Subcutaneous Ocrelizumab Not Inferior to IV Infusion

MILAN — An investigational 10-minute subcutaneous injection of ocrelizumab (Ocrevus) was non-inferior to the established IV infusion formulation of the drug in multiple sclerosis (MS), the phase III OCARINA II trial showed.

During the first 12 weeks of treatment, blood levels of ocrelizumab — measured as the area under the serum concentration time curve (AUC) — were 3,500 day µg/mL for the subcutaneous injection and 2,750 day µg/mL for IV infusion (geometric mean ratio 1.29, 90% CI 1.23-1.35), reported Scott Newsome, DO, of Johns Hopkins University School of Medicine in Baltimore, at the joint meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Peak serum concentrations appeared similar for subcutaneous injection (132 µg/mL) and IV infusion (137 µg/mL), Newsome said in a late-breaking session. Both formulations provided rapid B-cell depletion: 97% of subcutaneous injection and 98% of IV infusion patients had B-cell levels of 5 cells/µL or less when first measured at 14 days, which was sustained over 24 weeks.

Both the injection and infusion formulations suppressed MRI lesion activity, with most patients having no T1 gadolinium-enhancing (T1 Gd+) lesions and no new or enlarging T2 lesions at 24 weeks. In both groups, 99% of patients had no relapse up to week 24.

The 10-minute subcutaneous injection of ocrelizumab is administered by a healthcare provider and designed to be delivered without the need for IV infrastructure, Newsome pointed out.

Ocrelizumab is a humanized monoclonal antibody designed to target CD20-positive B cells. The IV infusion formulation of ocrelizumab was approved in 2017 for relapsing and primary progressive forms of MS.

OCARINA II randomized 236 MS patients to 920 mg subcutaneous injection (118 participants) or 600 mg IV infusion (118 participants). Infusions were administered at 300 mg at two IV sessions, 2 weeks apart. At week 24, all participants were scheduled to receive 920 mg of ocrelizumab subcutaneously every 24 weeks up to week 96.

The primary objective was to evaluate the non-inferiority of subcutaneous versus IV ocrelizumab with respect to AUC over 12 weeks. A total of 63 participants in each group completed assessments at week 24.

Mean age at baseline was about 40, median weight was about 73 kg, and most participants were women. About 90% of participants had relapsing MS and 10% had primary progressive disease. Mean duration since MS diagnosis was around 5 years.

At baseline, the mean number of T1 Gd+ lesions was 0.54 in the subcutaneous group and 0.98 in the IV infusion group. About 70% of participants in the subcutaneous group and 66% in the infusion group had T1 Gd+ lesions at baseline.

Mean baseline T2 lesions were 44.48 for the subcutaneous group and 49.84 for the infusion group. Mean baseline scores on the Expanded Disability Status Scale (EDSS) were 2.5 in the subcutaneous group and 3.0 in the IV infusion group.

The safety profile of the ocrelizumab subcutaneous injection was consistent with the established safety profile of the IV infusion formulation and no new safety signals were identified.

Overall, 73.7% of people in the subcutaneous group and 45.8% in the IV infusion group experienced adverse events. The most common adverse events in the subcutaneous group were injection reactions, which affected 48.3% of exposed patients, all of which were mild or moderate. The most common adverse events in the IV infusion group were infusion-related reactions at 16.9%.

Four serious adverse events were reported for three participants in the subcutaneous group, and seven serious adverse events were reported for four participants in the IV infusion group. No new anti-drug antibodies to ocrelizumab were detected.

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