Ocrelizumab Shows Similar Efficacy to Fingolimod in Phase 3 OPERETTA 2 Trial for Pediatric Relapsing-Remitting MS

New late breaking data presented at the 2025 European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) Congress, held September 24-26, in Barcelona, Spain, of the phase 3 OPERETTA 2 study (NCT05123703) revealed that intravenous ocrelizumab (Ocrevus; Genentech) was noninferior to fingolimod (Gilenya; Novartis) in terms of efficacy for controlling relapses in patients with pediatric-onset relapsing-remitting multiple sclerosis (RRMS).¹ The trial continues on, as patients are transitioning to the open-label extension phase, where they receive ocrelizumab treatment for at least 144 weeks.

Among 187 pediatric patients (ocrelizumab, n = 93; fingolimod, n = 94), ocrelizumab was noninferior to fingolimod for annualized relapse rate, with a risk reduction of 48% (rate ratio, 0.52; 95% CI, 0.19-1.33). Findings also showed that ocrelizumab led to near complete suppression of relapses at 24 weeks. Notably, ocrelizumab was superior to fingolimod on MRI end points, resulting in 48% fewer new or enlarging T2 lesions during the trial (rate ratio, 0.52; 95% CI, 0.36-0.76; P = .001) and 87% fewer T1 gadolinium-enhancing (Gd+) lesions at 12 weeks (rate ratio, 0.13; 95% CI, 0.03-0.41; P = .001).

“Children aged [at least] 18 years who develop MS are diagnosed with [pediatric-onset] MS (POMS), an often highly active disease that accounts for 3%-5% of all MS cases worldwide. Preventing disease activity, relapses and the accrual of irreversible neurological impairment is a key goal of MS therapy, particularly in POMS. The ultimate therapeutic goal is to achieve complete remission of clinical and MRI activity without tolerability or safety issues,” lead author Brenda Banwell, MD, pediatrician-in-chief and co-director at Johns Hopkins Children’s Center, and colleagues wrote.¹ “More [disease-modifying therapies] options are required for POMS. 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.”

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OPERETTA 2 is a phase 3, randomized, double-blind, double-dummy, parallel-group, multicenter study investigating the efficacy and safety of IV ocrelizumab versus fingolimod in patients aged between 10 and 17 years with pediatric-onset RRMS. Researchers randomized participants 1:1 to receive either 600-mg ocrelizumab IV every 24 weeks or daily oral 0.5 mg fingolimod, with matching placebos, during a double-blind period that continued until all patients completed 24 weeks. The primary objective was to demonstrate noninferiority of ocrelizumab compared with fingolimod in annualized relapse rate, whereas secondary objectives included the number of new or enlarging T2 lesions and T1 Gd+ lesions at 12 weeks.

Within the study cohort, 129 of the participants were women (69.0%). The median age at baseline was 15.0 years (range, 11-17) and the median body weight was 63.1 kg (range, 42.3-154.2). At baseline, patients had a median of 43 T2 lesions (range, 2-237) and 0.5 T1 gadolinium-enhancing lesions (range, 0-28), with 88 participants (47.1%) presenting at least 1 T1 Gd+ lesion. Additionally, researchers reported that the median baseline Expanded Disability Status Scale score was 1.5 (range, 0-5.5). Results from the current study build on prior findings from the phase 1 OPERETTA 1 study (NCT04075266), in which ocrelizumab prevented relapses in pediatric patients over 96 weeks and was well tolerated.²

Adverse events (AEs) in the ocrelizumab arm (n = 82) were primarily driven by infusion-related reactions and respiratory tract infections, most of which were nonserious. No AEs led to treatment withdrawal in the ocrelizumab arm, and few serious AEs were observed (n = 6). Infusion-related reactions occurred more frequently in the ocrelizumab arm (n = 45) than in the fingolimod arm (n = 22). Additionally, 24% of patients in the fingolimod arm who received placebo infusions experienced infusion-related reactions. In the ocrelizumab arm, 93.3% of infusion-related reactions (n = 42) were mild or moderate, and 6.7% (n = 3) were severe; all resolved and none resulted in treatment discontinuation. More patients in the ocrelizumab arm experienced infections, although serious infections were infrequent in both treatment arms.

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REFERENCES
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.
2. Schreiner T, Mar S, Valeriani M, et al. Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: pharmacokinetic, safety, and efficacy results from OPERETTA 1. Presented at: 2024 CMSC Annual Meeting; May 29-June 2; Nashville, TN. ABSTRACT DMT02.