Significant Percentage of MS Patients Receiving Alemtuzumab in Genzyme's Phase 2 Trial Remain Free of Clinically-Active Disease
Apr 14, 2010 (BUSINESS WIRE) -- Genzyme Corporation /quotes/comstock/15*!genz/quotes/nls/genz (GENZ 53.58, -0.06, -0.11%) today reported four-year follow-up data from its completed Phase 2 multiple sclerosis (MS) trial showing an estimated 71 percent of alemtuzumab treated patients remain free of clinically-active disease as much as three years after most patients received their last course of the investigational compound. The data were presented at the American Academy of Neurology annual meeting.
The CAMMS223 Phase 2 trial, first reported in the New England Journal of Medicine in 2008, compared alemtuzumab to the approved MS therapy Rebif(R) (interferon beta-1a) in early, active, relapsing-remitting multiple sclerosis (RRMS) patients who had received no prior therapy. In the trial, alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three times per week, every week for three years.
Results of the four-year review found:
-- an estimated 71 percent of alemtuzumab-treated patients were free of clinically-active disease, compared to 35 percent of patients taking Rebif (p<0.001). To be free of clinically-active disease, MS patients in the trial were both relapse-free and without progression of disability as measured by the Expanded Disability Status Scale (EDSS) throughout the course of the study;
-- an estimated 91 percent of alemtuzumab-treated patients were free of sustained accumulation of disability compared to 68 percent of patients taking Rebif; and
-- an estimated 77 percent of alemtuzumab-treated patients were relapse-free compared to 49 percent of patients taking Rebif.
"These early data may set a new bar for clinical outcomes in multiple sclerosis," said Omar Khan, MD, Professor of Neurology, Wayne State University School of Medicine, site principal investigator in the CAMMS223 Phase 2 trial.
Post-hoc analyses of the patients free from clinically-active disease were performed using data obtained from patients participating in CAMMS223. The dataset analyzed consists of the originally-planned three years of patient follow-up, additional continuous post-three-year follow-up, and prospective follow-up of patients who initially discontinued but returned to the study to participate in the risk management program. Roughly 15 percent of patients participating in the post-three-year follow-up used non-study MS disease modifying therapies. A sensitivity analysis that censored these patients found that the risk of relapse, sustained accumulation of disability, and free from clinically-active disease status favored alemtuzumab.
Alemtuzumab Mechanism of Action Data
Research suggests that in multiple sclerosis, T- and B-lymphocytes mistakenly attack the myelin sheath that protects nerve cells. These attacks can lead to disease progression and irreversible disability. The first detailed depiction of pharmacodynamic data from a large cohort of alemtuzumab treated relapsing-remitting MS patients (n=216) provided at AAN showed that alemtuzumab, in a selective fashion, targets T- and B-lymphocytes while largely sparing other immune system elements. The analysis also found that the targeted immune system cells begin to repopulate following treatment.
"We believe that alemtuzumab targets the immune system cells responsible for the cellular damage found in multiple sclerosis, while sparing other immune system elements," said Alasdair Coles, MD, Senior Lecturer, Department of Clinical Neurosciences, University of Cambridge, a lead investigator of the Phase 2 clinical trial and author of the leukocyte dynamics abstract.
Updated Safety Findings
Immune thrombocytopenic purpura (ITP), an autoimmune disease, was identified in six alemtuzumab treated patients and one Rebif patient in the Phase 2 trial. Symptoms of ITP went unrecognized in the first alemtuzumab case and led to the onset of a fatal cerebral hemorrhage. Five other alemtuzumab-related cases were subsequently diagnosed and all five patients achieved durable remission, both with and without treatment during the Phase 2 study. New follow-up data presented at AAN show that these five patients continue to have normal platelet counts, and ITP has not been identified more than 16 months following the last alemtuzumab cycle. There have been no additional or recurrent events of ITP reported in the Phase 2 trial to-date.
"In this study, alemtuzumab treated patients who experienced an ITP event and achieved remission have had no recurring episodes of ITP. The remissions were complete and durable," said abstract author Edward Fox, MD, PhD, Director of the Multiple Sclerosis Clinic of Central Texas, and a clinical site director for the Phase 2 and 3 trials.
Additional new follow-up data presented at AAN show that the alemtuzumab-treated patients who experienced an autoimmune adverse event still experienced clinical benefits. Alemtuzumab patients with autoimmune adverse events had a 78 percent reduced rate of relapse, and 66 percent reduced risk for sustained accumulation of disability, compared to Rebif patients. Updated four-year data from the Phase 2 trial found that approximately 28 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event. These events either normalized spontaneously or were managed using conventional therapies.
Genzyme is conducting two Phase 3 pivotal trials to evaluate alemtuzumab in the treatment of MS. Both trials completed enrollment in 2009. CARE-MS I, a randomized trial comparing alemtuzumab to Rebif, is studying early, active RRMS patients who have received no prior therapy. CARE-MS II, which also compares alemtuzumab to Rebif, is studying RRMS patients who relapsed while on other MS therapies. Patients who enrolled in those trials beginning in 2007 have completed the protocol-specified two years of follow-up and have begun to transfer into an extension trial. Data from the Phase 3 trials are expected to be available in 2011.