On May 27, 2016 the Food and Drug Administration (FDA) approved daclizumab (Zinbryta®) for the treatment of adults with relapsing forms of multiple sclerosis (MS). The product, which targets interleukin-2 receptor alpha chain (CD25), is manufactured using a high-yield process. Daclizumab (Zenapax®) was first approved in 1997 for the prevention of organ transplant rejection. While the two products have the same amino acid sequence, Zinbryta has a different glycosylation pattern and reduced antibody-dependent cytotoxicity compared to Zenapax. Zinbryta’s approval was based in part on the results of the Phase 3 DECIDE study (NCT01064401) of Zinbryta versus interferon β 1a (Avonex®) in patients with relapsing-remitting MS. In this study, patients administered Zinbryta experienced fewer clinical relapses than those who received Avonex (annualized relapse rate 0.22 vs. 0.39; 45% lower rate with Zinbryta; P<0.001). Due to serious safety risks, FDA has included a boxed warning on the product label, and it is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy.
Another antibody therapeutic, ocrelizumab, has been evaluated in a Phase 3 study of patients with primary progressive multiple sclerosis (PPMS). The antibody targets CD20 on B cells, which are implicated in the inflammatory and neurodegenerative processes of MS. Ocrelizumab was granted FDA’s Breakthrough Therapy Designation for PPMS, which is a debilitating form of MS characterized by steadily worsening symptoms. PPMS patients typically do not experience distinct relapses or periods of remission. Currently, no treatments are approved for treatment of the disease. In the pivotal Phase 3 ORATORIO study, treatment with ocrelizumab significantly reduced disability progression and other markers of disease activity compared with placebo. Ocrelizumab is also undergoing evaluation in Phase 3 studies of patients with relapsing-remitting forms of the disease. Genentech plans to submit a marketing application for ocrelizumab as a treatment for MS in 2016. If an application is submitted to FDA by the end of June and receives a priority review, which is a benefit of the Breakthrough Therapy Designation, then ocrelizumab could be approved for marketing in the US by the end of 2016.