Ocrelizumab Superior to Placebo for Delaying Disability Progression in MS

Devon Cimino
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Publish Date
ECTRIMS_Barcelona_2025
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Researchers evaluated whether ocrelizumab is safe and effective for delaying disability progression in patients with primary progressive multiple sclerosis.
Time to confirmed disability progression was effectively delayed by ocrelizumab in patients with primary progressive multiple sclerosis, including for those with more advanced disease.

Ocrelizumab appears to effectively delay overall disability progression and worsening upper limb function in patients with primary progressive multiple sclerosis (MS), according to study findings presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress 2025, held in Barcelona, Spain from September 24 to 26, 2025.

The findings come from a multicenter, randomized, double-blind, placebo-controlled, phase 3b trial (ClinicalTrials.gov Identifier: NCT04035005) involving individuals with primary progressive MS, including those with advanced disease. Study patients were aged 65 years and younger, and had Expanded Disability Status Scale (EDSS) scores of 3.0 to 3.8. During the trial, researchers randomly assigned patients 1:1 to receive either ocrelizumab 600 mg or placebo every 6 months for up to 144 weeks. Treatment was discontinued early in patients who experienced 340 or more progression events.

The primary endpoint was a composite of time to onset of 12-week confirmed disability progression (≥20% worsening from baseline), which was evaluated via 9-Hole Peg Testing (9HPT) and EDSS scores.

Among patients in the intervention (n=505) and placebo (n=508) groups, the median ages were 48 (range, 18-66) and 47 (range, 22-66) years, the median EDSS scores were 6 (range, 3-8) and 6 (range, 2.5-8.0), and the median treatment duration was 143.7 and 143.4 weeks, respectively.

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The AE profile was balanced between both arms, aligning with the known OCR safety profile.

Overall, the percentage of patients who met the primary composite endpoint was lower in patients who received ocrelizumab vs placebo (32.7% vs 40.4%; hazard ratio [HR], 0.70; 95% CI, 0.57-0.86; risk reduction [RR], 30%; P =.0007). The superiority of ocrelizumab over placebo was demonstrated in both 9HPT results (RR, 41%; P =.0002) and EDSS scores (RR, 33%; P =.0013).

Further analysis among a subset of patients with baseline magnetic resonance imaging activity also revealed lower rates of 12-week confirmed disability progression in ocrelizumab vs placebo recipients (26.8% vs 45.9%; HR, 0.45; 95% CI, 031-0.64; RR, 55%; P <.0001). Ocrelizumab was associated with similar outcomes when assessed via 9HPT (RR, 62%) and EDSS scores (RR, 59%).

The researchers observed similar safety profiles between patients who received ocrelizumab vs placebo, including for the occurrence of any adverse event (AE; 74.9% vs 71.1%), severe AEs (12.8% vs 13.2%), malignancy (1.0% vs 0.6%), infection (48.4% vs 44.7%), and serious infection (6.3% vs 5.3%). However, patients in the ocrelizumab group more commonly reported infusion-related reactions (20.8% vs 4.3%).

According to the researchers, “The AE profile was balanced between both arms, aligning with the known OCR [ocrelizumab] safety profile.”

Disclosures: This study was supported by F. Hoffmann-La Roche Ltd., and multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References:

 Giovannoni G, Airas L, Bove R, et al. Ocrelizumab vs placebo in primary progressive MS: efficacy and safety results of the phase IIIb ORATORIO-HAND study. Presented at: ECTRIMS 2025; September 24-26; Barcelona, Spain. Abstract O128.