Ocrelizumab Shows MRI Benefits vs Fingolimod in Phase 3 Pediatric-Onset Multiple Sclerosis Study

Intravenousocrelizumab (Ocrevus; Genentech) demonstrated noninferiority to oral fingolimod (Gilenya; Novartis) for controlling relapses and superiority on MRI measures of disease activity in pediatric patients with relapsing-remitting multiple sclerosis (MS), according to findings from the phase 3 OPERETTA 2 study (NCT05123703).¹

Presented at the 2026 Child Neurology Society Annual Meeting (CNS), held October 14-17, in Montreal Canada, the randomized, double-blind study enrolled 187 patients (n = 129; 69% female) aged 10 to 17 years with pediatric-onset MS (POMS). Patients presented with a mean (SD) of 57.4 (47.3) T2 lesions and 2.4 (4.6) T1 Gd+ lesions; 47.1% had T1 Gd+ lesions.

Led by Fabien Bakdache, PharmD, global medical science leader at Roche, investigators found that ocrelizumab was noninferior to fingolimod on the primary end point of annualized relapse rate (rate ratio [RR], 0.52; 95% CI, 0.19-1.33). However, ocrelizumab was associated with a lower rate of new or enlarging T2 lesions than fingolimod during the double-blind period (RR, 0.52; 95% CI, 0.36-0.76; P = .001). Notably, the rate of T1 Gd+ lesions at week 12 was also lower with ocrelizumab (RR, 0.13; 95% CI, 0.03-0.41; P = .001).¹

The safety profile of ocrelizumab was consistent with findings from studies in adults, according to the investigators. Infusion-related reactions occurred in 48.4% of patients receiving ocrelizumab, with most reactions classified as mild or moderate. No adverse events led to treatment withdrawal.

In OPERETTA 2, patients were randomized 1:1 to receive intravenous ocrelizumab at a dose of 600 mg every 24 weeks or oral fingolimod at a dose of 0.5 mg daily. The double-blind period continued until all patients had completed at least 24 weeks of treatment. In addition to annualized relapse rate, secondary end points included the number of new or enlarging T2 lesions during the double-blind period and the number of T1 Gd+ lesions at week 12.

OPRETTA 2 was cited as evidence that led the FDA’s decision to approve intravenous ocrelizumab for the treatment of relapsing-remitting multiple sclerosis (RRMS) in pediatric patients aged 10 years and older who weigh at least 55 pounds. The approval, which happened May 2026, expanded a high-efficacy anti-CD20 therapy into a younger population with often highly active disease.² With the decision, ocrelizumab became an FDA-approved treatment option for pediatric RRMS, a group that accounts for an estimated 3% to 5% of MS cases globally and approximately 5000 to 10,000 children and adolescents in the United States.

The pediatric approval also builds on prior dose-selection and safety work from the phase 1 OPERETTA 1 study (NCT04075266), which evaluated ocrelizumab in pediatric patients with RRMS and informed the dose used in the phase 3 trial.²In that earlier study, ocrelizumab prevented relapses through 96 weeks and was generally well tolerated, providing a bridge between adult data and the confirmatory pediatric study.²

Overall, the findings suggested that ocrelizumab may offer a high-efficacy treatment option for pediatric patients with relapsing-remitting MS, with results favoring the therapy on MRI measures of inflammatory disease activity compared with fingolimod. The findings also support further consideration of ocrelizumab in the pediatric population, although longer-term data will be important for evaluating sustained efficacy and safety.

REFERENCES
1. Bakdache F, Banwell B, Kotulska K, et al. Efficacy and Safety of Ocrelizumab Compared With Fingolimod in Pediatric-Onset Relapsing-Remitting MS: Results of the Phase III OPERETTA 2 Study. Presented at: Child Neurology Society; October 14-17, 2026; Montreal Canada.
2. FDA approves Ocrevus (ocrelizumab) for pediatric relapsing multiple sclerosis. Genetech. News release. Published May 2026. Accessed May 2026. https://www.gene.com/media/press-releases
3. 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. https://ectrims.eu