Ocrelizumab: First Global Approval.
Ocrelizumab (Ocrevus™) is a humanised anti-CD20 monoclonal antibody that has been developed by Genentech, Inc. (a subsidiary of Roche) for the treatment of multiple sclerosis (MS). The drug is designed to deplete B cells, which play an important role in the pathogenesis of MS. In March 2017, ocrelizumab was approved in the USA for the treatment of patients with relapsing or primary progressive forms of MS; currently, it is awaiting approval in the EU for the same indications. This article summarizes the milestones in the development of ocrelizumab leading to its first global approval for the treatment of MS.
Figure: Key milestones in the development of Ocrevus in multiple sclerosis
We live in hubristic times. By spending time in an elevated position, we come to think of ourselves as gods among men. Wrongfully, or rightfully we misjudge any attack on this inflated self-perception as mere jealousy. And then comes the downfall, because real life isn’t rad like jazz or sweet like cinnamon, it is painful in the lessons it teaches the wilful, and the stupid…
Ocrelizumab (Ocrevus) is a humanised anti-CD20 monoclonal antibody that targets B cells, developed by Genentech, Inc. (subsidiary of Roche Pharma) and Biogen Idec Pharma. Genentech, however, is responsible for development of Ocrevus in MS taking on 100% of the costs, while Biogen Idec will receive tiered, double digit royalties on US sales that will approximate its current 30% interest in Ocrevus. Development of Ocrevus in rheumatoid arthritis was halted in May 2010, quoting safety reasons:
“In March, Roche and Biogen Idec announced the suspension of treatment in the ocrelizumab RA program. This decision followed a recommendation from the independent ocrelizumab RA & Lupus Data and Safety Monitoring Board (DSMB). The DSMB concluded that the safety risk outweighed the benefits observed in these specific patient populations at that time based on an infection related safety signal which included serious infections, some of which were fatal, and opportunistic infections. Subsequently, the U.S. Food and Drug Administration (FDA) placed the RA studies on clinical hold“.
Results from the pooled analysis of the Phase III programme are open access and available on the internet from Emery et al. 2014 in PlosOne. The authors noted a greater number of serious infections were observed in the high dose group OCR500 + methotrexate (MTX) vs. placebo + MTX. In their own words:
“The conclusion that the two doses of OCR, in combination with MTX tested in the RA clinical trials did not demonstrate a superior benefit-risk profile compared with available treatments led to the termination of the clinical development program of OCR in RA. OCR500+MTX demonstrated clinical benefit by improving signs and symptoms of RA and radiographic outcomes –; however this dose was associated with an increased incidence of SIEs. OCR200+MTX did not show superior efficacy compared with existing therapies, but was safe and well-tolerated. The clinical development of OCR is continuing in multiple sclerosis, for which there remains an unmet need for more effective therapies and background immunosuppressant therapy is not used“.
Eyes wide open…