October 1, 2015
Promising results from ocrelizumab clinical trial announced by Genentech for people with primary progressive MS
Biotechnology company Genentech, member of Roche group, has just announced results from a phase III clinical trial evaluating the efficacy and safety of ocrelizumab for people living with primary progressive multiple sclerosis (MS). Ocrelizumab is the humanized form of Rituximab, a mouse antibody that binds to CD20, a protein that is expressed on the surface of white blood cells known as B cells that are involved in the disease process. Ocrelizumab has met with some success in the treatment of relapsing-remitting MS (see OPERA I and OPERA II clinical trials), and the humanized antibody is less likely to cause infusion reactions.
The trial, dubbed ORATORIO, is a multicentre, double-blind, randomized, placebo-controlled, Phase III clinical trial designed to investigate the effectiveness of ocrelizumab in reducing clinical disability progression in people living with primary progressive MS. 732 participants with primary progressive MS were enrolled in the trial. Some of the participants were randomly selected to receive ocrelizumab, which was administered via two intravenous infusions of 300 mg given two weeks apart. The remaining participants we randomly selected to receive a mock treatment (placebo).
Treatment with ocrelizumab significantly reduced overall clinical disability progression (defined as an increase in the Expanded Disability Status Scale sustained for at least 12 weeks) compared to the placebo group. The occurrence of adverse events was similar to those reported in the placebo group, and mainly consisted of mild-to-moderate infusion reactions.
According to Roche group, ocrelizumab is the first investigational pharmaceutical compound to show both “clinically meaningful and statistically significant” effects in reducing disability progression in people living with primary progressive MS. The positive results reported in the trial, as well as those seen in trials for relapsing-remitting MS, further demonstrate that B cells play a major role in the underlying disease processes of MS. The MS Society of Canada and MS Scientific Research Foundation currently fund a Canadian collaborative study focused on B cells and progressive MS.
The ocrelizumab clinical trial results will be presented at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Barcelona, Spain as a late-breaking abstract on Saturday, Oct. 10.
Professor Xavier Montalban from Barcelona, Spain presented results from the ORATORIO trial. He showed that treatment with ocrelizumab via 2 intravenous infusions of 300mg two weeks apart significantly reduced the risk of progression of clinical disability sustained for at least 12 weeks by 24% compared with placebo, as measured by EDSS.
Additionally, ocrelizumab was superior to placebo in a number of secondary endpoints, for example it significantly reduced the risk of progression of clinical disability for at least 24 weeks by 25% and the time required to walk 25 feet (measured using the Timed 25-Foot Walk test) over 120 weeks by 29%. Ocrelizumab decreased the volume of T2 lesions by 3.4% over 120 weeks, compared to placebo which increased T2 volume by 7.4%. Ocrelizumab reduced the rate of whole brain volume loss over 120 weeks by 17.5% compared to placebo. Adverse events were similar in the treatment and placebo groups. The most common adverse event in the treatment group was infusion-related reactions.
This positive data positions ocrelizumab as a promising candidate for the treatment of primary progressive MS.