Ocrelizumab appears to reduce clinical and MRI disease activity compared to placebo in patients with primary progressive multiple sclerosis (PPMS), for which there is currently no approved treatment.
Results from the ORATORIO trial were presented at the 2016 CMSC Annual Meeting in National Harbor, MD.
The new drug has previously shown promise as a treatment for relapsing-remitting MS, in which it promoted measures of no evidence of disease activity (NEDA) in the OPERA I and OPERA II phase 3 trials. Being that ocrelizumab is a humanized monoclonal antibody that selectively targets CD20+ B cells, investigators led by Jerry Wolinsky, MD, of the University of Texas Health Science Center in Houston, evaluated the efficacy of ocrelizumab in patients with PPMS with an without T1 gadolinium-enhancing (Gd+) lesions at baseline.
The Phase 3, randomized, double-blind, placebo-controlled ORATORIO trial included 732 patients who were randomized to receive either 600mg of ocrelizumab intravenous infusions as 2 300mg infusions 14 days apart or placebo every 24 weeks for at least 120 weeks until a specified number of 12-week confirmed disability progression (CDP) events occurred. The primary endpoint was time to onset of 12-week confirmed disability progression.
Compared to placebo, ocrelizumab significantly reduced the risk of 12-week CDP by 24% (hazard ratio [HR] = 0.76; P= .0321), 24-week CDP by 25% (HR = 0.75; P= .0365), and T2 lesion volume (−3.4% with OCR vs +7.4% with PBO [P< .0001]). T1 Gd+ lesions were present at baseline in 27.5% of patients treated with ocrelizumab vs 24.7% of patients treated with placebo. In patients with and without T1 Gd+ lesions at baseline, respectively, ocrelizumab reduced the risk of 12-week CDP by 35% (HR = 0.65 [95% CI, 0.40-1.06]; P= .0826) and 16% (HR = 0.84 [95% CI, 0.62-1.13]; P= .2441); risk of 24-week CDP by 33% (HR = 0.67 [95% CI, 0.40-1.14]; P= .1417) and 19% (HR = 0.81 [95% CI, 0.59-1.10]; P= .1783); and total T2 lesion volume by −3.8% (95% CI, −7.0 to −0.5) with ocrelizumab vs 12% (95% CI, 7.2-17.1) with placebo (P< .001) and −3.1% (95% CI, −5.0 to −1.1) with ocrelizumab vs 6.1% (95% CI, 3.3-9.0) with placebo (P< .001).
Overall, the results indicate that ocrelizumab may be a promising treatment option in patients with PPMS.
Please see abstract for full disclosures.
Wolinsky J, Arnold DL, Bar-Or A, et al. Abstract DX06. Ocrelizumab Efficacy in Primary Progressive Multiple Sclerosis Patients in the Presence/Absence of T1 Gadolinium-Enhancing Lesions at Baseline in a Phase 3, Placebo-Controlled Trial. Presented at: 2016 CMSC Annual Meeting. June 1-4, 2016; National Harbor, MD.