Ocrevus Zunovo now approved in US to treat relapsing MS, PPMS
Under-skin injection takes 10 minutes, not 2-4 hours like into-vein therapy
The U.S. Food and Drug Administration (FDA) has approved Ocrevus Zunovo (ocrelizumab and hyaluronidase-ocsq), a subcutaneous, or under-the-skin, formulation of Ocrevus (ocrelizumab), for treating adults with multiple sclerosis (MS).
The approval covers all the same indications as the original medication, including relapsing forms of MS — namely clinically isolated syndrome, relapsing-remitting MS, and active secondary progressive MS — as well as primary progressive MS (PPMS). This makes Genentech‘s Ocrevus and Ocrevus Zunovo the only two therapies in the U.S. approved to treat both relapsing MS and PPMS.
Following similar approvals in the European Union and the U.K., the decision means that U.S. MS patients will now be able to receive ocrelizumab via an under-the-skin injection that takes only 10 minutes, compared with the two- to four-hour intravenous (IV or into-the-vein) infusions needed for the original Ocrevus formulation.
“Ocrevus Zunovo gives patients and providers another option for receiving Ocrevus, building on a decade of robust safety and efficacy data for Ocrevus in multiple sclerosis,” Levi Garraway, MD, PhD, Genentech’s chief medical officer and head of global product development, said in a company press release. “[This] approval may offer greater flexibility for healthcare providers and people living with multiple sclerosis, based on their individual treatment needs.”
Specifically, Genentech noted in the release that “Ocrevus Zunovo has the potential to expand treatment options to centers without IV infrastructure or with IV constraints, like at a doctor’s office.”
Total treatment time with new formulation may be as little as 55 minutes
Ocrevus is an antibody-based medication that blocks the CD20 protein found at the surface of B-cells, a type of immune cell that contributes to MS-driving inflammation. By reducing B-cell levels, the treatment is expected to help reduce disease activity and slow disability progression.
Despite its proven efficacy, Ocrevus requires long infusion times, and may not be easily accessible to everyone who needs it. Some patients may have difficulties accessing infusion facilities, and some centers also have limited capacity to deliver such infusion medications.
The new formulation includes ocrelizumab, the active ingredient in Ocrevus, plus a lab-made version of an enzyme called human hyaluronidase PH20, which breaks up certain large sugar molecules in the space under the skin to increase the absorption of injectable therapies into the bloodstream. This makes it possible to administer infusion therapies via a more convenient and patient-friendly subcutaneous injection, according to the developer.
Ocrevus Zunovo will be given via a subcutaneous injection into the abdomen every six months. The treatment should still be given by a healthcare professional, but this can be done outside the clinic. Patients must receive certain premedications at least 30 minutes before each dose, per Genentech.
Each injection contains 920 mg of ocrelizumab and 23,000 units of hyaluronidase. The treatment is preceded by premedication with corticosteroids and an antihistamine a half hour prior to reduce the risk of injection reactions. Patients should also be monitored for one hour after the initial injection, and 15 minutes in subsequent injections, bringing the total treatment time to as little as 55 minutes.
It’s crucial to acknowledge each experience with MS is as unique as the individual navigating it, so providing choices to address each person’s needs is essential. We are pleased that with a new method of delivery, there is now an additional option for those who need flexibility in the route of administration or treatment time.
“People are living longer with chronic illnesses and with fewer disabilities because of the extensive progress that has been made in the development of medicines that can slow their progression,” said Natalie Blake, executive director of the Multiple Sclerosis Foundation, also known as MS Focus.
“But still, not everyone has access to these medicines,” Blake said. “It’s crucial to acknowledge each experience with MS is as unique as the individual navigating it, so providing choices to address each person’s needs is essential. We are pleased that with a new method of delivery, there is now an additional option for those who need flexibility in the route of administration or treatment time.”
US approval of Ocrevus Zunovo based on OCARINA II trial data
The approval of Ocrevus Zunovo was based on data from the OCARINA II Phase 3 trial (NCT05232825), which compared the safety, efficacy, and pharmacological properties of the new formulation with those of intravenous Ocrevus in 236 adults with relapsing forms of MS and PPMS.
Participants were randomly assigned to receive an initial 920 mg dose of the subcutaneous formulation, or the approved 600 mg dose of Ocrevus, which was given in two intravenous infusions two weeks apart. Then, after 24 weeks (about six months), all patients received Ocrevus Zunovo every six months for about two years.
Both formulations resulted in similar levels of ocrelizumab in the bloodstream and induced similar reductions in B-cell levels in the first weeks after dosing, the data showed.
After 48 weeks, or nearly one year, most patients on either formulation were free from relapses and the vast majority also had no signs of MRI disease activity. Moreover, about 92% of patients reported being satisfied or very satisfied with the new subcutaneous administration, and 90% also said the formulation was convenient or very convenient.
While the safety profile of Ocrevus Zunovo was similar to that of Ocrevus, injection reactions were more common with the new formulation, reported by 49% of patients after the first injection. Still, these reactions were mild or moderate and none led to treatment discontinuation.
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