Updated OCARINA II Trial Data Highlights Therapeutic Benefits of Subcutaneous Ocrelizumab

Key Takeaways

Subcutaneous ocrelizumab demonstrated high patient satisfaction and near-complete relapse suppression in MS patients, with 99% relapse-free by week 24.
The 920-mg SC dose was noninferior to the 600-mg IV dose, offering a quicker, more accessible administration option.
Safety data indicated manageable adverse events, with no serious injection reactions or treatment-emergent antidrug antibodies.
SC administration addresses challenges like limited IV capacity and poor venous access, potentially expanding patient access to therapy.

Overall, 81.6% of patients preferred ocrelizumab over other MS treatments, with 98.1% satisfied with it overall by week 48.

Scott D. Newsome, DO

Using a clinical cut-off date (CCOD) up to September 2024, new findings from the phase 3 OCARINA II study (NCT05232825) continued to showcase the therapeutic potential of subcutaneous (SC) ocrelizumab (Zunovo; Roche), as patients with multiple sclerosis (MS) expressed a high level of satisfaction with this newer route of administration.¹

In the analysis, investigators aimed to further characterize the benefit-risk profile of SC ocrelizumab based on updated efficacy/safety data and new patient-reported outcomes using the new CCOD. Presented at the 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 27-March 1 in West Palm Beach, Florida, treatment with SC ocrelizumab resulted in near-complete suppression of relapse activity up to week 48, with 97.2% of patients who continued SC treatment and 98.1% of patients who switched from intravenous (IV) to SC treatment being relapse-free.

OCARINA II, the trial that led to the approval of SC ocrelizumab, included a 24-week double-blind period where patients received either SC ocrelizumab 920 mg or IV ocrelizumab 600 mg, followed by an open-label extension lasting up to 96 weeks. At week 48, using the Multiple Sclerosis Treatment Preference Questionnaire (MSTPQ), 81.6% of patients previously treated for MS had preferred ocrelizumab, and that 98.1% were satisfied or very satisfied overall with ocrelizumab as an MS treatment.

Led by Scott D. Newsome, DO, director of the Stiff Person Syndrome Center and professor of neurology at Johns Hopkins Medicine, 80.4% of patients who experienced both the IV and SC formulations of ocrelizumab claimed that they preferred SC administration, according to results on the Patient Preference Questionnaire. In terms of safety, using a CCOD of December 2023, adverse events (AEs) were recorded in 75.1% of patients on SC treatment, with serious AEs found in 2.6% and injection reaction (IR) documented in 51.5% of patients.

In the analysis, all IRs were considered not serious and mild/moderate in intensity, with 74.1% resolved, mostly within 3 days. Investigators reported no treatment-emergent antidrug antibodies to ocrelizumab, as well as small decreases in mean immunoglobulin G and M levels in both arms. Notably, the incidence of treatment-emergent anti-rHuPH20 antibodies was 0.4%.

Top Clinical Takeaways

1. The OCARINA II study showed that 97.2% of patients continuing subcutaneous ocrelizumab treatment were relapse-free at week 48.

2. 81.6% of patients preferred ocrelizumab over other MS treatments, with 98.1% satisfied with it overall by week 48.

3. Subcutaneous ocrelizumab was found to be noninferior to the IV formulation, achieving a geometric mean ratio of 1.29 in the bioequivalence study.

In mid-2024, when asked about some of the advantages of SC ocrelizumab, Newsome told NeurologyLive that the new formulation, "is an approximately 10-minute injection, compared to the current approved IV-formulation which is administered over 2- or 3.5 hours. Accessing IV administration may be challenging for some patients, especially if they do not live close to an infusion center or have poor venous access. Additionally, some MS centers have limited IV capacity or no access to IV infrastructure. Therefore, the 10-minute Ocrevus subcutaneous injection could potentially expand access to even more patients who could benefit from this highly efficacious therapy."

SC ocrelizumab was formally approved by the FDA months after that conversation, with data from OCARINA II as the supportive evidence. Overall, the bioequivalence study achieved its primary end point of demonstrating noninferiority of a 920-mg dose of SC therapy to the previously approved 600-mg IV dose. In the study, Investigators recorded a geometric mean ratio comparing both arm’s area under the curve (AUC) of 1.29 (90% CI, 1.23-1.35; subcutaneous AUC weeks 1-12, 3500 µg/mL per day; IV AUC weeks 1-12, 2750 µg/mL per day) over the first 12 weeks of treatment. Regarding disease activity, 99% of patients experienced no relapses during the study period up to week 24, with 106 and 105 patients in the subcutaneous and IV groups, respectively, reporting none.²

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REFERENCES
1. Newsome SD, Goldstick L, Selmaj K, et al. P089. Ocrelizumab Subcutaneous Administration: Further Characterization of the Benefit‒Risk Profile From the OCARINA II Study and Patient Preferences. Presented at: 2025 ACTRIMS Forum; February 27-March 1; West Palm Beach, FL. ABSTRACT P089.
2. Newsome SD. Subcutaneous Ocrelizumab in Patients With Multiple Sclerosis: Results of the Phase III OCARINA II Study. Presented at: MSMilan; October 11-13, 2023; Milan, Italy. POSTER P370.