Ocrelizumab Noninferior to Fingolimod in Pediatric Relapsing-Remitting MS

Ocrelizumab demonstrates efficacy and safety comparable to fingolimod in children and adolescents with relapsing-remitting multiple sclerosis (MS), according to study results from the phase 3 OPERETTA 2 trial presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress 2025, held in Barcelona, Spain from September 24 to 26, 2025.

Preventing relapses and long-term neurological impairment is a key therapeutic goal for pediatric-onset multiple sclerosis (POMS), yet effective disease-modifying therapies (DMTs) for this population remain limited. Ocrelizumab previously demonstrated favorable tolerability and relapse prevention in patients aged 10 to 17 years in OPERETTA 1 (ClinicalTrials.gov Identifier: NCT04075266), supporting further investigation.

OPERETTA 2 (ClinicalTrials.gov Identifier: NCT05123703) is a phase 3, randomized, double-blind, double-dummy, multicenter, parallel-group, noninferiority trial designed to compare the safety and efficacy of intravenous ocrelizumab with oral fingolimod in pediatric relapsing-remitting MS.

Patients with POMS received either ocrelizumab 600 mg every 24 weeks or fingolimod 0.5 mg daily, with matching placebos. The primary endpoint was noninferiority of ocrelizumab vs fingolimod based on annualized relapse rate. Secondary endpoints included the number of new or enlarging T2 lesions and gadolinium-enhancing T1 lesions at week 12, with safety assessed by the incidence and severity of adverse events.

A total of 187 patients aged 10 to 17 years were included, of whom 69.0% were women and the median age (range) was 15.0 (11-17) years. At baseline, patients had a median (range) of 43 (2-237) T2 lesions and 0.5 (0-28) gadolinium-enhancing T1 lesions. A total of 47.1% presented with gadolinium-enhancing T1 lesions. The median (range) Expanded Disability Status Scale score was 1.5 (0-5.5).

Ocrelizumab met the primary endpoint, showing noninferiority to fingolimod in controlling relapses (rate ratio, 0.52; 95% CI, 0.19-1.33). By week 24, ocrelizumab led to a near complete suppression of relapses. Relapses in the ocrelizumab cohort were moderate and resolved fully, whereas in the fingolimod cohort, they ranged from mild to severe, with 12.5% of patients not fully recovered at the last assessment.

Ocrelizumab also met secondary endpoints. It reduced the number of new or enlarging T2 lesions by 48% (rate ratio, 0.52; 95% CI, 0.36–0.76; P =.001) and reduced gadolinium-enhancing T1 lesions at week 12 by 87% (rate ratio, 0.13; 95% CI, 0.03-0.41; P =.001).

“Ocrelizumab-treated patients had far fewer new T lesions, and markedly fewer new enhancing lesions, indicating that ocrelizumab is superior as a treatment in terms of suppression of MRI evidence of new disease activity,” said Brenda Banwell, MD,  Director of Johns Hopkins Medicine Department of Pediatrics, in an interview with Neurology Advisor.

Adverse events were slightly more common with ocrelizumab than with fingolimod (89.2% vs 78.3%), mainly due to infusion-related reactions and respiratory tract infections. Though Dr Banwell noted, “[w]hile pediatric MS patients treated with ocrelizumab had more infections compared to the patients treated with fingolimod, infections were generally mild and no patient stopped treatment with ocrelizumab due to recurrent or severe infection.”

“If approved, ocrelizumab has the potential to be a highly effective and well tolerated treatment for POMS, with an already well-established safety profile in adults,” study authors concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.