(DMT02) Ocrelizumab Dose Selection for Treatment of Pediatric Relapsing-Remitting Multiple Sclerosis: Pharmacokinetic, Safety, and Efficacy Results From OPERETTA 1.

BACKGROUND: Pediatric multiple sclerosis (MS) is a highly active disease with frequent relapses and rapid accrual of MRI lesions occurring early in the disease course. Current pediatric treatment strategies are largely based on those used in adults, and treatment optimization is required. Ocrelizumab (OCR) may improve treatment adherence and outcomes, offering a new treatment option for pediatric patients with MS (PwMS). OBJECTIVES: To select the OCR dosing regimen for patients with pediatric relapsing-remitting MS (RRMS), with a pharmacokinetic/ pharmacodynamic (PK/PD) and safety profile similar to adults treated at the approved intravenous dose of 600 mg. METHODS: Patients aged ≥ 10 to < 18 years with RRMS in OPERETTA 1 (NCT04075266) were randomly assigned into cohort 1 (body weight < 40 kg; OCR 300 mg) or cohort 2 (body weight ≥ 40 kg; OCR 600 mg) for a 24-week (24W) dose-exploration period (DEP) followed by an optional OCR extension (OOE) with OCR given at 24W intervals. PK, PD, and safety were assessed. Exploratory efficacy end points include protocol-defined relapses and MRI activity (new T1 gadolinium-enhancing [T1-Gd] lesions at 12W and new/enlarging T2 [n/e T2] lesions at 12W, 24W, and every 24W thereafter). RESULTS: As of October 2023, 23 patients (cohort 1, n = 6; cohort 2, n = 17) completed the 24W DEP. Following initiation of OCR treatment, no clinical relapses were reported. No new T1-Gd lesions were reported at 12W; n/e T2 lesions were observed in 15 patients at 12W, 3 patients at 24W, 1 patient at 48W, 0 at 96W, and 1 patient at 144W, with none reported in patients who completed 192W. All blood samples were antidrug-antibody negative. The observed OCR PK/ PD profile was consistent with adult data. The safety profile was similar to that seen in adults. Infusion-related reactions were mostly mild to moderate (grade 1, n = 10; grade 2, n = 6; grade 3 [nonserious], n = 1); most occurred at the first dose. Serious adverse events occurred in 5 patients. There were no new safety signals. One patient discontinued treatment following withdrawal of consent during OOE. CONCLUSIONS: The observed safety profile and the PK/PD data in pediatric patients treated with either 300-mg or 600-mg ocrelizumab was consistent with those seen in adult patients with MS. No relapses have been reported to date. A dosing regimen of 300 mg for patients < 35 kg body weight, and 600 mg for patients ≥ 35 kg, administered every 6 months, was selected to be investigated further in the phase 3 OPERETTA 2 trial (NCT05123703), which is actively recruiting. [ABSTRACT FROM AUTHOR]