Aaron E. Miller, MD, left, and Fred D. Lublin, MD, helped lead groundbreaking multiple sclerosis research.
Three multicenter Phase III trials in which Mount Sinai researchers played key roles have reported highly encouraging results for the investigational drug ocrelizumab in treating both primary progressive multiple sclerosis (MS), the most disabling form of the disease, as well as relapsing MS, the most prevalent form. Two of the three trials, known as OPERA I and OPERA II, were focused on relapsing MS. The third trial, ORATORIO, was aimed at primary progressive MS. The findings were published online Wednesday, December 21, 2016, in The New England Journal of Medicine (NEJM). “The results for ORATORIO were truly groundbreaking because we never before had a treatment that was proven to work with primary progressive MS,” says Aaron E. Miller, MD, Professor of Neurology at the Icahn School of Medicine at Mount Sinai and Medical Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai. “In the case of relapsing MS, we have had many options in the past, but this new treatment has extremely good efficacy and will probably be widely used for patients with the disease.”
MS is a complicated, often disabling, disease of the central nervous system that can produce a wide variety of neurological symptoms as it disrupts the flow of information within the brain and spinal cord, and between the brain and body. It afflicts an estimated 2.3 million people worldwide and 400,000 in the United States. Approximately 10 to 15 percent of this population is diagnosed with primary progressive MS, in which patients, instead of relapsing and recovering partly or fully, experience gradual deterioration from disease onset.
According to Dr. Miller, who served as principal investigator at Mount Sinai for ORATORIO, ocrelizumab significantly reduced the progression of clinical disability of primary progressive MS at both 12 and 24 weeks—a finding that prompted the NEJM to hail the trial in an editorial as a “landmark study in the field.”
Fred D. Lublin, MD, Saunders Family Professor of Neurology at the Icahn School of Medicine at Mount Sinai and Director of the Corinne Goldsmith Dickinson Center, was a member of the steering committee that designed and monitored ORATORIO. Dr. Lublin was also an author for OPERA I and OPERA II, which found that ocrelizumab resulted in 46 to 47 percent lower relapse rates than interferon beta-1a, a current leading treatment for relapsing MS. Ocrelizumab, from Genentech, a member of the Roche Group, was created to treat both forms of the disease. A humanized monoclonal antibody, ocrelizumab binds to CD-20 proteins on the surface of certain B cells, causing their depletion. B cells are believed to be a key contributor to attacks on the insulation and support around nerve fibers in the brain, spinal cord, and optic nerves that can lead to disability. Ocrelizumab is administered by intravenous infusion every six months.
“Every study brings us closer to a cure, and now we have opened the door to a whole new group: patients with primary progressive MS, whom we can more successfully treat,” Dr. Lublin says. “The next challenge is to see if we can select patients most likely to respond to this therapy.”