FDA Expedites Review of Ocrelizumab for the Treatment of PPMS
The United States Food and Drug Administration (FDA) has granted “Breakthrough Therapy Designation” for ocrelizumab, an experimental medication presently under investigation for the treatment of primary-progressive multiple sclerosis (PPMS). At this time, no treatments are available for this less-common form of MS. With this designation, the FDA affirms: (1) the medication would be used to treat a serious condition; (2) preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies; and (3) the review process would be expedited to within 60 days. Please note that ocrelizumab has not yet been submitted to the FDA for approval. As mentioned later in this article, ocrelizumab is expected to be submitted sometime during the first half of 2016.
In contrast to relapsing-remitting MS (RRMS) – the most-common type of multiple sclerosis affecting 80 to 85 percent of people diagnosed with MS – about 10 percent of the MS population is diagnosed with PPMS. Individuals with PPMS experience a steady worsening of symptoms from the start, without the periodic relapses and remissions experienced by people with RRMS. While 13 disease-modifying therapies are currently approved for relapsing forms of MS, no long-term treatments have been approved for PPMS.
Genentech, a member of the Roche group, is the company developing ocrelizumab. They have submitted the brand name Ocrevus™ to the FDA for this investigational medication, noting that this is the first drug for MS that has been designated as breakthrough therapy by the FDA.
Ocrelizumab is an investigational, humanized monoclonal antibody designed to selectively target CD20-positive B cells. Genentech explains 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. In Phase III trials, ocrelizumab was given every six months in two, 300-mg intravenous (IV) infusions. These two infusions were separated by two weeks.
According to Genentech, the breakthrough designation is based on positive results from the pivotal Phase III ORATORIO study. Top-line results from this study were presented at the 31st congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in October 2015.
These results stated that the trial met its primary endpoint, showing that treatment with ocrelizumab in PPMS significantly reduced the progression of clinical disability sustained for at least 12 weeks compared with placebo. Walking speed, as measured by the timed 25-foot walk, was improved by 29 percent. The incidence of adverse events associated with ocrelizumab was similar to placebo; the most common adverse events were mild-to-moderate infusion-related reactions. Additionally, MRI hyper-intense T2 lesions were actually reduced by ocrelizumab, and brain-volume loss as viewed on MRI was reduced by 17.5 percent. Please refer to the “Progressive MS” section of MSAA’s news article, “Highlights from the 2015 ECTRIMS Meeting,” for more information.
Readers should note that this breakthrough designation with the expedited review period has only been granted by the FDA for the one indication, which is for the long-term treatment of PPMS, as studied in the ORATORIO trial. Genentech is also studying this medication for the long-term treatment of relapsing forms of MS in the OPERA I and OPERA II trials. They plan to submit data from all three of these Phase III studies to the FDA in the first half of 2016, seeking approval for ocrelizumab in both PPMS and relapsing forms of the disease.
MSAA Chief Medical Officer Dr. Jack Burks states, “This is very exciting news. Ocrelizumab is the first disease-modifying therapy with positive disability results in PPMS. 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 PPMS.”
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.
Updated February 19, 2016
Written by Susan Wells Courtney, MSAA Senior Writer
Reviewed by Jack Burks, MD, MSAA Chief Medical Officer