Safety and Pharmacokinetic Profile of Ocrelizumab in Pediatric MS Mirrors Adult Population

Author(s):

In comparison with adults on ocrelizumab, pediatric patients experienced no clinical relapses and a safety profile that was similar to what was previously observed.

Teri Schreiner, MD, FAAN

In new data from the OPERETTA 1 study (NCT04075266), a study of pediatric patients with relapsing-remitting multiple sclerosis (RRMS), ocrelizumab (Ocrevus; Genentech) demonstrated a safety and pharmacokinetic/pharmacodynamic (PK/PD) profile that was similar to that seen in adult patients with the disease. All told, the data identified optimal dosing ranges that will be further evaluated in the phase 3 OPERETTA 2 trial (NCT05123703), which is actively recruiting.¹

A total of 23 patients with RRMS, aged 10 to 18 years old, completed the 24-week dose-exploration period, where they were randomly assigned to either cohort 1 (body weight <40 kg; ocrelizumab 300 mg dose) or cohort 2 (body weight ≥40 kg; ocrelizumab 300 mg dose). Among the 6 patients in cohort 1 and 17 in cohort 2 who finished the treatment period, there were no clinical relapses reported and no new safety signals observed.

Led by Teri Schreiner, MD, FAAN, an associate professor of pediatrics-neurology at the University of Colorado School of Medicine, the observed PK/PD profile of ocrelizumab in this pediatric population was similar to that seen in adults. In addition, no new T1-gadolinium-enhancing lesions were reported at week 12. Newly enlarging T2 lesions were observed in 15 patients at week 12, 3 patients at week 24, 1 patient at week 48, 0 at week 96, and 1 patient at 144 weeks. Notably, there were no reported newly enlarging T2 lesions observed in patients who completed 192 weeks of ocrelizumab treatment.

Presented at the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 29-June 2, in Nashville, Tennessee, results showed that the safety profile of ocrelizumab in pediatric RRMS was similar to that reported in adults with the disease. Infusion-related reactions were mostly mild to moderate (grade 1: n = 10; grade 2: n = 6; grade 3 [nonserious]: n = 1). Of note, 1 patient discontinued treatment following withdrawal of consent during the optional extension period.

OPERETTA 2, a follow up to OPERETTA, is an actively recruiting, double-blind, double-dummy study that evaluates the efficacy and safety of ocrelizumab compared with fingolimod (Gilenya; Novartis), another FDA-approved disease-modifying therapy, in children and adolescents with RRMS aged between 10 and 18 years. The study, which spans 96 weeks of treatment, uses number of relapses during the blinded-treatment part as the primary end point. Other end points include changes detected by brain scans, number and seriousness of adverse events, how the body breaks down and gets rid of ocrelizumab, and how treatment affects the immune system.²

Ocrelizumab, a humanized monoclonal antibody designed to target CD20-positive B cells, was approved as infusion, given in 300 mg doses over 2.5 hours, followed by an additional 300 mg intravenous infusion 14 days later. Recently, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended approval for a subcutaneous administration of the therapy, using data from the phase 3 OCARINA 2 trial (NCT05232825) as supporting evidence. The EU is expected to make a final decision on the new administration route in mid-2024.³

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REFERENCES
1. 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.
2. A clinical trial to compare the safety and effectiveness of ocrelizumab with fingolimod in children and young people with relapsing-remitting multiple sclerosis (RRMS). Roche. https://forpatients.roche.com/en/trials/autoimmune-disorder/multiple-sclerosis/a-study-to-evaluate-safety-and-efficacy-of-ocrelizumab--72268.html. Accessed May 30, 2024.
3. Roche’s OCREVUS subcutaneous injection receives EU CHMP positive opinion for relapsing and primary progressive multiple sclerosis. News release. Roche. April 29, 2024. Accessed May 30, 2024. https://www.roche.com/investors/updates/inv-update-2024-04-29