Ocrevus Zunovo (ocrelizumab and hyaluronidase-ocsq) for multiple sclerosis

Last updated Sept. 18, 2024, by Ines Martins, PhD
Fact-checked by Patricia Silva, PhD

 

What is Ocrevus Zunovo for MS?

Ocrevus Zunovo (ocrelizumab and hyaluronidase-ocsq) is an injectable antibody-based therapy approved for adults with relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS), along with primary progressive multiple sclerosis (PPMS).

 

Given via a 10-minute injection under the skin, or subcutaneously, the treatment is expected to reduce relapses and brain lesions, and slow disability progression.

Ocrevus Zunovo was developed by Genentech, a member of the Roche Group, as a more convenient treatment option for patients who are already taking or considering Ocrevus (ocrelizumab), a similar medication that’s administered via intravenous infusion, or into the bloodstream.

Therapy snapshot

Brand name:	Ocrevus Zunovo
Chemical name:	Ocrelizumab and hyaluronidase-ocsq
Usage:	Used to reduce disease activity and slow disability accumulation in relapsing forms of MS and PPMS
Administration:	Subcutaneous injection

 

How does Ocrevus Zunovo work?

MS is an autoimmune disease wherein the immune system erroneously attacks and destroys myelin, a fatty substance around nerve fibers that is essential for the rapid transmission of nerve signals. While many immune cells are involved in this autoimmune attack, B-cells and T-cells are believed to be the main drivers of MS-related inflammation.

Like Ocrevus, Ocrevus Zunovo is an antibody therapy that targets the CD20 protein, found at the surface of B-cells. Once the antibody binds to CD20, it results in the cells’ rapid elimination, which is expected to ease MS-driving inflammation.

In addition to B-cells, evidence suggests ocrelizumab, the active agent in Ocrevus Zunovo, may also eliminate a subset of T-cells in people with MS, potentially contributing to its efficacy.

Ocrevus Zunovo was developed using a technology from Halozyme Therapeutics called Enhanze that facilitates the delivery of biologic therapies typically administered via an intravenous infusion. The technology relies on the company’s proprietary recombinant human hyaluronidase PH20 enzyme to degrade hyaluronan, a large sugar molecule in the tissue under the skin. By increasing the tissue’s permeability, it allows ocrelizumab to be more easily absorbed into the bloodstream. This change in permeability is reversible and returns to normal in about one to two days after the injection.

Who can take Ocrevus Zunovo?

Ocrevus Zunovo was approved by the U.S. Food and Drug Administration in September 2024 for treating adults with relapsing forms of MS — including CIS, RRMS, and active SPMS — and PPMS.

The decision made Ocrevus Zunovo and Ocrevus the only two therapies in the U.S. approved for both relapsing MS and PPMS.

The medication has also been approved in the European Union and the U.K. for adults with relapsing forms of MS and active disease — as defined by certain clinical or imaging features — as well as PPMS.

Who should not take Ocrevus Zunovo?

Ocrevus Zunovo is contraindicated, or not recommended, for anyone with:

• an active hepatitis B virus infection
• a history of a life-threatening administration reaction to ocrelizumab
• a known allergy to ocrelizumab, hyaluronidase, or any other component in Ocrevus Zunovo.

How is Ocrevus Zunovo administered?

Ocrevus Zunovo is administered via a subcutaneous injection into the abdomen, which takes approximately 10 minutes. Injections are given every six months and should be administered by a healthcare professional only.

The therapy’s recommended dose is 920 mg ocrelizumab and 23,000 units of hyaluronidase, delivered in 23 mL of a clear to slightly opalescent and colorless to pale brown solution provided in a single-dose vial.

Before each injection, patients are pre-medicated with an anti-inflammatory corticosteroid and an antihistamine, given at least 30 minutes prior to reduce the risk of injection-related reactions. Anti-fever medications may also be considered.

Ocrevus Zunovo injections should be given into the abdomen, except for the region around the navel. The medication should not be administered into regions with moles or scars, or where the skin is red, bruised, tender, or hard.

Patients should be closely monitored during each injection and for at least one hour after the initial dose. The post-injection monitoring period can be reduced to at least 15 minutes for subsequent injections.

If patients miss a planned dose, Ocrevus Zunovo should be administered as soon as possible and the dosing schedule should be adjusted so the next dose is given six months after the missed dose.

Because Ocrevus Zunovo may decrease the effectiveness of vaccines, it’s recommended that patients receive all appropriate vaccinations at least two to four weeks before treatment is initiated. Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell levels return to normal.

 

Ocrevus Zunovo in clinical trials

Ocrevus Zunovo’s approval in the U.S. was supported by data from the three Phase 3 trials — OPERA I (NCT01247324), OPERA II (NCT01412333), and ORATORIO (NCT01194570) — that also formed the basis for the 2017 approval of Ocrevus.

The OPERA trials showed Ocrevus significantly lowered relapse rates, reduced brain lesions, and slowed disability progression in people with relapsing forms of MS compared with an older subcutaneous medication called Rebif (interferon beta-1a).

ORATORIO supported the breakthrough approval of Ocrevus for people with PPMS. It showed the therapy significantly delayed confirmed disability progression on the Expanded Disability Status Scale (EDSS) compared with a placebo, while also lowering the total volume of brain lesions.

The approval package also included data from a fourth Phase 3 study called OCARINA II that compared the safety, efficacy, and pharmacological properties of Ocrevus Zunovo with those of the original intravenous formulation.

OCARINA II

The OCARINA II Phase 3 trial (NCT05232825) enrolled 236 adults with relapsing forms of MS and PPMS to determine if Ocrevus Zunovo was at least as good as Ocrevus in a number of measures.

Participants, ages 18-65 and with a disease duration of up to 15 years, were randomly assigned to receive an initial 920 mg dose of the subcutaneous formulation or the approved 600 mg dose of Ocrevus, which is given initially in two intravenous infusions two weeks apart. Then, all received Ocrevus Zunovo every six months for up to two years.

Both formulations led to similar levels of ocrelizumab in the blood over the first three months, meeting the trial’s main goal. The majority of patients in each group, 97% on Ocrevus Zunovo and 98% on Ocrevus, had B-cell counts lower than 5 cells per microliter of blood within two weeks after the first dose. These low B-cell counts were sustained in most patients out to six months.

After 48 weeks, or nearly a year, more than 97% of patients in both groups were free from relapses — 97.2% of those who always received the subcutaneous formulation and 98.1% of patients who were initially treated with Ocrevus. The two formulations also led to a near-complete suppression of MRI disease activity, with most patients having no inflammatory lesions or new or enlarging lesions at week 48.

In a patient-reported outcome measure, the majority (92.3%) of patients were satisfied or very satisfied with Ocrevus Zunovo and felt the formulation was convenient or very convenient to use (90.1%). Most (90.5%) also said the time it took to get the injection was just right and they would recommend the subcutaneous route of administration to other patients (94.1%).

Safety data for both formulations were generally comparable and no new safety concerns were identified with Ocrevus Zunovo. The only notable difference was that more than half (51.5%) of those given the subcutaneous version had injection-related reactions, which were more frequent than the infusion-related reactions reported with Ocrevus. These reactions, however, were mostly mild or moderate in severity and none led to treatment discontinuation.

Common side effects of Ocrevus Zunovo

The most common side effects associated with Ocrevus Zunovo are injection reactions. Other adverse reactions that were common with the intravenous formulation in clinical trials and may also occur in people receiving Ocrevus Zunovo include:

• upper respiratory tract infections in people with relapsing MS
• upper and lower respiratory tract infections and skin infections in people with PPMS.

Injection reactions

Injection reactions associated with Ocrevus Zunovo can be localized, causing symptoms such as skin redness, pain, itching, and swelling, or systemic, leading to symptoms like headache and nausea. Patients should be closely monitored during and after injections, and given oral premedication to reduce the risk of these reactions.

If a life-threatening reaction occurs, Ocrevus Zunovo should be stopped immediately and not restarted, and the patient should receive appropriate supportive care as needed. In cases of less severe reactions, the injection should be paused and the patient should be treated to relieve their symptoms. The healthcare provider may choose to resume the injection only after all symptoms have resolved.

Low antibody levels and infections

Because Ocrevus Zunovo lowers the levels of B-cells, which produce antibodies that fight off microbes, people receiving the treatment may experience low levels of circulating antibodies, which can increase the risk of serious infections. Patients should be checked for antibody levels before initiating Ocrevus Zunovo, and then regularly during treatment and after discontinuation, until B-cell levels return to normal.

Clinical trials of intravenous ocrelizumab, the active ingredient in Ocrevus Zunovo, have found that the medication increases the risk of respiratory tract infections, skin infections, and herpes-related infections. In people with an active infection, Ocrevus Zunovo should not be administered until the infection is resolved. If patients experience serious opportunistic infections or recurrent serious infections, discontinuing treatment should be considered.

Progressive multifocal leukoencephalopathy

A rare viral brain infection called progressive multifocal leukoencephalopathy (PML), which usually leads to severe disability or death, has been reported in some patients who were treated with ocrelizumab and other CD20 inhibitors. If signs of PML appear, patients should pause Ocrevus Zunovo and an appropriate diagnostic evaluation should be performed. Treatment should be discontinued permanently if PML is confirmed.

Cancer

Treatment with Ocrevus Zunovo may increase the risk of malignancies, such as breast cancer. It’s recommended that patients follow standard screening guidelines that can detect breast cancer and other malignancies as early as possible.

Colitis

There have been reports of patients who developed immune-mediated colitis, a type of inflammation in the large intestine caused by a misguided immune system attack, after receiving Ocrevus. Some cases were serious and required hospitalization and surgery. Patients taking Ocrevus Zunovo should be monitored for this side effect, which may cause symptoms such as persistent diarrhea and other gastrointestinal problems.

Use in pregnancy and breastfeeding

There are no adequate studies on the use of Ocrevus Zunovo in people who are pregnant or breastfeeding, but evidence has shown that babies born to mothers who received other anti-CD20 antibodies during pregnancy may have lower than normal levels of B-cells and other white blood cells.

These babies should not receive vaccines containing live or live-attenuated viruses before their B-cell levels return to normal. Non-live vaccines may be administered, but the babies should be later assessed to determine if an adequate immune response was mounted.

It is generally recommended that people of childbearing age use effective birth control methods while receiving the medication and for at least six months after their last dose.

It’s not known whether ocrelizumab or hyaluronidase can pass into human breast milk or cause any harm to the nursing infant. Those who plan to breastfeed while on Ocrevus Zunovo should inform their healthcare provider and carefully weigh the potential benefits and risks of using the medication while nursing.

---

Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.