Ocrelizumab Shows Positive Results in Treating PPMS
Genentech announced today that ocrelizumab, an investigational medicine for the long-term treatment of relapsing forms of MS, has also shown positive study results in their Phase III ORATORIO study with primary-progressive multiple sclerosis (PPMS). This is the first medication to show positive effects on disability with this form of the disease, which affects approximately 10 percent of the MS population.
To date, 13 disease-modifying therapies (DMTs) are approved for the long-term treatment of relapsing forms of MS, which exhibit the flare-ups and remissions often seen in MS. However, no treatments are available for individuals diagnosed with PPMS, whose MS steadily progresses without remissions.
According to Genentech, the Phase III ORATORIO study met its primary endpoint, showing that treatment with ocrelizumab significantly reduced the progression of clinical disability sustained for at least 12 weeks compared with placebo, as measured by the Expanded Disability Status Scale (EDSS). They also state that overall, the incidence of adverse events associated with ocrelizumab was similar to 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 placebo.
ORATORIO was a randomized, double-blind, and global multi-center trial that studied the effectiveness and safety of ocrelizumab in 732 people with PPMS. Every six months, two 300-mg infusions (for a total of 600 mgs) were given two weeks apart. Members of the treatment group were compared to a placebo group. The primary endpoint of this study was time to the onset of confirmed disability progression, defined as an increase in EDSS that is sustained for at least 12 weeks.
On July 1, 2015, MSAA posted the news item titled Ocrelizumab Shows Positive Results in Phase III Trials, which announced that ocrelizumab met both the primary and major secondary endpoints in the Phase III, OPERA I and OPERA II studies. These studies evaluated the effectiveness and safety of ocrelizumab in relapsing forms of MS. According to Genentech, when compared to Rebif, ocrelizumab showed “significant reductions” in: annualized relapse rate (ARR) over a two-year period; progression of clinical disability, as measured by the Expanded Disability Status Scale (EDSS); and number of lesions in the brain (areas of disease activity) as measured by MRI.
Ocrelizumab is an investigational, humanized monoclonal antibody designed to selectively target CD20-positive B cells. Genentech notes that these are a specific type of immune cell thought to be a key contributor to myelin and axonal damage, which can result in disability in people with MS. Based on preclinical studies, ocrelizumab binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved.
Genentech plans to submit data from all three of these studies to the United States Food and Drug Administration (FDA) in early 2016. If approved, this medication could potentially be used to treat not only relapsing forms of MS, but also primary-progressive MS, and would represent the first treatment available for this latter form of the disease.
MSAA Chief Medical Officer Dr. Jack Burks states, “This is very exciting news. Ocrelizumab is the first DMT with positive disability results. In addition, the safety data were similar to placebo controls. However, FDA approval will require intense scrutiny of these data. Effectiveness combined with safety is the magic formula, and we’ll see if the FDA agrees that ocrelizumab meets both requirements for approval in not only relapsing forms of MS, but in PPMS as well.”
For more 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 Wells Courtney, MSAA Senior Writer and Creative Director
Reviewed by Jack Burks, MD, MSAA Chief Medical Officer