AAN 2026: Ocrevus treatment slows disability in advanced PPMS

Ocrevus (ocrelizumab) delayed disability progression and worsening hand function among a large group of people with primary progressive multiple sclerosis (PPMS), including those who were older and had more advanced disease.

The data, which come from the Phase 3 ORATORIO-HAND trial (NCT04035005), were presented by Jiwon Oh, MD, a neurologist at the University of Toronto, at the American Academy of Neurology (AAN) 2026 annual meeting, held April 18-22 in Chicago and online. The trial and presentation are sponsored by Ocrevus’ developer Genentech, a Roche company.

“ORATORIO-HAND is helpful, because it confirms the significant effect of [Ocrevus] on disability in PPMS, and it confirms that there is an effect in older patients and in those with more advanced disease,” Oh said in the talk, “ORATORIO-HAND: Results of the Primary Analysis of Ocrelizumab vs Placebo in Primary Progressive Multiple Sclerosis, Including Older Patients and Those With More Advanced Disease.”

Ocrevus, given via infusions into the bloodstream, and its under-the-skin formulation, Ocrevus Zunovo (ocrelizumab and hyaluronidase-ocsq), are the only approved disease-modifying therapies for PPMS.

Their approvals were supported by data from the Phase 3 ORATORIO trial (NCT01194570), which showed that Ocrevus significantly reduced — by 24% — the risk of disability progression, as assessed by the Expanded Disability Status Scale (EDSS). The drug showed an even greater effect on hand function, reducing the risk of decline on the 9-Hole Peg Test (9HPT) by 44%.

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ORATORIO included PPMS patients up to age 55, and with a maximum disability level of 6.5 on the EDSS scale, where aids like canes or crutches are needed to walk.

Due to these inclusion criteria, “currently, we actually do not know clearly the impact of [Ocrevus] in older people with PPMS and in those with more advanced disease, particularly on the worsening of hand function,” Oh said.

Addressing that knowledge gap was the goal of ORATORIO-HAND, which enrolled a broader group of more than 1,000 adults with PPMS, up to age 65. The maximum EDSS score was 8, corresponding to a disability level at which patients usually rely on a wheelchair.

On average, ORATORIO-HAND participants were older, had greater disability, and had been living with MS for longer than people who participated in ORATORIO. The trial “was successful in recruiting an older and more disabled population of people with PPMS,” Oh said.

Participants were randomly assigned to receive Ocrevus or a placebo, with doses administered every six months after two initial doses spaced by 2 weeks. Treatment continued for a median of about 144 weeks (2.7 years).

The main goal was to evaluate the time to 12-week composite confirmed disability progression (12W-cCDP), defined as at least a 20% worsening on the 9HPT or a prespecified EDSS worsening, either sustained for at least three months.

The risk of 12W-cCDP was significantly reduced, by 30%, with Ocrevus relative to the placebo, with sustained progression in at least one of the assessed measures occurring in 32.7% of people on Ocrevus and 40.4% on the placebo.

Ocrevus was also associated with a reduced risk of worsening on each individual test. Fewer people on Ocrevus experienced a confirmed worsening on the 9HPT (16.7% vs. 24.9%), amounting to a 41% lower risk, and on the EDSS (23% vs. 30.8%), amounting to a 33% lower risk.

Oh also presented data showing what he called “generally a consistent reduction in the risk of disability progression across multiple subgroups,” with benefits seen regardless of sex, age, initial disability levels, or MRI disease activity. Ocrevus’ benefits appeared to be accentuated in women, younger participants, people with greater disability levels, and those with MRI disease activity during the screening period.

Overall, “in a very large PPMS population that specifically included older patients and those with more advanced disease, [Ocrevus] was superior to placebo,” with effects that were “consistent across key clinical subgroups,” Oh said.

Side effects were consistent with the treatment’s known safety profile. As expected, infusion-related reactions were more common with the treatment than the placebo, but rates of infections and cancer were similar between the groups.