Session at the 2014 Annual Meeting of the Consortium of Multiple Sclerosis Centers debates whether the side effects associated with alemtuzumab, a novel anti-CD52 monoclonal antibody, might ultimately prevent its approval for the treatment of multiple sclerosis, despite evidence of clinical effectiveness.
DALLAS -- May 31, 2014 — Serious questions remain regarding the side effects and benefits associated with the use of alemtuzumab for the treatment of multiple sclerosis.
The 2014 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and the Sixth Cooperative Meeting with Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) concluded Saturday with “Controversies in the Treatment of Multiple Sclerosis,” a debate-style session that focused on discussion of several hot-button issues in current practice. The third and final segment, “Controversy III: Alemtuzumab is Too Toxic to Use in Most Patients with MS,” featured a debate over the benefit vs. risk profile of alemtuzumab, an anti-CD52 monoclonal antibody that is currently approved for the treatment of several forms of leukemia and lymphoma and is being studied for the treatment of multiple sclerosis.
Late last year, the FDA rejected the drug for the treatment of multiple sclerosis, saying that more evidence from high-quality clinical trials was need regarding the benefits and risks of the drug in this patient population.
One participant in the debate session, Olaf Stüve, MD, PhD, said “there is a need for more effective yet safe therapies; currently available treatment options are only partially effective and have potentially life-threatening side effects.”
Stüve is associate professor in the Department of Neurology and Neurotherapeutics and associate professor in the Department of Immunology at University of Texas Southwestern Medical Center, and chief of the Neurology Section at VA North Texas Health Care Systems.
The clinical phase II CAMMS223 study (which was not an open-label study) compared alemtuzumab with interferon beta-1a in patients with early, active relapsing-remitting multiple sclerosis. Over five years of follow up, researchers found that treatment with alemtuzumab lowered the risk of sustained accumulation of disability by 72% compared with interferon beta-1a. Treatment with alemtuzumab also lowered relapse rate by 69% compared with interferon beta-1a. In the CARE-MS I trial, treatment with alemtuzumab led to a 55% risk reduction in relapses compared with interferon beta-1a.
Stüve also noted that in CARE-MS II the secondary co-primary endpoint (sustained accumulation of disability) was met and there was a 42% improvement in risk reduction in the alemtuzumab group compared with the interferon beta-1a group.
“Alemtuzumab is highly effective; with it patients can be treated early to prevent accumulation of disability,” he said.
“There is no need to treat patients long-term, sides effects are mostly mild to moderate, disease and organ specific, and a pharmacovigilance program could be established to screen patients,” said Stüve.
Fellow debater, Mitchell Wallin, MD, MPH, disagreed, pointing out that there are “serious GI side effects” associated with treatment with alemtuzumab, including abdominal pain and flushing.
Wallin is Clinical Associate Director of the Multiple Sclerosis Center of Excellence based in the Baltimore Veterans Affairs (VA) Medical Center/University of Maryland, and associate director of Clinical Care and associate professor of medicine at Georgetown University.
Safety issues potentially preventing the approval of alemtuzumab “include autoimmune cytopenias, nephropathy, serious infections, and malignancies,” said Wallin.
He noted there are also concerns over treatment adherence and challenges of maintaining long term injection. Adherence to self-administered disease-modifying therapies in multiple sclerosis has been the subject of several papers. Based on study results, between 12-87% of patients with multiple sclerosis do not adhere to their disease-modifying therapies.
In addition, because of the risk for life-threatening infections, rapid diagnosis of autoimmune cytopenias is imperative. He said the company had recommended monitoring complete blood count in patients.
If approved for the treatment of multiple sclerosis, the drug would have to have labeling regarding the risks, said Wallin.