports of clinical trial results and continue to hope for better treatments and possibly a cure someday. This week was one of those weeks. Positive results from a Phase IIb trial comparing alemtuzumab (Campath-1H) with interferon beta-1a (Rebif) was announced by Genzyme Corporation and Bayer HealthCare Pharmaceuticals.
Alemtuzumab is a DNA-derived humanized monoclonal antibody that binds to a specific target, CD52, on some cells of the immune system, including both T and B lymphocytes, as well as monocytes, macrophages, natural killer cells and eosinophils, but not on neutrophils. When alemtuzumab binds to these cells, it triggers their destruction by the immune system. It is the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-cell Chronic Lymphocytic Leukemia (B-CLL), a malignant disease of B-lymphocytes. (see report in Bio-Medicine, May 02, 2007)
Other monoclonal antibody therapies in use or in clinical trials for MS include natalizumab (Tysabri) which is FDA-approved for relapsing forms of MS and Crohn’s disease, daclizumab (Zenapax) which is FDA-approved to prevent rejection of kidney transplants, and rituximab (Rituxan) which is FDA-approved for non-Hodgkins lymphoma and rheumatoid arthritis.
The current study was a phase 2 trial conducted in patients with early active RRMS (less than 3 years since diagnosis) who had not used any disease-modifying drugs. The cumulative number of relapses over time was reduced by 74% in patients receiving alemtuzumab versus those who received interferon, and the time to sustained accumulation of disability (SAD) was reduced by 71% with alemtuzumab, compared with interferon (P < .0001 for both). (see Medscape Medical News, September 24, 2008)
As reported in ScienceDaily, the investigators showed that many individuals in the trial who received alemtuzumab recovered some of their lost functions and so were less disabled after three years than at the beginning of the study, in contrast to worsening disability in the interferon beta-1a treated patients. These findings suggest that alemtuzumab may allow damaged brain tissue to repair, enabling the recovery of neurologic functions lost following poor recovery from previous MS attacks.
"The ability of an MS drug to promote brain repair is unprecedented. We are witnessing a drug which, if given early enough, might effectively stop the advancement of the disease and also restore lost function by promoting repair of the damaged brain tissue," says Dr Alasdair Coles, University Lecturer at the Department of Clinical Neurosciences, University of Cambridge who coordinated many aspects of the study.
Adverse effects were a concern with alemtuzumab, however. The most common side-effect was the development of autoimmune thyroid dysfunction which affected 23% of those on the new drug versus 3% of those on interferon. Immune thrombocytopenic purpura (ITP) occurred in 2.8% of alemtuzumab patients, a condition which lowers blood platelet levels and increases risk of hemorrhage. One patient in the trial died of the condition. But both of these conditions can be monitored and treated providing that diagnosis is made quickly enough, says Dr. Coles. (see Guardian News, October 23, 2008)
The results of this 36-month study are published in the New England Journal of Medicine (abstract available here)
Phase 3 trials are currently under way and still recruiting (see Genzyme and Clinical Trials here and here). If Phase 2 results are confirmed, researchers are excited that this could be a powerful drug when used early enough in the disease process.