Ocrevus™ (Ocrelizumab) Phase III Trial Results Published
The results from three Phase III studies of the experimental medication Ocrevus™ (ocrelizumab) were published in the December 21, 2016 online issue of the New England Journal of Medicine (NEJM). Although initial findings had been presented at the 2015 ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis) Annual Meeting and other MS conferences, the published information includes the full data from the OPERA I and OPERA II studies, for relapsing multiple sclerosis (RMS), and the ORATORIO study, for primary-progressive multiple sclerosis (PPMS).
In the studies, Ocrevus showed positive results in treating both RMS and PPMS. In addition to its effectiveness in RMS when compared to an approved, highly effective MS treatment, this is the first time that a medication has been shown to be effective in delaying disability progression and slowing disease activity in PPMS (when compared to placebo). This latter type of the disease is characterized by a steady accumulation of symptoms, versus sudden flare-ups and remissions. Presently, no approved treatment is available for individuals with PPMS.
Specific Study Results in RMS
In the two identical Phase III trials in relapsing forms of MS (RMS), OPERA I and OPERA II, Ocrevus showed greater effectiveness when compared to high-dose Rebif® (interferon beta-1a). In the data to follow, all figures are given for OPERA I first, followed by those for OPERA II, respectively.
In these studies, Ocrevus reduced the annualized relapse rate (ARR) by 46 and 47 percent over the two-year period. Confirmed disability progression (CDP) sustained for periods of both 12 and 24 weeks, was reduced by 43 percent and 37 percent for both time periods and in both studies.
In terms of magnetic resonance imaging (MRI) findings, T1 gadolinium-enhancing lesions were reduced by 94 percent and 95 percent in both trials, and the total number of new and/or enlarging hyperintense T2 lesions were reduced by 77 percent and 83 percent. At 96 weeks, Ocrevus increased the proportion of patients who showed no evidence of disease activity (NEDA) by 64 percent and 89 percent.
Specific Study Results in PPMS
The ORATORIO Phase III trial compared Ocrevus to placebo in individuals with primary-progressive MS (PPMS). In this study, the risk of confirmed disability progression (CDP) was reduced by 24 percent for at least 12 weeks and 25 percent for at least 24 weeks. The time required to walk 25 feet (Timed 25-Foot Walk) was reduced by 29 percent at 120 weeks.
In terms of MRI findings, the total volume of brain hyperintense T2 lesions was reduced by 3.4 percent over the 120-week time period. This was in contrast to a 7.4-percent increase experienced by individuals with PPMS in the placebo group. From week 24 to week 120, the rate of whole brain volume loss was reduced by 17.5 percent compared with placebo.
General Information on Ocrevus
The makers of Ocrevus, Genentech, a member of the Roche group, have submitted this medication to the United States Food and Drug Administration (FDA) for the treatment of these two types of MS. It’s the first drug to be submitted for the treatment of both RMS and PPMS. A decision on the approval of Ocrevus is expected on March 28, 2017. Ocrevus is not yet approved in any country, but is also currently under review by the European Medicines Agency (EMA).
Ocrevus is a humanized monoclonal antibody designed to selectively target CD20-positive B cells. This is a specific type of immune cell that is an important contributor to the MS-disease process. Ocrevus is given via intravenous (IV) infusion every six months.
Genentech reports that the most common adverse events seen with this medication were mild to moderate infusion-related reactions and infections, while adverse events were similar between the different groups in each study. Open-label extension studies in both RMS and PPMS continue to monitor and analyze the safety of Ocrevus.
For More Information
Please see MSAA’s online news article, “FDA Extends Review of Ocrevus™ (ocrelizumab)” for additional details.
For specific questions about Ocrevus, please contact Genentech’s Trial Information Support Line (TISL) at (888) 662-6728, or their Patient Resource Center at (877) 436-3683.
For general information or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.
Written by Susan Courtney, MSAA Senior Writer
Reviewed by Jack Burks, MD, MSAA Chief Medical Consultant