Ocrelizumab Gains EU CHMP Positive Opinion for Subcutaneous Formulation to Treat MS

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In the phase 3 OCARINA 2 trial, subcutaneous ocrelizumab was non-inferior to intravenous infusion based on concentration levels in the blood, as well as comparable efficacy on relapses and brain lesions.

Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche

Levi Garraway, MD, PhD

According to an announcement from Roche, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval for a subcutaneous (SC) administration of ocrelizumab (Ocrevus), the only marketed therapy to treat both progressive and relapsing multiple sclerosis (MS). A final decision on its approval from the EU is expected mid-2024.1

Data supporting the use of SC ocrelizumab stems from the phase 3 OCARINA 2 trial (NCT05232825), a global, randomized study that compared the pharmacokinetics of SC ocrelizumab with its intravenous (IV) infusion, the formulation for which it was approved in. Initial study data presented at MSMilan 2023, the joint ECTRIMS-ACTRIMS meeting, showed that a 920-mg SC dose formulation was comparable to its 600-mg IV counterpart in terms of clinical benefit.2

"More than 300,000 people with MS have been treated globally with twice-a-year OCREVUS IV infusions to date. However, access to IV facilities may be challenging for some patients, and, conversely, some MS centers have limited IV capacity,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in a statement.1 "The CHMP’s recommendation brings us a step closer to offering the 10-minute OCREVUS SC injection in the EU, expanding access to even more people with MS who could benefit from this treatment."

The belief is that if approved, a SC administration of ocrelizumab will provide treatment flexibility and additional treatment options for patients and healthcare providers. In OCARINA, the SC and IV administration led to similar exposure overall during the first 12 weeks of treatment for the 116 patients who received each therapy in the study, with 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). Additionally, the geometric mean ratio for the max concentration (Cmax) of 0.96 (90% CI, 0.92-1.01; subcutaneous Cmax, 132 µg/mL; IV Cmax, 137 µg/mL).2

READ MORE: Literature Review Demonstrates Ravulizumab’s Superior Efficacy Over Other Approved NMOSD Treatments

Additional data presented at MSMilan 2023 showed that 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. Both groups had a single patient report 1 relapse (0.9% of each group), for an unadjusted per year relapse rate of 0.02 for both groups. As for T1 gadolinium-enhancing lesions and T2 lesions, both groups reported similar baseline numbers—the subcutaneous group had 118 and 118, respectively, and the IV group had 118 and 118, respectively. By week 24, the T1 lesion counts were 49 for the subcutaneous group and 52 for the IV group, while T2 lesion counts were 61 and 65 for the 2 patient cohorts, respectively (week 8 adjusted lesion rate, 0.11 for subcutaneous, 0.12 for IV; week 24 adjusted lesion rate, 0.00 for both).

In safety analyses, which included 118 patients in each group, those on SC ocrelizumab reported more adverse events than the IV group (73.4% vs 45.8%), although no AEs led to withdrawal in either group. Serious AEs were comparable, with the SC group reporting a rate of 2.5% (n = 3) and the IV group reporting a rate of 3.4% (n = 4). Investigators concluded that the differences between the groups was driven by nonserious mild and moderate injection reactions, which were considered nontreatment limiting and resolved on their own, with only a handful of patients requiring treatment with analgesics and antihistamines.

Updated, longer-term results presented at the 2024 American Academy of Neurology (AAN) Annual Meeting showed near-complete suppression of clinical relapses and brain lesions in patients with relapsing or primary progressive MS for up to 48 weeks. In patients who continued on ocrelizumab SC or switched, 97.2% had no relapse during the treatment phase, and most patients had no T1 gadolinium-enhancing lesions and no new/enlarging T2 lesions. Additionally, in exploratory patient-reported outcome measures (n = 52) patients reported a high level of satisfaction (92.3% were satisfied or very satisfied) and convenience (90.1% felt it was convenient or very convenient) with ocrelizumab SC injection.3

REFERENCES
1. Roche’s OCREVUS subcutaneous injection receives EU CHMP positive opinion for relapsing and primary progressive multiple sclerosis. News release. Roche. April 29, 2024. Accessed April 30, 2024. https://www.roche.com/investors/updates/inv-update-2024-04-29
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.
3. Newsome S, Krzystanek E, Selmaj K, et al. OCARINA II phase 3 study: results of subcutaneous ocrelizumab administration in patients with multiple sclerosis. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO. ABSTRACT 003597
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