History
A study of rituximab in multiple sclerosis with strong results published in 2008, drove interest in B-cell depletion as a strategy to treat multiple sclerosis and has led to extensive off-label use of rituximab to treat primary and relapsing multiple sclerosis.[8][16] Rituximab is a mouse protein, and is immunogenic in humans, and Genentech and its parent Roche decided to focus on the similar, but humanized mAb that they already had, ocrelizumab, for multiple sclerosis instead.[10]
Clinical trials in people with rheumatoid arthritis and lupus were halted in 2010 because people with these conditions developed too many opportunistic infections when taking ocrelizumab.[8][17] It was also studied in hematological cancer.[18]
In multiple sclerosis, phase II results were announced in October 2010, and in October 2015, Genentech presented interim results of three Phase III clinical trials.[19] In February 2016, the US Food and Drug Administration (FDA) granted breakthrough therapy designation for primary progressive multiple sclerosis.[20]
In March 2017, the FDA approved ocrelizumab for relapsing-remitting and primary-progressive multiple sclerosis. It is the first FDA-approved treatment for the primary progressive form.[21][9] When the FDA approved the drug, it required Roche to conduct several Phase IV clinical trials, including: a two-part study in people between ten and 17 years old with relapsing multiple sclerosis to determine dosing, then safety and efficacy in these people, required to be completed by 2024; a prospective five-year study to better understand the risk of cancer, required to be completed by 2030; a prospective study creating a registry of women with MS exposed to ocrelizumab before and during pregnancy, women with MS not exposed to ocrelizumab, and women without MS, to understand the effect on women and children they might bear, due by 2029; an additional pregnancy outcomes study due by 2024; and an additional non-human primate study on fetal development and outcomes due by 2019.[12]
The efficacy of ocrelizumab for the treatment of relapsing forms of multiple sclerosis was shown in two clinical trials in 1,656 participants treated for 96 weeks.[21] Both studies compared ocrelizumab to another MS drug, Rebif (interferon beta-1a).[21] In both studies, the participants receiving ocrelizumab had reduced relapse rates and reduced worsening of disability compared to Rebif.[21] The trials were conducted in the US, Canada, Europe, Latin America, Africa, and Australia.[22]
In a study of PPMS in 732 participants treated for at least 120 weeks, those receiving ocrelizumab showed a longer time to the worsening of disability compared to placebo.[21][22] The study was conducted in the US, Canada, and Europe.[22]
The application for ocrelizumab was granted breakthrough therapy, fast track, and priority review designations.[21] The FDA granted approval of Ocrevus to Genentech, Inc.[21]
Ocrelizumab was approved for use in the European Union in January 2018.[23] In June 2024, the European Commission granted marketing authorization for the fixed-dose combination ocrelizumab/hyaluronidase to be used for subcutaneous injection.[23][24] The FDA approved the fixed-dose combination ocrelizumab/hyaluronidase as a subcutaneous formulation in September 2024.[25]
