Efficacy and Safety of Ocrelizumab Compared With Fingolimod in Pediatric-onset Relapsing-remitting MS: Results of the Phase III OPERETTA Two Study
Brenda Banwell1, Katarzyna Kotulska2, Kevin Rostásy3, Kumaran Deiva4, Henry Sato5, Massimo Filippi6, Tanuja Chitnis7, Maria Pia Sormani8, Lauren Krupp9, Amit Bar-Or10, Joanna Evershed11, Bouchra El Azzouzi12, Qing Wang12, Chien-Ju Lin11, Alexandra Hogea11, Hans-Martin Schneble12, Corinne Manlius12, Emmanuelle Waubant13
1Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA, 2Department of Neurology and Epileptology, The Children’s Memorial Health Institute, Warsaw, Poland, 3Pediatric Neurology at Children's Hospital, Datteln, Germany, 4Department of Pediatrics Neurology, Bicêtre Hospital, Le Kremlin-Bicêtre, France and Paris Sud-Saclay University, Le Kremlin-Bicêtre, France, 5Neurological Institute of Curitiba, Curitiba, PR, Brazil, 6Neuroimaging Research Unit, Division of Neuroscience, Neurology Unit, Neurorehabilitation Unit and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, and Vita-Salute San Raffaele University, Milan, Italy, 7Department of Pediatric Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA and Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, 8DISSAL, University of Genoa, Genoa, Italy, 9Department of Neurology, NYU Langone Health, New York, NY, USA, 10Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, 11Roche Products Ltd, Welwyn Garden City, UK, 12F. Hoffmann-La Roche Ltd, Basel, Switzerland, 13Neurology, University of California San Francisco, San Francisco, CA, USA
Objective:
OPERETTA 2 (NCT05123703), a Phase III, randomized, noninferiority study, evaluated the safety and efficacy of intravenous (IV) ocrelizumab compared with fingolimod in patients with pediatric-onset multiple sclerosis (POMS) aged 10-17 years.
Background:
POMS is characterized by frequent relapses and rapid accrual of magnetic resonance imaging (MRI) lesions. Treatment options for POMS are limited worldwide, especially high-efficacy disease-modifying therapies. In OPERETTA 1 (NCT04075266), ocrelizumab was well tolerated and prevented relapses in patients with POMS treated ≥96 weeks.
Design/Methods:
Patients were randomized (1:1) to ocrelizumab IV 600 mg every 24 weeks or oral fingolimod 0.5 mg daily, with matching placebos, over a double-blind period (DBP) until all patients completed ≥24 weeks. The primary objective was to demonstrate that ocrelizumab was noninferior to fingolimod based on annualized relapse rate. Secondary endpoints were numbers of new/enlarging T2 lesions during the DBP and T1 gadolinium-enhancing (Gd+) lesions at Week 12. Safety was also monitored.
Results:
Of 187 patients randomized, 129 (69.0%) were female. At baseline, median (range) age was 15.0 (11-17) years and body weight was 63.1 (42.3-154.2) kg. 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. Ocrelizumab was noninferior to fingolimod in controlling relapses (rate ratio [RR], 0.52; 95% CI 0.19-1.33) and superior in reducing the rate of new/enlarging T2 lesions in the DBP (RR, 0.52; 95% CI 0.36-0.76; P=0.001) and T1 Gd+ lesions at Week 12 (RR, 0.13; 95% CI 0.03-0.41; P=0.001). Ocrelizumab was well tolerated; most infusion-related reactions were mild or moderate and occurred in 48.4% of patients. No adverse events led to ocrelizumab treatment withdrawal.
Conclusions:
Ocrelizumab was noninferior to fingolimod on relapse activity and superior on MRI endpoints, and the safety profile was consistent with studies in adults, making ocrelizumab a potential high‑efficacy treatment option for POMS.
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