Acute necrotizing hemorrhagic leukoencephalitis
Acute hemorrhagic leukoencephalitis of Weston Hurst is at the extreme end of the spectrum of demyelinating diseases. It typically follows a viral upper
Mar. 26, 2021
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The history of the development of ocrelizumab starts with rituximab, another monoclonal antibody (MAb) that was developed for the treatment of autoimmune disorders and was approved for the treatment of CD20-positive follicular non-Hodgkin lymphoma in 1994. In a clinical trial in 2008, rituximab was shown to reduce inflammatory brain lesions and relapses for 48 weeks in patients with relapsing-remitting multiple sclerosis (05). This spiked interest in B-lymphocyte depletion as a strategy to treat multiple sclerosis and led to extensive off-label use of rituximab to treat primary and relapsing multiple sclerosis. However, rituximab is a chimeric MAb and is immunogenic in humans, and the manufacturer decided to focus on the similar but fully humanized MAb, ocrelizumab, for multiple sclerosis instead. Ocrelizumab is designed to selectively target CD20-positive B cells, which are key contributors to myelin and axonal damage that can lead to disability in patients with multiple sclerosis. It was granted approval by the U.S. Food and Drug Administration (FDA) in 2017 as the first treatment indicated for both relapsing and primary progressive forms of multiple sclerosis (03). Following approval, the FDA requires the manufacturer to conduct several phase IV clinical trials to assess drug safety and effectiveness in younger patients (10 to 17 years of age) and pregnant women. Other required studies include a prospective 5-year study to better understand the risk of cancer as well as the creation of a registry of women with multiple sclerosis exposed to ocrelizumab before and during pregnancy, which are both required to be completed by 2029.
Prior to approval for multiple sclerosis, ocrelizumab was also tested in clinical trials for rheumatoid arthritis, lupus nephritis, and B-cell malignancies, but its development for systemic lupus erythematosus and neuromyelitis optica was discontinued.
Ocrelizumab has also been approved by the European Medicines Agency. The drug requires administration by intravenous infusion every 6 months. Ocrelizumab has a reported list price of $65,000, which is approximately 25% below that of the high-dose interferon beta 1a. Genentech, the manufacturer, offers patient assistance programs through Genentech Access Solutions for patients who qualify.
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