Abstract Details

OCR is an effective treatment for people with relapsing and primary progressive multiple sclerosis (RMS/PPMS). The currently available formulation is administered IV every 6 months. A novel OCR SC formulation in combination with recombinant human hyaluronidase (rHuPH20) is being developed.

To report the results of OCARINA II (NCT05232825), a Phase III, randomized, open-label, controlled study designed to demonstrate non-inferiority in serum exposure of ocrelizumab (OCR) when administered via subcutaneous (SC) versus intravenous (IV) routes.

Patients with RMS/PPMS (18?65 years; Expanded Disability Status Scale score 0–6.5) were randomized (1:1) to receive OCR 600mg IV or 920mg OCR SC (selected based on pharmacokinetic data from the OCARINA I study [NCT03972306]). Study endpoints: comparison of serum OCR area under the concentration-time curve from baseline to Week 12 (AUC_W1?12), MRI lesion activity, number of relapses, immunogenicity, B-cell depletion and safety.

Baseline demographics and disease characteristics were balanced (OCR SC: n=118; 89.0% RMS, 9.3% PPMS; OCR IV: n=118; 89.8% RMS, 10.2% PPMS). At Week (W) 12, the geometric mean ratio (90% CI) for AUC_W1?12 of OCR SC versus IV was 1.29 (1.23?1.35). OCR SC 920mg resulted in near-complete suppression of MRI and relapse activity up to W24, similar to OCR IV. In both cohorts, treatment with OCR led to rapid and sustained B-cell depletion. The safety profile of OCR SC was consistent with that of OCR IV; both were well tolerated. No new safety concerns were identified in addition to the known risks associated with OCR or SC administration. No OCR-antidrug antibodies or antibodies to rHuPH20 were detected. Data up to W48 will be presented.

Ocrelizumab SC 920mg demonstrated non-inferiority to IV 600mg with respect to AUC_W1?12, and similar clinical and imaging measures. SC administration of ocrelizumab provides treatment flexibility and additional treatment options for patients and healthcare providers.