Overviewing Phase 3 OPERETTA 2 Trial and Ocrelizumab’s Impact on Pediatric Multiple Sclerosis: Brenda Banwell, MD, FRCPC, FAAN

WATCH TIME: 4 minutes

"This trial marks a major step forward for children with multiple sclerosis. Ocrelizumab not only met its primary and secondary endpoints but showed a strong safety and efficacy profile comparable to adults, giving us a new high-efficacy option for this underserved population."

Ocrelizumab (Ocrevus; Genentech) is a humanized monoclonal antibody that is FDA-approved for the treatment of adult patients with relapsing forms of multiple sclerosis (MS) and primary progressive MS. To date, it remains the only approved therapy for progressive forms of the disease, a subtype that continues to show degeneration even as relapses become controlled.

At the 2025 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 24-26, in Barcelona, Spain, investigators presented promising data from OPERETTA 2, a phase 3 trial (NCT05123703) testing the safety and efficacy of intravenous (IV) ocrelizumab in pediatric patients aged 10-17 years with relapsing-remitting MS. The study, a double-blind, double-dummy, non-inferiority trial, is a follow up to OPERETTA 1 (NCT04075266), and evaluates ocrelizumab’s impact against fingolimod (Gilenya; Novartis), the only FDA-approved treatment for pediatric onset MS.

In the trial, 187 patients with pediatric-onset MS received either 600 mg ocrelizumab IV every 24 weeks or daily oral 0.5 fingolimod, with matching placebos, over a double-blind period that lasted until the last randomized patient completed 24 weeks. The primary objective was to demonstrate noninferiority of ocrelizumab versus fingolimod based on annualized relapse rate, with secondary objectives assessing new or enlarging T2 lesions during the double-blind period and T1 gadolinium-enhancing lesions at week 12.

Following the meeting, NeurologyLive® sat down with study author Brenda Banwell, MD, FRCPC, FAAN, to provide an overview of the study’s findings and their significance. Banwell, who serves as pediatrician-in-chief at Johns Hopkins Children’s Center, outlined the key data presented at the meeting, including the treatment’s consistent safety profile, with no unexpected adverse events or treatment withdrawals in the ocrelizumab. Of note, she discussed how these results support regulatory submissions that could expand therapeutic options for pediatric MS, an area with limited approved treatments.

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REFERENCE
1. Banwell B, Kotulska-Jozwiak K, Rostásy K, et al. Efficacy and safety of ocrelizumab compared with fingolimod in paediatric relapsing-remitting MS: results of the Phase III OPERETTA 2 study. Presented at ECTRIMS Congress; September 24-26, 2025; Barcelona, Spain. Late-Breaking Abstract O130.