Positive Pivotal Study Results with Ocrelizumab for Two Forms of Multiple Sclerosis

A pair of phase III studies revealed positive efficacy and safety outcomes for ocrelizumab, and this could be a game-changer for patients with multiple sclerosis (MS).

It’s believed that B cells influence the biology of MS in multiple ways. Ocrelizumab works by selectively depleting CD20+ (transmembrane protein) B cells without harming immunity provided by plasma cells. Stephen L. Hauser, MD, from the University of California, spoke about the “pivotal trial data” at the 31^st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2015) in Barcelona, Spain.

OPERA I and II were identical, double-blind studies which included 821 and 835 patients, respectively, with relapsing forms of MS. All patients were ages 18 to 55, had an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 at baseline, and at least two documented clinical attacks within the previous two years or one within one year before screening. Other notable factors were that 66% of the patients in both studies were female and the average duration since initial symptom onset was 6.48 years — with the average MS diagnosis being 3.77 years.

The patients were assigned either ocrelizumab 600 mg through intravenous infusion every 24 weeks or interferon (IFN)-β-1a 44 µg subcutaneously three times per week for 96 weeks — both considered “high dose.” If patients completed the trial, they had the option to enter an open-label extension trial to continue treatment.

“I would say first that adherence to treatment was good,” Hauser explained during the presentation. “Remarkably, more than 95% of patients opted for the open-label trial.”

Ocrelizumab proved to have a highly statistically significant effect on confirmed disability progression (CDP) at 12 and 24 weeks. It cut the risk of CDP by 40%. Further observation revealed a dramatic reduction in both glial activation and T1 lesions, which were consistent and sustained results in both trials.

When compared to IFN, the ocrelizumab group had 77% lower T2 lesions in OPERA I, with similar results in OPERA II. Hauser noted that while the reduction in new and enlarged T2 lesions was significant, the outcomes were incomplete. In addition, there was an average relapse rate in both studies of 1.56. Nevertheless, ocrelizumab showed significant, independent effects on risk cut in these areas.

One of the exploratory endpoints explored brain volume loss. In OPERA I, ocrelizumab was able to reduce the process by 23.5% and in OPERA II by 23.8%.

More than half of the patients had events during the trials, which Hauser claimed was not surprising. Many of them can be attributed to new or enlarged T2 lesions prior to the 24-week point of the studies.

Ocrelizumab and IFN showed a similar safety profile and there were low levels of serious adverse effects in both groups. Serious infections occurred in 1.3% on ocrelizumab and 2.9% on INF.

“As you might expect, there were more infusion reactions in the ocrelizumab group,” Hauser said. Most of the infusion-related reactions were mild to moderate in severity and occurred after the first dose.

“In conclusion, in both OPERA I and OPERA II, ocrelizumab was effective in relaxing MS,” Hauser wrapped up. The findings suggest that CD20+ B cells are a good target for MS treatment.