A Comprehensive Monograph on Ocrelizumab (Ocrevus®, Ocrevus Zunovo®)

I. Executive Summary

Ocrelizumab represents a significant milestone in the therapeutic landscape of multiple sclerosis (MS), a chronic, inflammatory, and neurodegenerative autoimmune disease of the central nervous system.[1] Marketed under the brand names Ocrevus® for intravenous infusion and Ocrevus Zunovo® for subcutaneous injection, ocrelizumab is a first-in-class, B-cell-targeted disease-modifying therapy (DMT) that has fundamentally altered treatment paradigms.[2] As a recombinant humanized anti-CD20 monoclonal antibody, its approval marked a pivotal moment, particularly for patients with primary progressive multiple sclerosis (PPMS), for whom it was the first-ever approved therapy, addressing a long-standing and critical unmet medical need.[5]

The therapeutic efficacy of ocrelizumab stems from its precise mechanism of action: the selective depletion of B-lymphocytes that express the CD20 surface antigen.[1] This targeted immunomodulation has demonstrated superior efficacy in landmark clinical trials. In the OPERA I and OPERA II studies for relapsing forms of MS (RMS), ocrelizumab significantly reduced relapse rates and disability progression compared to an active comparator, interferon beta-1a.[5] Critically, in the ORATORIO trial, it was the first agent to significantly slow the progression of clinical disability in patients with PPMS compared to placebo.[6] The success of ocrelizumab in PPMS was not merely an incremental advance; it provided definitive clinical validation for the central role of B-cells in the pathophysiology of progressive neurodegeneration, an aspect of MS previously thought to be largely independent of the acute inflammatory processes targeted by older therapies. This has catalyzed new avenues of research into the mechanisms of progressive MS.[8]