Abstract Details

Title Efficacy and Safety of Ocrelizumab Compared With Fingolimod in Pediatric-onset Relapsing-remitting MS: Results of the Phase III OPERETTA Two Study

Topic Multiple Sclerosis

Presentation(s) S40 - Multiple Sclerosis: Clinical Trials/Science and Real-world Evidence (1:48 PM-2:00 PM)

Poster/Presentation
Number 005

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.

Authors/Disclosures
Brenda L. Banwell, MD, FAAN (Johns Hopkins University) PRESENTER	Dr. Banwell has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Banwell has received personal compensation in the range of $0-$499 for serving as a Consultant for UCB. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Banwell has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Banwell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Banwell has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Banwell has received research support from National MS Society. The institution of Dr. Banwell has received research support from NIH.
Katarzyna Kotulska-Jozwiak (Centrum Zdrowia Dziecka)	Prof. Kotulska-Jozwiak has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Prof. Kotulska-Jozwiak has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Prof. Kotulska-Jozwiak has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Prof. Kotulska-Jozwiak has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Prof. Kotulska-Jozwiak has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Prof. Kotulska-Jozwiak has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Biogen. Prof. Kotulska-Jozwiak has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Novartis. The institution of Prof. Kotulska-Jozwiak has received research support from Novartis. The institution of Prof. Kotulska-Jozwiak has received research support from Polish Mdical Research Agency. The institution of Prof. Kotulska-Jozwiak has received research support from European Commission. Prof. Kotulska-Jozwiak has a non-compensated relationship as a member with ERN EPICARE that is relevant to AAN interests or activities.
Kevin Rostasy	Kevin Rostasy has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Kevin Rostasy has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck.
Kumaran Deiva	Kumaran Deiva has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Kumaran Deiva has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Kumaran Deiva has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Kumaran Deiva has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Kumaran Deiva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Octagam. Kumaran Deiva has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sqy therapeutics.
Henry Sato, MD (INC)	Henry Sato, MD has nothing to disclose.
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.
Tanuja Chitnis, MD, FAAN (Brigham and Women's Hospital)	Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octave Biosciences. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. The institution of Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. The institution of Dr. Chitnis has received research support from Genentech-Roche. The institution of Dr. Chitnis has received research support from Tiziana Life Sciences. The institution of Dr. Chitnis has received research support from Bristol-Myers Squibb. The institution of Dr. Chitnis has received research support from Wesley Clover.
Maria Pia Sormani (University of Genoa)	Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol meyer. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic. Maria Pia Sormani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis, Roche. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche.
Lauren B. Krupp, MD, FAAN (NYU Langone Medical Center)	Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EBIX. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman LaRoche. Dr. krupp has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MMMK. Dr. krupp has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Patrick, Dolan, and Kaufman. Dr. krupp has received intellectual property interests from a discovery or technology relating to health care.
Amit Bar-Or, MD, FRCPC (University of Pennsylvania)	Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for cabaletta. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech.
Joanna Evershed, Industry	Mrs. Evershed has received personal compensation for serving as an employee of Roche Products Ltd. Mrs. Evershed has stock in Roche Products Ltd.
Bouchra El Azzouzi (F. Hoffmann-La Roche Ltd, Basel, Switzerland)	No disclosure on file
Qing Wang	Qing Wang has nothing to disclose.
Chien-Ju Lin	Chien-Ju Lin has nothing to disclose.
Alexandra Hogea, PhD	Mrs. Hogea has received personal compensation for serving as an employee of Roche Products Ltd. Mrs. Hogea has stock in Roche Products Ltd.
Hans-Martin Schneble, MD (Roche)	Dr. Schneble has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd.. Dr. Schneble has received stock or an ownership interest from F. Hoffmann-La Roche, Ltd..
Corinne Manlius, MSc	Mrs. Manlius has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd.
Emmanuelle Waubant, MD, PhD, FAAN (USCF MS Center)	The institution of Dr. Waubant has received research support from NIH. The institution of Dr. Waubant has received research support from NMSS. The institution of Dr. Waubant has received research support from PCORI. The institution of Dr. Waubant has received research support from Race to Erase MS. The institution of Dr. Waubant has received research support from Roche. The institution of Dr. Waubant has received research support from Department of Defense. Dr. Waubant has received publishing royalties from a publication relating to health care.

��ɫ��

��ɫ��