Date: 2011-04-05
Type of information: Results
phase: 2
Announcement: results
Company: Genzyme (USA - MA), a Sanofi company (France)
Product: alemtuzumab
Action
mechanism: This humanized monoclonal antibody targets the cell-surface glycoprotein CD52, which is often expressed on T- and B-lymphocytes. Preliminary research suggests that alemtuzumab depletes the T- and B-cells that may be responsible for the cellular damage in MS, while potentially sparing other cells of the immune system. Early alemtuzumab research has also suggested a distinctive pattern of lymphocyte reconstitution in patients following treatment.
Disease: multiple sclerosis
Therapeutic area: Autoimmune diseases - Neurodegenerative diseases
Country:
Trial
details: In the Phase 2 trial, 334 patients with early active relapsing-remitting multiple sclerosis were randomized to treatment with alemtuzumab at one of two dose levels, or to the approved MS therapy Rebif® (high dose interferon beta-1a). 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. The majority of alemtuzumab treated patients last received the investigational drug at Month 12.
The trial successfully met its two primary endpoints, reduction in relapse rate and reduction in the rate of sustained accumulation of disability.
Patients were strongly encouraged to continue for two additional years of follow-up beyond the original three years of the study. Sixty-eight percent of alemtuzumab patients participated in the follow-up program, and 60 percent were evaluated at 60 months. Forty-two percent of Rebif patients participated in the follow-up program, and 35 percent were evaluated at 60 months. Rater-blinded disability scores were assessed quarterly and relapses as-needed. A sensitivity analysis adjusted for patients receiving alternative disease-modifying therapy during the follow-up period, as well as for retreatment with alemtuzumab.
Latest
news: Genzyme, a subsidiary of sanofi-aventis Group has reported additional five-year patient data from its completed Phase 2 multiple sclerosis (MS) trial showing that nearly two-thirds of alemtuzumab treated patients remained free of clinically-active disease as much as four years after most patients received their last course of the investigational drug. The data were presented at the American Academy of Neurology's 63rd Annual Meeting.
“The improvements seen with alemtuzumab treatment as compared with interferon beta are encouraging.”
Results of the five-year review showed:
• an estimated 65 percent of alemtuzumab-treated patients were free of clinically-active disease, compared to 27 percent of patients taking Rebif (p<0.0001). To be free of clinically-active disease, MS patients in the trial were both relapse-free and without a sustained increase in disability as measured by the Expanded Disability Status Scale (EDSS) through five years;
• an estimated 72 percent of alemtuzumab-treated patients were relapse-free compared to 41 percent of patients taking Rebif; and
• an estimated 87 percent of alemtuzumab-treated patients were free of sustained accumulation of disability compared to 62 percent of patients taking Rebif (previously reported).
Two pivotal Phase 3 studies investigating alemtuzumab, CARE-MS I and II, are currently ongoing. Top-line results from these trials are expected to be available respectively early in the third quarter of 2011 and in the fourth quarter of 2011. The company expects to file for U.S. and E.U. approval in early 2012, and has been granted fast track status by the FDA for this submission.
