Gaining Clinical Insights Into the Benefits of Subcutaneous Ocrelizumab

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Scott Newsome, DO, director of the Stiff Person Syndrome Center and professor of neurology at Johns Hopkins Medicine, provided clarity on the 1-year data of the OCARINA II study assessing subcutaneous ocrelizumab.

Scott Newsome, DO, lead investigator of OCARINA II

Scott Newsome, DO

In 2017, ocrelizumab (Ocrevus; Genentech) made history, becoming the first approved therapy to treat adult patients with primary progressive multiple sclerosis (MS), a steadily declining version of the disease. At the time, it was approved as an infusion, given in 300 mg doses over 2.5 hours, followed by an additional 300 mg intravenous infusion 14 days later. Subsequent doses are given every 6 months as a 600 mg intravenous infusion over 3.5 hours.

Ocrelizumab, a humanized monoclonal antibody designed to target CD20-positive B cells, is currently being assessed in the phase 3 OCARINA II trial (NCT05232825), a global randomized study of 236 patients with relapsing or primary progressive MS. The trial specifically evaluates the pharmacokinetics, safety, and radiological and clinical effects of a subcutaneous formulation of ocrelizumab compared with its original intravenous infusion. Updated, long-term term results showed that ocrelizumab subcutaneous injection resulted in near-complete suppression of relapse activity (97.2% had no relapse during the treatment phase) and MRI up to 48 weeks with an annualized relapse rate of 0.04, and most patients having no gadolinium-enhancing lesions and no new/enlarging T2 lesions.

Presented at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, these data were part of an accepted submission to the FDA and the European Medicines Agency for a new subcutaneous formulation of ocrelizumab. While both are expected to give their answer back later this year, NeurologyLive® reached out to Scott Newsome, DO, lead investigator of OCARINA II, to discuss the recently presented data. Newsome, director of the Stiff Person Syndrome Center and professor of neurology at Johns Hopkins Medicine, gave some insight on the promise behind subcutaneous ocrelizumab, the advantages it holds over the previously approved formulation, and whether it may be more effective for patients going forward.

NeurologyLive: How was OCARINA II was conducted? What went into patient inclusion criteria?

Scott Newsome, DO: This was a Phase III non-inferiority, randomized, open-label, parallel group, multicenter study to evaluate the pharmacokinetics, pharmacodynamics, safety, immunogenicity, radiological, and clinical effects of subcutaneous (SC) administration of Ocrevus (ocrelizumab). The patient population included were representative of individuals who are currently receiving commercially available Ocrevus IV. This is important in order to make the results of the trial generalizable.

Discuss some of the major findings; what were the greatest takeaways from a clinical perspective?

Firstly, the OCARINA II study investigated a convenient and quickly administered, new formulation of Ocrevus that was given as a twice-yearly, approximately 10-minute subcutaneous injection (OCR SC). OCR SC showed near-complete suppression of disease activity in people with relapsing or primary progressive multiple sclerosis (RMS or PPMS) which reinforce the potential benefits of this investigational formulation.

Specifically, there was a robust reduction in relapse activity (97%) and MRI lesions (97.2%) through 48 weeks.

The investigational OCR SC is designed to be administered by a healthcare provider without the need for IV infrastructure, so it has the potential to expand the usage of Ocrevus in areas without IV infrastructure or those with IV capacity limitations.

What advantages are there to subcutaneous ocrelizumab vs IV formulation?

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. 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.

How do we build on this data? Where do we go from here?

Both the U.S. FDA and EMA have accepted filings based on the data from OCARINA II, and the EU submission received a positive CHMP opinion on April 30, with EU approval anticipated mid-2024 and U.S. approval anticipated September 2024. If approved, we will be able to get real-world experience with this formulation and see how well it is adopted within the community. Based on the clinical trial program, I suspect many HCPs and patients will welcome such a therapy.

Do we know if subcutaneous routes of administration may have more success in penetrating the blood-brain barrier?

At present, we do not have CSF concentration data from the OCARINA clinical trial program, so we can’t make any conclusions here. Nonetheless, OCARINA II results shared at AAN 2024 demonstrated that Ocrevus SC resulted in rapid and near-complete suppression of MRI and relapse activity (97% had no relapse during the treatment phase or safety follow up) up to 48 weeks with an ARR of 0.04, and most patients having no T1 gadolinium-enhancing (T1 Gd+) lesions and no new/enlarging T2 lesions. These data demonstrate what we are accustomed to with B-cell depletion therapies.

What are your thoughts on the EU CHMP’s recent decision to recommend approval for subcutaneous ocrelizumab?

It is very exciting since this will bring a highly efficacious therapy that is convenient and quick to administer to patients who are great candidates for such a therapy. It opens the doors for patients who are great candidates for a high-efficacy therapy but unable to obtain in certain regions of the world due to limitations with accessing IV therapies.

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