Conference Coverage
BARCELONA—In people with primary progressive multiple sclerosis (MS), treatment with ocrelizumab may significantly reduce the progression of clinical disability sustained for at least 12 weeks, compared with placebo, according to results from a pivotal phase III study presented at the 31st Congress of ECTRIMS. In the study, which is called ORATORIO, clinical disability was measured by the Expanded Disability Status Scale (EDSS).
Ocrelizumab is an investigational, humanized monoclonal antibody designed to selectively target CD20-positive B cells. CD20-positive B cells are a type of immune cell thought to be a key contributor to myelin damage and axonal damage. Preclinical studies suggest that ocrelizumab binds to CD20 cell-surface proteins expressed on certain B cells, but not on stem cells or plasma cells, thus potentially preserving important functions of the immune system.
The ORATORIO trial was a randomized, double-blind, global multicenter study. Researchers administered placebo or 600 mg of ocrelizumab by IV infusion every six months to 732 people with primary progressive MS. The doses of ocrelizumab were given as two 300-mg infusions two weeks apart. The primary end point of the study was time to onset of confirmed disability progression, defined as an increase in EDSS that is sustained for at least 12 weeks.
Overall, the incidence of adverse events associated with ocrelizumab was similar to that of placebo. The most common adverse events were mild-to-moderate infusion-related reactions. The incidence of serious adverse events associated with ocrelizumab, including serious infections, was also similar to that of placebo.
“People with the primary progressive form of MS typically experience symptoms that continuously worsen after the onset of their disease, and there are no approved treatments for this debilitating condition,” said Sandra Horning, MD, Chief Medical Officer and head of Global Product Development for Genentech, the developer of the therapy. “Ocrelizumab is the first investigational medicine to show a clinically meaningful and statistically significant effect on the progression of disease in primary progressive MS.”
In addition to ORATORIO, the phase III clinical development program for ocrelizumab includes OPERA I and OPERA II, which are randomized, double-blind, double-dummy, global multicenter studies in people with relapsing forms of MS. The results of the studies appear to validate the hypothesis that B cells are central to the underlying biology of MS. Genentech plans to pursue marketing authorization for ocrelizumab in relapsing MS and in primary progressive MS. The company will submit data from the OPERA I and II studies and from the ORATORIO study to the FDA in early 2016.