It was approved by the U.S. Food and Drug Administration (FDA) in March 2017. The European Commission (EC) granted a marketing authorization valid throughout the EU in January 2018. Today, 90 countries across the globe have approved Ocrevus for the treatment of MS, according to Roche.
Notably, it is the first therapy approved by both the FDA and the EC to treat both relapsing forms of MS and, in a true breakthrough, primary progressive multiple sclerosis (PPMS). PPMS had no approved treatments previously in the U.S. or the EU.
How does Ocrevus work?
Ocrevus is an anti-CD20 monoclonal antibody that targets mature B-cells, a type of immune cell. Almost 95% of B-cells have the CD20 protein on their surface once they mature. This is what makes CD20 a potent marker for therapeutic purposes.
Researchers think that these CD20-positive B-cells target axons, or nerve cell extensions, and the myelin sheaths — which surround and protect nerve cells — on healthy axons. That targeting initiates a cascading series of immune reactions that lead to MS and disability.
Studies have shown that Ocrevus binds to B-cells with CD20 markers, but not to stem cells and plasma cells, preserving vital immune functions within the host. Once Ocrevus binds to a B-cell, it likely causes a reaction that leads to the cells bursting.
In addition to B-cells, recent research also has pointed to Ocrevus targeting T-cells in individuals with PPMS. After six months, the study found, patients had a reduction in CD20 expressing activated T-cells that lead to inflammation, as well as a drop in other types of activated T-cells.
Ocrevus in clinical trials
An ongoing randomized, double-blind, multi-center, Phase 3 clinical trial (NCT01194570) is evaluating the efficacy and safety of Ocrevus in 732 patients with PPMS. Participants in this study, called ORATORIO, receive the treatment as infusions of 300 mg into the bloodstream two weeks apart every six months.
Genentech announced favorable results from the trial in February 2016, showing that it met its primary outcome. Ocrevus treatment significantly reduced clinical disease progression by 24% in PPMS patients compared with a placebo. Researchers measured this using the expanded disability status scale (EDSS). The reduction continued for at least 12 weeks (about three months).
Two related Phase 3 studies, OPERA I and II (NCT01247324 and NCT01412333), also are still ongoing, with trial completion expected in December 2023. These trials are testing the efficacy of the treatment in 1,656 patients with relapsing forms of MS.
Early data showed that Ocrevus was superior to interferon beta-1a, a well-established MS therapy, reducing the annualized relapse rate — the primary endpoint of both studies — by nearly 50% over a two-year controlled treatment period. Patients had received Ocrevus as an infusion into the bloodstream at 600 mg every six months. Meanwhile, those who received interferon beta-1a had an injection under the skin (subcutaneous) at 44 mcg three times per week.
According to Genentech, Ocrevus is the first investigational medicine to show such positive results in patients with both PPMS and relapsing forms of MS.
The company submitted data from all three studies to regulatory authorities in mid-2016. This paved the way for the marketing and commercialization of Ocrevus to treat relapsing forms of MS and PPMS. Genentech announced on June 28, 2016, that the FDA accepted the company’s biologics license application for Ocrevus for review. The agency also granted the therapy priority review, accelerating the review process. All those efforts resulted in the FDA’s decision to approve the treatment on March 28, 2017.
Patients who enrolled in the OPERA I and II trials also were able to enroll in an open-label extension study. Data from six years of treatment showed that patients who received Ocrevus had a lower risk of needing walking aids compared with those given interferon beta-1a treatment (4.3% vs. 7.2%). Ocrevus also was shown to slow damage to a part of the brain called the thalamus as compared with interferon beta-1a.
Researchers published an additional analysis from all three trials in March 2020. It found that patients with moderate to severe disability — EDSS scores of 4.0 or higher — had a significant reduction in disability progression.
Data from the ORATORIO study also showed that early and continuous use of Ocrevus can significantly slow disability progression in people with PPMS as well as delay the time until wheelchair reliance.
A new clinical trial (NCT04448977), launched in October 2020, is seeking to investigate the effects of Ocrevus treatment on cognitive fatigue. This is a frequent problem in MS patients, in which they feel exhausted after a period of concentration.
The study will recruit up to 60 adults, ages 16 to 64, who will be enrolled into one of three groups. One will include patients with relapsing-remitting MS (RRMS), who will take Ocrevus. A second group will involve RRMS patients who will take Copaxone, while the final group will be composed of healthy people (controls).
All participants will be monitored for changes in brain activity and fatigue time after completing a mentally demanding exercise called the symbol digit modality task. Assessments also will be made after six months of treatment, and after 12 months. Recruitment has not yet started but will begin at the Kessler Foundation in New Jersey. This study is expected to conclude in July 2022.
Ocrevus is a twice-yearly infusion. In the first year only, it will be given three times, as the initial dose is split into two infusions. Initially, the infusions took 3.5 hours to complete. However, both the FDA and the European Medicines Agency have approved the use of a shorter two-hour infusion.
Side effects include infusion-related reactions, low levels of immunoglobulins, and a higher risk of infection. Ocrevus use also may increase the risk of developing certain types of cancer such as breast cancer.
Last updated: Feb. 17, 2021
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