Subcutaneous Ocrelizumab Provides New Administration Opportunities for Multiple Sclerosis

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Subcutaneous ocrelizumab can be delivered in approximately 10 minutes and deliver comparable clinical benefit and safety to the IV formulation.

Although intravenous (IV) ocrelizumab (Ocrevus; Genentech) is approved and highly efficacious for the treatment of patients with remitting multiple sclerosis (rMS) as well as primary progressive MS (PPMS), new research is opening up the opportunity for subcutaneous (SC) ocrelizumab, which provides a shorter administration time. New data, presented at the Consortium of Multiple Sclerosis Centers (CMSC) 2024 Annual Meeting, shows that the SC formulation has noninferior efficacy and safety when compared with the IV formulation.

More than 350,000 patients globally have been treated with IV ocrelizumab, which is supported by more than 10 years of clinical trial experience and more than 1,000,000 patient years. However, SC ocrelizumab can be delivered in approximately 10 minutes and deliver comparable clinical benefit and safety to the IV formulation. It is formulated with hyaluronidase to enable rapid delivery, according to CMSC presenter Scott D. Newsome, DO, MSCS.

Multiple sclerosis (MS): microglia cells damage the myelin sheath of neuron axons.

Image credit: Juan Gärtner | stock.adobe.com

The SC ocrelizumab clinical development program consists of the OCARINA 1 and 2 trials. The OCARINA 1 trial was a phase 1b, dose-finding study with a dose escalation up to 1200 mg. Newsome said investigators originally thought the 1200 mg dose would be necessary to proceed to the OCARINA 2 noninferiority study, but ocrelizumab SC 920 mg was ultimately selected. OCARINA 2 is a pharmacokinetic noninferiority study of ocrelizumab SC 920 mg compared with ocrelizumab IV 60 mg.

The patient population in the OCARINA 2 trial included patients with rMS or PPMS aged 18 to 65 years, with an Expanded Disability Status Scale (EDSS) score between 0.0 and 6.5 and who were naïve to ocrelizumab and anti-CD20 agents. Newsome noted that the only difference between the cohorts in the 2 trials was that in OCARINA 1, there was 1 cohort that was not treatment naïve. Baseline demographics and disease characteristics in OCARINA 2 were reflective of the broad MS population for which ocrelizumab IV is indicated.

Investigators saw sustained B-cell depletion with suppression of both clinical and MRI disease activity among patients receiving SC ocrelizumab. The B-cell depletion levels were similar with ocrelizumab SC and IV routes.

Newsome primarily focused on the safety data in the SC all exposure group, meaning all patients who received at least 1 injection of the SC formulation. Of the 233 total patients in this group, 175 (75.1%) experienced adverse events (AEs), most of which were grade 1 or grade 2. Six patients (2.6%) experienced serious AEs, 89 (38.2%) experienced infections, 120 (51.5%) experienced infusion reactions, 117 (50.2%) experienced local infusion reactions, and 27 (11.6%) experienced systemic infusion reactions. Over the 48 weeks, ocrelizumab SC was well tolerated and no new safety concerns were identified beyond the known risks associated with ocrelizumab or the new route of administration.

The serious AEs included anxiety (1); eye pain (1); hemorrhagic ovarian cyst (1); urinary tract infection (1); MS pseudo relapse (2); MS relapse (1); intentional self-injury (1); and leukopenia, neutropenia, and pyrexia (in the same patient). In those who experienced at least 1 infusion reaction at the first injection, all reactions were grade 1 (76%) or grade 2 (24%) and the majority required no treatment with a median duration of 2 days. Incidence and severity of infusion reactions decreased after the first injection and no reaction led to treatment discontinuation. Finally, Newsome said the most common symptoms of systemic infusion reactions were headache (2.1%), flushing (1.3%), and nausea (1.3%).

Additionally, no new safety concerns were identified with a shortened premedication timing. Participants received a mandatory dexamethasone 20 mg and desloratadine 5 mg before treatment, as well as acetaminophen as needed. This premedication was originally 1 to 2 hours before ocrelizumab administration, but due to the lack of infusion reactions this was amended to 0 to 60 minutes before injection.

Patients reported positive experiences with the ocrelizumab SC injections at week 48, based on a questionnaire completed 30 to 60 minutes after ocrelizumab administration. According to the study results, 92.3% of patients were either satisfied or very satisfied with the SC procedure and 90.1% felt that the SC procedure was convenient or very convenient. Additionally, 91% reported experiencing no pain or mild pain during the SC injection process and 87.4% experienced no pain or mild pain at the site of the injection.

As ocrelizumab looks toward shifting to availability of a SC formulation, pharmacists will certainly play a key role in educating patients about proper use and administration. Pharmacists have plenty of experience educating patients on using subcutaneous medications, such as with insulin or new glucagon-like peptide-1 medications. Researchers have found that pharmacists can effectively and safely help patients transition from IV to SC medications.

For instance, one study published in the American Journal of Health-System Pharmacists found that a pharmacist-managed protocol for transitioning critically ill patients from IV to SC insulin was successful. The single-center, retrospective, observational study found that pharmacists were able to achieve blood glucose concentrations in the target range for 53% of IV-to-SC transitions at 12 hours, 40% at 24 hours, and 47% at 48 hours. The pharmacist-managed group had a low rate of hypoglycemia and no severe hypoglycemia, highlighting how pharmacists can support patient safety.2

With the new data supporting potential SC ocrelizumab for patients with MS, pharmacists can prepare to help with this potential future shift.

REFERENCES

1. Newsome SD. Ocrelizumab Administered Subcutaneously: Results from the Clinical Development Program. Presented at: Consortium of Multiple Sclerosis Centers 2024 Annual Meeting. May 29–June 1, 2024; Nashville, Tennessee.

2. Gerhardt JM, Dine SA, Foster DR, et al. Development of a pharmacist-managed protocol for the transition from intravenous to subcutaneous insulin in critically ill adults. Am J Health Syst Pharm. 2022;79(Suppl_3)LS86-S93. doi:10.1093/ajhp/zxac141

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