Ocrelizumab reduced both relapses and disability progression to a significantly greater extent than did interferon beta-1a in patients with relapsing-remitting multiple sclerosis in two large phase III trials.
The selective B-cell–targeting monoclonal antibody cut the annualized relapse rate by almost half when compared against interferon beta-1a and significantly reduced the risk of confirmed disability progression at both 12 and 24 weeks, Dr. Stephen Hauser reported at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis in Barcelona.
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Ocrelizumab, a humanized monoclonal antibody that selectively targets CD20-positive B cells, succeeded on secondary outcomes as well, reducing T1 gadolinium-enhancing lesions by more than 90%, and the emergence or enhancement of T2 hyperintense lesions by 80%, said Dr. Hauser, chair of neurology at the University of California, San Francisco.
The data are from two identically designed phase III trials conducted by Genentech. OPERA 1 and OPERA 2 enrolled 1,656 patients with relapsing-remitting multiple sclerosis (RRMS). They were randomized to either 600-mg ocrelizumab IV infusions every 24 weeks plus placebo subcutaneous injections three times weekly or to 44-mcg subcutaneous injections of interferon beta-1a (Rebif) thrice weekly plus placebo IV infusions every 24 weeks. Both studies were conducted for 96 weeks.
The patients were a typical RRMS cohort: young (mean 37 years) and mostly women (66%). The mean baseline score on the Extended Disability Status Scale was 2.77 and the mean time since diagnosis about 4 years. Patients had about 1.5 relapses in the first and second year before entering the studies; about one-third (595) were naive to treatment.
Compared with interferon beta-1a, ocrelizumab reduced the annualized relapse rate by 46% in OPERA 1 and 47% in OPERA 2. It also posted 43% and 37% risk reductions in confirmed disability progression sustained for both 12 and 24 weeks.
On imaging measures, ocrelizumab bested interferon beta-1a as well. It conferred a 94% and 95% reduction in the total number of T1 gadolinium-enhancing lesions and a 77% and 83% reduction in the total number of new and/or enlarging hyperintense T2 lesions. An exploratory analysis suggested that the drug reduced the rate of whole brain volume, compared with interferon beta-1a.
A pooled safety analysis comprised 83% of the entire study population. Adverse events were similar in both treatment groups overall. Infusion reactions were significantly more common with ocrelizumab than with interferon beta-1a (34% vs. 9.7%). There were similar rates of serious adverse events, including serious infections (6.9% and 8.7%), and there were no cases of progressive multifocal leukoencephalopathy.
Long-term safety investigations are still ongoing, Genentech’s Dr. Peter Chin said in an interview. Ocrelizumab was originally developed by Roche and Biogen for rheumatoid arthritis. But in 2010, the companies halted development of the drug when an interim safety analysis found a significantly increased incidence of serious infections.
While Genentech will keep monitoring for those problems, they may be less likely to develop in MS patients than in patients with RA, said Dr. Chin, principal medical director for Genentech-Roche Global Neuroscience Development.
“Patients with RRMS are typically younger and, overall, healthier, than those with RA, without many of the comorbidities that predispose them to opportunistic infections,” he said. “They also tend to be taking concurrent immunosuppressive drugs, which increases their risk in a way we wouldn’t see in most MS patients.”
Dr. Hauser noted that he has received financial support from F. Hoffmann-La Roche, Symbiotix, and Bionure.