EU Approves Subcutaneous Formulation of Ocrelizumab for Multiple Sclerosis Treatment

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Data from the large-scale, phase 3 OCARINA 2 trial was the basis for the approval.

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

Levi Garraway, MD, PhD

According to a recent announcement, the European Commission (EU) has granted market authorization for a new subcutaneous formulation of ocrelizumab (Ocrevus; Roche), administered twice-yearly as a 10-minute injection for patients with multiple sclerosis (MS). The subcutaneous injection was designed to be administered by healthcare professionals, with the flexibility to administer either in the clinic or in settings outside the clinic.1

The newly approved formulation, which remains under review by the FDA, combines ocrelizumab with Halozyme Therapeutics’ EHANZE drug delivery technology. Ocrelizumab, a humanized monoclonal antibody designed to target CD20-positive B cells, remains the only approved therapy to treat both relapsing forms of MS and primary progressive MS (PPMS).

Ocrelizumab’s subcutaneous formulation was approved based on data from OCARINA 2, a phase 3, multicenter, randomized study (NCT05232825) that evaluated and compared the pharmacokinetics, safety, and clinical and radiological efficacy of the new formulation with its original intravenous (IV) infusion. The trial, which featured 236 patients with relapsing MS or PPMS, met its primary and secondary end points, demonstrating that subcutaneous in injection was non-inferior to IV infusion. In addition, the safety profile of the new administration was also consistent with the well-established safety profile of ocrelizumab IV.

"OCREVUS transformed the way multiple sclerosis is treated as the first anti-CD20 therapy approved in this disease. Now, people in the EU with multiple sclerosis can have their medicine administered in just 10 minutes twice per year without needing an IV facility,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in a statement.1 "This makes it easier for more people with multiple sclerosis to access their treatment, while also saving time for providers."

Ocrelizumab, a disease-modifying therapy, was originally approved in 2017. At the time, it was approved as an infusion, given in 300 mg doses over 2.5 hours, followed by an additional 300 mg IV infusion 14 days later. Subsequent doses were to be given every 6 months as a 600 mg IV infusion over 3.5 hours.

In OCRAINA 2, during the first 12 weeks of treatment, the subcutaneous and IV administration of ocrelizumab led to similar exposure, with a geometric mean ratio comparing both arm’s area under the curve (AUC) of 1.29 (95% CI, 1.23-1.35; subcutaneous AUC weeks 1-12, 3500 ug/mL per day; IV AUC weeks 1-12, 2750 ug/mL per day). Investigators also recorded a geometric mean ratio for the max concentration of 0.96 (90% CI, 0.92-1.01; subcutaneous Cmax, 132 ug/mL; IV Cmax, 137 ug/mL).2

Regarding clinical 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. 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).

Scott Newsome, DO

Scott Newsome, DO

In terms of safety, the subcutaneous group reported more adverse events (AEs), with a rate of 73.7% (n = 87) compared with 45.8% (n = 54) in the IV group. Serious AEs were comparable, with the subcutaneous group reporting a rate of 2.5% (n = 3) and the IV group reporting a rate of 3.4%. Injection reactions, which occurred in 54 patients (45.8%) on the subcutaneous treatment, included erythema (29.7%), pain (14.4%), swelling (8.5%), and pruritus (6.8%). Systemic injection reactions, which occurred in 13 patients (11%), comprised mainly of headache (2.5%) and nausea (1.7%).

Scott Newsome, DO, lead investigator of OCARINA 2, told NeurologyLive® earlier this year that, “The investigational 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,” Newsome director of the Stiff Person Syndrome Center and professor of neurology at Johns Hopkins Medicine, added, "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."

REFERENCES
1. Roche’s OCREVUS subcutaneous administration approved by European Commission, as first and only twice-a-year injection for relapsing and primary progressive multiples sclerosis. News release. Roche. June 25, 2024. Accessed June 28, 2024. https://www.globenewswire.com/news-release/2024/06/25/2903478/0/en/Roche-s-OCREVUS-subcutaneous-administration-approved-by-European-Commission-as-first-and-only-twice-a-year-injection-for-relapsing-and-primary-progressive-multiple-sclerosis.html
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.
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