Introduction B cells are implicated in MS pathophysiology, including primary progressive MS (PPMS). Ocrelizumab (OCR) is a humanised monoclonal antibody that selectively targets CD20+ B cells. OCR was evaluated in PPMS in a Phase III, randomised, double-blind, placebo-controlled study (ORATORIO; NCT01194570).
Methods Eligible PPMS patients were randomised 2:1 to receive OCR 600 mg or placebo every 24 weeks for ≥120 weeks, until a pre-specified number of 12-week confirmed disability progression (CDP) events occurred. The primary endpoint was time-to-onset of 12-week CDP. Secondary endpoints included: time-to-onset of ≥24-week CDP; changes in timed 25-foot walk (T25-FW), total T2 lesion volume at 120 weeks and total brain volume between 24 and 120 weeks; and safety.
Results Compared with placebo, OCR significantly reduced: risk of 12- (24%; p=0.0321) and 24-week CDP (25%; p=0.0365); T25FW progression rate (29% [OCR: +39%; placebo: +55%; p=0.0404]); T2 lesion volume (OCR: –3.4%; placebo: +7.4%; p<0.0001); and brain volume loss rate (17.5% [OCR: –0.9%; placebo: –1.1%; p=0.0206]). Adverse events (AEs) and serious AEs were balanced between groups.
Conclusions OCR is the first investigational therapy to meet key efficacy outcomes with a favourable safety profile in a Phase III PPMS study.
Sponsored by F. Hoffmann-La Roche Ltd.