Ocrelizumab Delays Disability Progression in Primary Progressive Multiple Sclerosis


Those treated with ocrelizumab observed a 46% reduction in their risk of progressing to a wheelchair compared to those administered placebo treatments.

Helmut Butzkueven, MBBS, PhD

A new analysis of the ONTARIO study has shown that ocrelizumab (Ocrevus, Genentech) can aid in the delaying of disability progression in patients with primary progressive multiple sclerosis (PPMS).

The exploratory analysis of the phase III trial’s extended control period revealed that the use of ocrelizumab could significantly delay the need for a wheelchair by 7 years, as measured by Expanded Disability Status Scale (EDSS) scores of ≥7 using 24-week confirmed disability progression (CDP). The new data will be presented at the 4th Congress of the European Academy of Neurology (EAN) in Lisbon, Portugal.

Those treated with ocrelizumab observed a 46% reduction in their risk of progressing to a wheelchair compared to those administered placebo (6.2% vs. 9.8%; P = .022). When extended to calculate patients’ median time-to-wheelchair, a 7-year difference was observed—19.2 years for those in the intervention group compared with 12.1 years for those given placebo.

When comparing the data to an untreated real-world PPMS population, the analysis revealed that the placebo-treated control group in ONTARIO had a similar rate of disability progression. The control group’s EDDS ≥7 of 12.1 years was comparable to 12.4 years for those with PPMS in the real world MSBase registry.

“To a person living with primary progressive MS, for whom disability accumulates twice as fast as in relapsing MS, 7 more years without the need for a wheelchair could extend the time they can live independently in their home, continue working or looking after their families,” said Helmut Butzkueven, MBBS, PhD, a professor and Chair of MS and Neuroimmunology Research at Central Clinical School, Monash University.1

Long-term safety data representing 3778 patients with relapsing multiple sclerosis (RMS) and PPMS, and 9474 patient-years of exposure to ocrelizumab remained consistent with a favorable risk-benefit profile. According to Genentech, more than 50,000 patients have been treated with the therapy as of June 2018.

“The data at EAN show the significant impact that OCREVUS, the first disease-modifying medicine for PPMS approved in more than 60 countries around the world, can have on people with MS with the greatest unmet need,” Butzkueven, also the head of MS and Neuroimmunology Service at Alfred Health and Director of MS Service at Eastern Health, added.

The ONTARIO data revealing that 32.9% of patients treated with ocrelizumab had 12-week CDP compared to 39.2% with placebo (hazard ratio [HR], 0.76; 95% CI, 0.59 to 0.98; P = .03).2 The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (HR, 0.75; 95% CI, 0.58 to 0.98; P = .04).

Additionally, the performance on the timed 25-foot walk worsened by 38.9% for those administered ocrelizumab by week 120, compared to 55.1% for those given placebo (P = .04). Ocrelizumab decreased the total volume of brain lesions on T2-weighted magnetic resonance imaging (MRI) by 3.4%, while it increased by 7.4% with placebo (P <.001). Brain-volume loss was 0.90% with ocrelizumab compared to 1.09% with placebo (P = .02).

In 2017, the therapy was the first of its kind approved by the US Food and Drug Administration (FDA) for the treatment of PPMS.


1. Genentech Announces New Ocrevus (Ocrelizumab) Data on Long-Term Disability Benefits in Primary Progressive Multiple Sclerosis and Initiation of two Global Studies in Progressive MS [press release]. San Francisco, CA: Genentech; June 13, 2018. gene.com/media/press-releases/14730/2018-06-13/genentech-announces-new-ocrevus-ocrelizu. Accessed June 14, 2018.

2. Montalban X, Hauser SL, Kappos L, et. al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. New Engl J Med. 2017;376:209-220.


: 10.1056/NEJMoa1606468.

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