The FDA has greenlighted ocrelizumab (Ocrevus, Genentech) as the first medication for both relapsing and primary progressive forms of multiple sclerosis (RMS/PPMS). Most MS patients have RMS or PPMS at diagnosis.
Ocrelizumab is a humanized monoclonal antibody designed to selectively target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin and axonal damage. This nerve cell damage can lead to disability in patients with MS. Based on data from preclinical studies, ocrelizumab binds to CD20 cell-surface proteins expressed on certain B cells but not on stem cells or plasma cells, thereby preserving important functions of the immune system.
Ocrelizumab is administered by intravenous (IV) infusion every six months. The first dose is given as two 300-mg infusions administered two weeks apart. Subsequent doses are given as single 600-mg infusions.
The phase 3, global, randomized, double-blind, double-dummy OPERA I and OPERA II trials evaluated the efficacy and safety of ocrelizumab (600 mg administered by IV infusion every six months) compared with that of interferon (IFN) beta-1a (44 mcg administered by subcutaneous injection three times per week) in 1,656 subjects with RMS.
Key data showed:
The ORATORIO trial was a phase 3, global, randomized, double-blind study evaluating the efficacy and safety of ocrelizumab (600 mg administered by IV infusion every six months; given as two 300-mg infusions two weeks apart) compared with placebo in 732 subjects with PPMS. The blinded treatment period continued until all of the subjects had received at least 120 weeks of either ocrelizumab or placebo and until a predefined number of confirmed disability progression (CDP) events was reached.
Key findings included:
The most common adverse events associated with ocrelizumab in all three studies included infusion reactions and upper respiratory-tract infections, which were mostly mild-to- moderate in severity.
The results from all three studies were published in the New England Journal of Medicine.
Source: Genentech; March 28, 2017.