First therapy to receive breakthrough therapy status for this disease
Two large, phase 3 clinical trials demonstrated that targeting B-cells can have a significant impact on disease progression in patients with relapsing multiple sclerosis (MS).
In a head-to-head comparison of the investigational ocrelizumab (Ocrevus) with interferon beta-1a (Rebif), a greater proportion of patients who received ocrelizumab had no evidence of disease activity (NEDA) during the 96-week study than did patients who received interferon beta-1a, with the elimination of new or enlarging T2 lesions in nearly all patients after week 24.
Touted as a “wonderful achievement” by the study's lead investigator Anthony L. Traboulsee, MD, Director, UBC Hospital MS Clinic, Vancouver, British Columbia, Canada, these results signal a promising advancement in the treatment of patients with MS.
“This new, potential treatment has a very profound impact on preventing protocol-defined relapses. Over 96 weeks, approximately 80% of patients were free of relapses, 90% of patients were free of disability progression, and 95% of patients were free of new enhancing lesions, a classic biomarker of MS disease activity,” said Dr Traboulsee at the 2016 American Academy of Neurology annual meeting.
The OPERA I/II Clinical Trials
Although B-cells have been implicated in MS as components of pathogenesis, it was not known whether B-cell depletion would have an impact on disease activity, according to Dr Traboulsee. Ocrelizumab is a humanized monoclonal antibody that targets CD20, a protein located on the surface of some, but not all, B-cells.
In the OPERA I and OPERA II clinical trials, identical, phase 3, double-blind, double-dummy studies, patients were randomized in a 1:1 ratio to ocrelizumab 600 mg via intravenous infusion every 24 weeks or subcutaneous interferon beta-1a 44 µg 3 times weekly for 96 weeks.
Each study included 828 patients with early, relapsing-remitting MS. Approximately 70% of patients had previously untreated disease, proving a “very informative population,” said Dr Traboulsee.
NEDA—a composite measure of disease activity defined as no MS relapses, no confirmed disability progression, and no new or enlarging T2 lesions or gadolinium-enhancing T1 lesions—was analyzed, with magnetic resonance imaging (MRI) outcomes assessed at baseline, 24 weeks, 48 weeks, and 96 weeks.
In OPERA I, 81% of patients who received ocrelizumab did not have disease relapse compared with 68% of patients who received interferon beta-1a; the proportion of patients with no disability progression was 91% with ocrelizumab and 84% with interferon beta-1a. When these measures were combined, 76% of patients who received ocrelizumab were free of disease activity compared with 63% of patients who received interferon beta-1a.
Approximately 48% of patients in the ocrelizumab group in OPERA I had NEDA at 96 weeks versus 29% in the interferon beta-1a group, a 64% relative increase in preventing disease activity with ocrelizumab.
MRI analysis showed that 95% of patients using ocrelizumab had no evidence of serious disease activity versus 73% of patients using interferon beta-1a.
The results of OPERA II were nearly identical to OPERA I.
“These are very impressive numbers, especially when you consider that ocrelizumab was compared to an active therapy, not placebo. When we think of the early studies with interferon, the reduction was about 30% relative to placebo, so this is quite a steep improvement,” said Dr Traboulsee.
Overall, 63% of patients who received ocrelizumab were free of new T2 lesions during the study, Dr Traboulsee said, noting that after week 24, that number increased to 96%.
“We've made a giant leap forward over the past 20 years of treating MS. With a variety of mechanisms, we have increased the efficacy of treatment and expectations of patients with this disease,” said Dr Traboulsee. “Today, because of this novel approach through B-cell depletion, we can see a very highly effective treatment emerging for MS.”
On February 17, 2016, the FDA granted a breakthrough therapy status to ocrelizumab for the treatment of patients with primary progressive MS.
“Ocrelizumab is the first investigational medicine for MS to be granted Breakthrough Therapy Designation by the FDA,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development, in a statement. “With no approved treatments for primary progressive MS, ocrelizumab has the potential to address an important unmet need.”