Ocrelizumab established as a new option for children with MS

The phase 3 OPERETTA 2 trial demonstrated the safety and efficacy of ocrelizumab as a new treatment option for paediatric-onset multiple sclerosis (POMS). Compared with fingolimod, ocrelizumab was associated with a risk reduction (RR) of almost 50% in annualised relapse rate (ARR). Safety outcomes were comparable between treatments.

Approved treatment options for POMS remain limited, especially among high-efficacy disease-modifying treatments (DMTs). In the phase 2 OPERETTA 1 trial (NCT04075266), ocrelizumab was well tolerated in MS patients aged 10-17 years [1]. Based on these results, the phase 3, randomised, double-blind, non-inferiority OPERETTA 2 study (NCT05123703) was designed to compare ocrelizumab with fingolimod in 10 to 17-year-olds with POMS.

Prof. Brenda Banwell (Johns Hopkins University, MD, USA) presented the primary analysis [2]. Participants were randomised 1:1 to receive either ocrelizumab 600 mg intravenously every 24 weeks or oral fingolimod 0.5 mg daily, with matching placebos, until the last randomised participant had completed ≥24 weeks. Participants could then enter the ongoing open-label extension with ocrelizumab for ≥144 weeks. The primary endpoint was the non-inferiority of ocrelizumab compared to fingolimod in ARR.

Of the 187 participants randomised, 129 (69.0%) were female. Median baseline age was 15 years, and median baseline EDSS was 1.5 (range 0.0-5.5). Median treatment duration during the double-blind phase was approximately 75 weeks in both groups.

Ocrelizumab was non-inferior to fingolimod in controlling relapses and was associated with a 48% RR in ARR (relapse rate ratio 0.52; 95% CI 0.19-1.33). Dr Banwell added that relapses were nearly suppressed from week 24 onwards. Ocrelizumab also significantly reduced the number of new or enlarging T2 lesions compared with fingolimod, with a 48% relative risk reduction (RR 0.52; 95% CI 0.36-0.76; P=0.001). The risk of T1 gadolinium-enhancing lesions was reduced by 87% (RR 0.13; 95% CI 0.02-0.41).

Adverse events (AEs) were reported ‘slightly more’ frequently in the ocrelizumab group. Serious AEs and infections were rare and balanced between groups, and no serious AEs led to ocrelizumab discontinuation.

1. Waubant E, et al. Ocrelizumab dose selection for treatment of paediatric relapsing-remitting multiple sclerosis: long-term 96-week safety and efficacy results of the Phase II OPERETTA 1 study. O106, ECTRIMS 2025, 24-26 September 2025, Barcelona, Spain.
2. Benwell B, et al. Efficacy and safety of ocrelizumab compared with fingolimod in paediatric relapsing-remitting MS: results of the Phase III OPERETTA 2 study. O130, ECTRIMS 2025 Congress, 24-26 September 2025, Barcelona, Spain.

Medical writing support was provided by Michiel Tent.

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Posted on 29 September 202529 September 2025