Ocrelizumab

Ocrelizumab (trade name Ocrevus) is a humanized anti-CD20 monoclonal antibody. It targets CD20 marker on B lymphocytes and hence is an immunosuppressive drug. Ocrelizumab binds to an epitope that overlaps with the epitope to which rituximab binds. Ocrelizumab (trade name Ocrevus) is a humanized anti-CD20 monoclonal antibody. It targets CD20 marker on B lymphocytes and hence is an immunosuppressive drug. Ocrelizumab binds to an epitope that overlaps with the epitope to which rituximab binds. It was approved by the FDA in March 2017 as a treatment for multiple sclerosis, and the first FDA approved drug for the primary progressive form of MS; it was discovered and developed and is marketed by Hoffmann–La Roche's subsidiary Genentech under the trade name Ocrevus. With the approval, the FDA also required the company to conduct several Phase IV clinical trials to better understand whether the drug is safe and effective in young people, cancer risks, and effects on pregnant women and children they might bear. At launch, the drug was priced at $65,000 (annual cost, for two infusions per year). Ocrelizumab is used to treat relapsing or primary progressive forms of multiple sclerosis. It is administered by intravenous infusion. Ocrelizumab should not be used in people with hepatitis B infection or a history of severe reaction to this drug. If someone has an infection or infectious disease, treatment should be delayed until the infection is resolved. It has not been tested in pregnant women, but based on animal studies does not appear to be safe for pregnant women to take; it is excreted in breast milk, and effects on infants are unknown. As of October 2016 the three Phase III clinical trials of ocrelizumab used to obtain approval had not been published. Based on published data from clinical trials at that time, the most common adverse events were infusion reactions including itchy skin, rash, hives, flushing, throat and mouth irritation, fever, fatigue, nausea, rapid heart beating, headache, and dizziness. One person died from a systemic inflammatory response syndrome and in another trial, rates of cancer were three times higher (2.3% vs 0.8%) in people taking the drug than people taking placebo. Clinical trials in rheumatoid arthritis and lupus were halted because rates of serious infections were too high; these results were not seen in published trials in people with MS, and the differences may be due to the differences in the bodies of people with the different diseases, as well as other drugs they were taking. There is an increased risk of infections of all kinds, including respiratory infections, in people taking immunosupressive drugs like ocrelizumab; however, in clinical trials submitted to the FDA, more people taking ocrelizumab got infections than people taking Interferon beta-1a did, including upper and lower respiratory infections, herpes, and hepatitis B reactivation; the risk of progressive multifocal leukoencephalopathy, a disease caused by viral infection of the brain, is also increased. An increased risk of malignancy with ocrelizumab may exist. In controlled trials, malignancies, including breastcancer, occurred more frequently in ocrelizumab-treated patients. Breast cancer occurred in 6 of 781 females treated with ocrelizumab for MS in clinical trials. None of 668 females treated in Rebif (interferon beta-1a) or placebo arms of the clinical trials developed breast cancer. Patients should follow standard breast cancer screening guidelines. Ocrelizumab is an immunosuppresive drug; it binds to CD20, which is selectively made by B cells, and when ocrelizumab binds to CD20 it kills B cells by causing antibody-dependent cell-mediated cytotoxicity and, to a lesser extent, complement-dependent cytotoxicity.