Ocrevus (ocrelizumab) for multiple sclerosis

 

What is Ocrevus used for?

Ocrevus (ocrelizumab) is an anti-CD20 therapy that reduces the risk of relapses and disability progression in people with multiple sclerosis (MS). It also lowers the number of new lesions on MRI scans.

The therapy was developed by Genentech, a member of the Roche Group.

Therapy Snapshot

Brand Name:	Ocrevus
Chemical Name:	Ocrelizumab
Usage:	Disease-modifying therapy for PPMS and relapsing forms of MS
Administration:	Intravenous infusion

 

How does Ocrevus work for MS?

In MS, the body’s immune system erroneously attacks healthy parts of the nervous system, namely the myelin sheath that covers nerve fibers and helps them send electrical signals efficiently. This inflammatory attack is driven by several types of immune cells, with B-cells and T-cells causing most MS-related damage.

The active agent in Ocrevus is a monoclonal antibody that targets the CD20 protein on the surface of mature B-cells, the cells responsible for antibody production, leading to their death.

Besides B-cells, research also has suggested that Ocrevus can reduce the number of pro-inflammatory T-cells in people with primary progressive multiple sclerosis (PPMS).

Who can take Ocrevus?

The U.S. Food and Drug Administration (FDA) approved Ocrevus in 2017 to treat adults in the U.S. with relapsing forms of MS — including clinically isolated syndrome, relapsing-remitting MS (RRMS), and active secondary progressive MS (SPMS).

In a groundbreaking move, the FDA also approved Ocrevus for PPMS, a progressive form of the disease for which no approved treatments yet existed. Ocrevus remains the only therapy approved for PPMS.

The European Commission approved Ocrevus in 2018 for adults with relapsing forms of MS and active disease — as defined by certain clinical or imaging features — and for PPMS.

Ocrevus is now approved in more than 95 countries for the treatment of MS, according to Roche.

Who should not take Ocrevus?

Ocrevus should not be given to people with an active hepatitis B virus infection. A blood test to rule out this infection should be performed before starting the medication.

Those who have had a life-threatening allergic reaction to Ocrevus or its components also should not receive the medication.

How is Ocrevus administered?

Ocrevus is administered via intravenous (into-the-vein) infusions. Its starting dose is given as two 300 mg infusions, two weeks apart. Subsequent doses, administered every six months thereafter, are given as a single 600 mg infusion.

Before each infusion, patients are pre-medicated with anti-inflammatory corticosteroids and antihistamines, and they are observed for at least an hour following each infusion. The total appointment time for each infusion ranges from four to six hours.

Ocrevus should be administered under the close supervision of an experienced healthcare professional. Possible infusion sites include:

• an infusion center
• the doctor’s office
• the patient’s home

Administration	Into-the-vein infusion
Dosage	Two 300 mg infusions initially; 600 mg infusion after initial dose
Timing	First two doses administered two weeks apart; subsequent dose given every six months

 

Ocrevus in PPMS clinical trials

The breakthrough approvals of Ocrevus for people with PPMS were based on data from the ORATORIO Phase 3 clinical trial (NCT01194570), which enrolled 732 people with the progressive form of the disease. Participants in this study received infusions of Ocrevus (600 mg) or a placebo every six months for at least 120 weeks (over two years).

Trial results showed that significantly fewer patients given Ocrevus had confirmed worsening of disability during the trial, compared with those on a placebo (32.9% vs. 39.3%). Overall, Ocrevus treatment reduced the risk of disability progression by about 24%. Disability worsening was defined as an increase in Expanded Disability Status Scale (EDSS) scores lasting at least three months.

Ocrevus also lowered the number of new brain lesions on MRI scans and prevented the loss of brain volume.

After completing ORATORIO, 544 patients opted for the trial’s open-label extension, in which all are receiving the therapy for eight years.

Findings from ORATORIO and its extension part, which is still collecting data, also showed that early and continuous use of Ocrevus can significantly slow disability progression in people with PPMS, as well as delay the time until patients require a wheelchair.

Ocrevus in relapsing MS clinical trials

Two similarly designed Phase 3 clinical trials, OPERA I (NCT01247324) and OPERA II (NCT01412333), supported the approval of Ocrevus for relapsing forms of MS. The trials tested the efficacy of Ocrevus in 1,656 patients, who were randomly assigned to Ocrevus (at the same dosage schedule used in ORATORIO) or Rebif (interferon beta-1a), a subcutaneous (under-the-skin) medication approved for relapsing MS. Treatment was given for 96 weeks (about two years).

Trial results showed that, compared with Rebif, Ocrevus’ use was associated with a 46% and 47% significant reduction in the annualized relapse rate in the two trials.

After two years, Ocrevus-treated patients also had 94% to 95% fewer new brain lesions on MRI scans, and significantly fewer patients on Ocrevus than Rebif experienced a confirmed worsening of disability (9.1% vs. 13.6%). This represented a 40% reduction in the risk of disability accumulation, which was also accompanied by a 33% higher rate of patients with a lessening in disability.

People who completed the randomized portion of the OPERA studies could enroll in an open-label extension, where all are being treated with Ocrevus and monitored for long-term safety and efficacy.

Data at 7.5 years showed that patients initially randomized to Ocrevus in the OPERA studies were 35% less likely to need a walking aid, compared with those who started on the treatment in the extension trial.

CHORDS and CASTING trials

A pair of Phase 3b clinical trials called CHORDS (NCT02637856) and CASTING (NCT02861014) tested Ocrevus in RRMS patients who had failed to adequately respond to treatment with other MS therapies. Each trial recruited more than 600 participants. They were generally similar, with some differences in eligibility criteria and other factors.

Results from CHORDS showed that, after two years of treatment, nearly half of patients showed no evidence of disease activity. In CASTING, nearly three-quarters of patients had no evidence of disease activity after about two years of treatment.

Ongoing trials

A number of clinical trials are currently ongoing in relapsing and progressive forms of MS.

O’HAND trial

One study, called O’HAND (NCT04035005), is testing Ocrevus against a placebo in approximately 1,000 adults with PPMS and at least moderate disability — including those who are confined to bed or a wheelchair but with generally effective use of their arms. The study aims to evaluate the treatment’s effect on upper limb function among these patients.

CONSONANCE trial

A Phase 3b trial called CONSONANCE (NCT03523858) is enrolling about 900 patients to investigate if Ocrevus can prevent disability progression in PPMS and SPMS patients with evidence of disability worsening in the absence of relapses. This group includes people with non-active SPMS, who have few available treatments.

ENSEMBLE trial

An ongoing Phase 3b clinical trial, ENSEMBLE (NCT03085810), is monitoring the safety and efficacy of Ocrevus in 678 people with early RRMS, or those with a disease duration shorter than three years and minimal to moderate disability. All are receiving treatment with Ocrevus.

Interim data from the trial showed that nearly 85% of these patients had no evidence of disease activity — meaning no relapses, disability progression, or worsening MRI measures — after one year of treatment.

CELLO trial

A planned Phase 4 trial called CELLO (NCT04877457) is designed to test whether a short course of Ocrevus can delay or prevent the onset of MS in people with radiologically isolated syndrome – individuals with MS-like brain lesions on MRI scans who don’t have any symptoms of the disease. A total of 100 patients will receive one year of treatment with Ocrevus or a placebo.

Common side effects of Ocrevus

The most common side effects associated with Ocrevus include the following:

• infusion reactions
• skin infections
• respiratory infections

Infusion reactions can include symptoms ranging from itching and a rash, a headache or dizziness, to trouble breathing or abnormal heartbeat patterns. These reactions occur mainly on the first infusion, and should be managed based on the particulars of the individual reaction. Should any patient have a life-threatening or disabling infusion reaction, treatment with Ocrevus should be permanently stopped.

Infection risk

Because Ocrevus suppresses the immune system, it can increase the risk of infections. Antibody levels should be measured before starting Ocrevus, and treatment should be delayed in patients with an active infection.

PML risk

A rare and life-threatening brain infection called progressive multifocal leukoencephalopathy (PML) has been described in some patients on Ocrevus.

Vaccines that contain a live virus should not be given to patients on the therapy.

Pregnancy risk

Well-controlled studies of Ocrevus during pregnancy or lactation are lacking, but animal data suggest that the medication can harm a developing fetus. It is recommended that patients who can become pregnant use contraception while on Ocrevus, and for at least six months after the last infusion. Those who become pregnant while on Ocrevus may enroll in a registry that is monitoring pregnancy outcomes with Ocrevus exposure.

Patients who plan to breastfeed should inform their healthcare provider, since research in animal models has found traces of Ocrevus in breast milk.

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