Rethinking Progressive MS Studies to Better Include Advanced Patients: Gavin Giovannoni, MBBCh, PhD, FCP, FRCP, FRCPath

WATCH TIME: 4 minutes | Captions are auto-generated and may contain errors.

"ORATORIO-HAND changes how we design progressive MS trials—event-driven, composite end points, and more inclusive of advanced patients who’ve too often been left out of research."

There were several notable late-breaking presentations at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2025 Congress, including findings from the phase 3b ORATORIO-HAND trial (NCT04035005) of ocrelizumab (Ocrevus; Genentech). Led by Gavin Giovannoni, MBBCh, PhD, FCP, FRCP, FRCPath, the trial comprised a wide range of patients with primary progressive multiple sclerosis, including those with more advanced MS, defined as Expanded Disability Status Scale (EDSS) scores of 7.0 to 8.0.

All told, ocrelizumab met its primary end point, with 32.7% of patients experiencing confirmed disability progression at 12 weeks compared with 40.4% of those on placebo (HR, 0.70; 95% CI, 0.57-0.86; RR, 30%; P = .0007). In addition, 16.7% of ocrelizumab-treated patients had confirmed progression in hand function on the 9-Hole Peg Test (RR, 41%; P = .0002), an end point Giovannoni believes should be used more frequently. Above all, the ORATORIO-HAND trial confirmed findings from the previously completed ORATORIO study (NCT01194570), and provided new evidence of benefit in an older, more disabled patient population.

Giovannoni, a professor of neurology at Barts and The London School of Medicine and Dentistry, sat down with NeurologyLive® to discuss the key lessons from ORATORIO-HAND and their implications for future MS trial design. He explained how the trial, which uniquely enrolled patients with advanced primary progressive MS, introduced an event-driven model and emphasized upper-limb function—measured by the 9-Hole Peg Test—over traditional EDSS end points that are less sensitive in late-stage disease. Giovannoni noted that this approach allows for smaller, shorter, and more ethically efficient trials while including patients who have historically been excluded due to high disability scores.

Click here for more ECTRIMS 2025 coverage.

REFERENCE
1. 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 Congress; September 24-26, 2025; Barcelona, Spain. Late-Breaking Abstract O128.