RESEARCH UPDATE: Genzyme’s Alemtuzumab shows being effective in patients with highly active multiple sclerosis (MS)

ORLANDO — The investigational drug alemtuzumab was effective in patients with highly active multiple sclerosis (MS), to the point that disease activity vanished in one-quarter, a researcher said here.

A subgroup analysis of data from the pivotal CARE-MS II trial, involving patients with multiple recent relapses and MRI-detected gadolinium-enhancing lesions at study entry, found an annualized relapse rate of 0.33 during the first 2 years of alemtuzumab (Lemtrada) treatment, compared with 0.65 for patients receiving interferon-beta-1a (Rebif), said Stephen Krieger, MD, of Mount Sinai School of Medicine in New York City.

The 51% reduction in relapse rate (P<0.0001) was virtually identical to the 49% decrease seen in the full CARE-MS II datareported last year, Krieger told attendees at the joint meeting of the Consortium of Multiple Sclerosis Centers and the Americas Committee for Treatment and Research in Multiple Sclerosis.

The most stringent criteria for response — no relapses, no sustained accumulation of disability, and no new gadolinium-enhancing lesions or new or enlarging T2 lesions — were met by 24.2% of patients receiving alemtuzumab, compared with none of the interferon-beta control group, Krieger said.

Alemtuzumab is an anti-CD52 monoclonal antibody formerly sold as a cancer drug under the name Campath. In MS, it is believed to induce a shift in immune responsiveness to downregulate the T cell-mediated attack on myelin in the nervous system.

In the MS clinical trials, alemtuzumab was administered by infusion in an initial 5-day course, followed by a second 3-day course a year later. Two phase III trials testing alemtuzumab against interferon-beta-1a have been conducted: CARE-MS I in treatment-naive patients, and CARE-MS II in patients showing continued disease activity while on an approved disease-modifying MS drug.

Of the 667 patients in the latter study, 145 had what the investigators called highly active disease at enrollment — at least two relapses in the previous year plus at least one gadolinium-enhancing lesion. Presumably, these would represent a more treatment-resistant group of patients.

The subgroup analysis generally supported that view. Response rates to both drugs were lower in the high-activity cohort than in the overall CARE-MS II data, in which the annualized relapse rates after 2 years were 0.26 and 0.52 for alemtuzumab and interferon, respectively.

Alemtuzumab consistently outperformed interferon in every other outcome measures Krieger reported for the highly active subgroup during the 2-year study (all P<0.001):

Safety findings were similar in the subgroup to what had been seen in other patients, Krieger said. Serious infections were somewhat more common with alemtuzumab (seen in 3.9% of patients, compared with 2.4% of the interferon control group). Serious infusion reactions were common, an effect not seen with interferon, which is given by subcutaneous injection.

No cases of autoimmune thrombocytopenia were seen in the analysis, Krieger said. Overall, he said, adverse effects with alemtuzumab were not “unexpectedly disproportionate” in the highly active subgroup.

There was one death in the subgroup — a patient in the alemtuzumab arm who died in a traffic accident.

Alemtuzumab’s developer, the Genzyme unit of Sanofi, has applied for U.S. marketing approval. A decision is expected this fall.