FDA Approves First Drug to Treat Two Forms of MS

On March 28, 2017, the United States Food and Drug Administration (FDA) announced the approval of Ocrevus™ (ocrelizumab) for the treatment of two types of multiple sclerosis (MS): relapsing forms of MS (RMS) and primary-progressive MS (PPMS). This is the first time that a medication for MS has been approved for two types of the disease, and the first time that any medication has been approved to treat PPMS. This is very exciting news for the MS community.

Prior to this approval, 14 disease-modifying therapies were available for the treatment of relapsing forms of MS, but no treatments had been approved by the FDA for PPMS. As noted, the approval is for relapsing forms of MS (RMS), which are characterized by sudden flare-ups and remissions. RMS includes relapsing-remitting MS (RRMS) as well as secondary-progressive MS (SPMS) with relapses. The approval is also for primary-progressive MS (PPMS), which is a less-common form of the disease and is characterized by a steady accumulation of symptoms.

Medication and Study Information

Developed by Genentech, a member of the Roche group, Ocrevus™ (ocrelizumab) is a humanized monoclonal antibody designed to selectively target CD20-positive B cells. These are a specific type of immune cell that is an important contributor to the MS-disease process. The fact that Ocrevus targets B cells differentiates it from most of the previously approved disease-modifying therapies for MS, which target a different type of immune cell called “T cells.”

In Phase III trials, 600 mgs of Ocrevus were given via intravenous (IV) infusion every six months. For the first dose in the OPERA studies for people with RMS, and throughout the ORATORIO study (not including the extension study) for people with PPMS, the 600-mg dose was divided into two 300-mg doses, given via IV infusion, and separated by two weeks.

Positive results were seen in three Phase III trials with Ocrevus. OPERA I and OPERA II were studies with relapsing forms of MS. Compared to treatment with Rebif® (interferon beta-1a), Ocrevus showed greater efficacy in reducing annualized relapse rates and reducing disability progression that was sustained for time periods of at least three and at least six months. The ORATORIO study was with PPMS and compared treatment with placebo. The trial showed significant reductions in disability progression sustained for time periods of at least three and at least six months. Reductions in other measures of progressive disease were also seen. In all three studies, Ocrevus reduced the burden of MS lesions as shown on magnetic resonance imaging (MRI).

Adverse events in all three of the Phase III studies were similar between those given Ocrevus and those given either Rebif in the RMS studies or the placebo in the PPMS study. Genentech reports that the most common adverse events seen with this medication were mild to moderate infusion-related reactions and infections.

Multiple Sclerosis News Today published an interview with Dr. Peter Chin, principal medical director of Global Neuroscience Development at Genentech, in an online article dated February 28, 2017. In this interview, Dr. Chin explained that while tumors were more common among individuals given Ocrevus versus those in the control groups, the rates of malignancy were still low and remain within the normal rates for the general population. He also notes that no relationship has been established between B-cell suppression and cancer. These types of potential adverse events will continue to be monitored closely to ensure the safety of individuals taking this medication.

As with all disease-modifying therapies, additional side effects may occur with Ocrevus. These include an increase in infections and other possible, but unlikely, adverse events. MSAA will follow-up with additional information as more details become available.

Events Leading to the Approval of Ocrevus™

• In February 2016, the FDA granted “Breakthrough Therapy Designation” for ocrelizumab (for the treatment of PPMS only), which expedited the review process.
• In June 2016, Genentech announced that the Biologics License Application (BLA) for ocrelizumab had been accepted for review by the FDA. In MSAA’s article on this topic, we note that the brand name Ocrevus™ was submitted by Genentech for use with ocrelizumab.
• Also in June 2016, Genentech announced that ocrelizumab would soon be available to eligible individuals with PPMS through an Expanded Access Program (EAP). An EAP enables participants to receive an investigational medication that has not yet been approved by the FDA.
• In December 2016, the FDA extended the review period of Ocrevus for the treatment of RMS and PPMS, allowing more time for the FDA to review data on the manufacturing process of this potential therapy. The extension was not related to any details involving the safety or effectiveness of Ocrevus.
• In December 2016, the results from three Phase III studies of the experimental medication Ocrevus were published in the December 21, 2016 online issue of the New England Journal of Medicine (NEJM). Among others, positive findings included a reduction in annualized relapse rate, a reduction in confirmed disability progression, reductions in gadolinium-enhancing lesions and whole brain-volume loss, as well as an increase in the proportion of patients who showed no evidence of disease activity.

Comment from MSAA’s Chief Medical Consultant

MSAA’s Chief Medical Consultant Dr. Jack Burks explains, “The approval of Ocrevus greatly increases hope for individuals with MS. First, this medication was shown to be even more effective than a very successful FDA-approved interferon treatment, which has helped – and continues to help – many individuals with relapsing forms of the disease. Second, this is the first MS medication to be approved for PPMS, a form of the disease that has been very difficult to treat, with no available treatments until now. And third, this is the first approved disease-modifying therapy to target antibody-producing lymphocytes known as B cells, versus T cells, which is the traditional target of most existing MS medications. Finding new targets that effectively reduce disease activity is vital to our understanding of MS and its treatments.

“This is one of the most exciting times for the MS community. The addition of this new medication to our current group of approved disease-modifying therapies gives a new option for the treatment of MS, particularly for individuals with PPMS as well as others with relapsing MS whose disease activity could not be well-controlled with other therapies. In addition, the approval of Ocrevus and the results of these studies will help guide future MS research into the disease process and the development of other innovative treatment strategies.”

For More Information

Genentech anticipates that Ocrevus will be available to people in the United States within two weeks. For more information about Ocrevus, please call (844) OCREVUS [or (844) 627-3887]. Genentech also plans to offer patient-assistance programs through Genentech Access Solutions. For more information, please call (866) 4ACCESS [or (866) 422-2377] or visit www.Genentech-Access.com.

For additional information on MS 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 Courtney, MSAA Senior Writer

Reviewed by Dr. Jack Burks, MSAA’s Chief Medical Consultant