Multiple Sclerosis (MS)


Ocrevus (ocrelizumab) is a disease-modifying treatment for multiple sclerosis (MS) by Genentech, a member of the Roche group.1 

Ocrevus is the only disease-modifying treatment approved by the US Food and Drug Administration (FDA) to treat primary progressive multiple sclerosis (PPMS). The treatment is also approved for relapsing forms of the disease including clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (SPMS).2

The treatment is also authorized for use in the European Union to treat adult patients with relapsing forms of either MS or PPMS.3

Ocrevus treatment starts with 2 initial intravenous infusions of 300 mg each, given 2 weeks apart. This is followed by 600 mg infusions every 6 months.4

Mechanism of Action

Ocrevus is a humanized monoclonal antibody targeting CD20-positive B lymphocytes, which are involved in the immune attack against the myelin sheath in MS.1 

Get detailed prescribing information on the Ocrevus monograph page on Rare Disease Advisor.

The binding of Ocrevus to the CD20 protein expressed on the surface of B lymphocytes triggers antibody-dependent cellular cytolysis and complement-mediated lysis of these lymphocytes. This reduces their activity and the damage they cause to nerve cells, thereby relieving the symptoms of MS and slowing down disease progression. 

Warnings, Precautions, and Adverse Reactions

Ocrevus can cause serious side effects, including infusion reactions such as itching, rash, hives, tiredness, shortness of breath, fever, flushing, nausea, headache, dizziness, fatigue, and tachycardia.1 

It can also cause serious infections, including progressive multifocal leukoencephalopathy (PML) and hepatitis B virus (HBV) reactivation. Finally, Ocrevus may increase the risk of malignancies including breast cancer.

Patients with an active HBV infection should not be treated with Ocrevus. All patients should receive any required live or live-attenuated vaccines at least 1 month before starting Ocrevus treatment and should not receive any live or live-attenuated vaccines while being treated with Ocrevus.

It is not known whether Ocrevus harms the fetus. Patients are advised to use effective contraception while being treated with Ocrevus and for 6 months after the last Ocrevus infusion. It is also not known whether Ocrevus passes into breast milk.

Efficacy in Clinical Trials

The safety and efficacy of Ocrevus compared to Rebif® (interferon beta-1a) in patients with relapsing MS have been tested in 2 phase 3 clinical trials.5

OPERA TRIALS

The first trial, OPERA I, and the second trial, OPERA II, recruited 821 and 835 participants with MS aged 18 to 55 years, respectively. The primary endpoint of both randomized, double-blind, double-dummy, parallel-group studies was the annualized relapse rate at 96 weeks. Secondary outcome measures include time to onset of confirmed disability progression, the number of T1 gadolinium-enhancing lesions on magnetic resonance imaging (MRI), the number of new and/or enlarging T2 hyperintense lesions on MRI, and the percentage of participants with confirmed disability improvement.

Both trials are ongoing and are estimated to be completed in December 2023. Early results showed that the average annualized relapse rate in patients treated with Ocrevus was nearly 50% lower compared to that in patients treated with Rebif.3

ORATORIO

Another phase 3 study called ORATORIO is evaluating the safety and efficacy of Ocrevus treatment in patients with PPMS compared to placebo.6 The multicenter, randomized, parallel-group, double-blind, placebo-controlled study recruited 732 patients with PPMS aged 18 to 55 years. 

The primary endpoint of the study is the time to onset of clinical disability progression. Secondary outcome measures are the percent change in the timed 25-foot walk test, percent change in total volume of T2 lesions, percent change in total brain volume, change in physical component summary score in the SF-36 health survey, and the percentage of participants with at least 1 adverse event. 

ORATORIO is also ongoing with an estimated completion date of December 2023. 

Early results have shown that fewer patients treated with Ocrevus had worsening symptoms compared to those treated with placebo.3 Data also showed that early and continuous Ocrevus use can significantly slow the progression of disability in patients with PPMS and delay their need for a wheelchair.7

An exploratory analysis of data from all 3 clinical trials also showed that Ocrevus treatment reduced confirmed disability progression compared to Rebif or placebo.8

Cognitive Fatigue Trial

A more recent clinical trial seeks to examine the effects of Ocrevus on cognitive fatigue.9 The trial aims to enroll 60 participants with RRMS, age 18 to 64 years, who are going to be starting Ocrevus or Copaxone® (glatiramer acetate) treatment and matched healthy control groups. Cognitive fatigue that develops during the performance of a demanding task as well as how it changes as a function of treatment duration will be investigated during the trial.

References

  1. Ocrevus®: ocrelizumab. Genentech. Accessed June 15, 2021.
  2. Ocrevus. National Multiple Sclerosis Society. Accessed June 15, 2021.
  3. Ocrevus: ocrelizumab. European Medicines Agency. Updated May 18, 2021. Accessed June 15, 2021.
  4. Ocrevus dosage. Drugs.com. Updated March 24, 2021. Accessed June 15, 2021.
  5. A study of ocrelizumab in comparison with interferon beta-1a (Rebif) in participants with relapsing multiple sclerosis. ClinicalTrials.gov. November 24, 2010. Updated December 17, 2020. Accessed June 15, 2021.
  6. A study of ocrelizumab in participants with primary progressive multiple sclerosis. ClinicalTrials.gov. September 3, 2010. Updated December 17, 2020. Accessed June 15, 2021.
  7. Wolinsky JS, Arnold  DL, Brochet B, et al. Long-term follow-up from the ORATORIO trial of ocrelizumab for primary progressive multiple sclerosis: a post-hoc analysis from the ongoing open-label extension of the randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2020;19(12):998-1009. doi:10.1016/S1474-4422(20)30342-2
  8. Wolinsky JS, Engmann NJ, Pei J, Pradhan A, Markowitz C, Fox EJ. An exploratory analysis of the efficacy of ocrelizumab in patients with multiple sclerosis with increased disability. Mult Scler J Exp Transl Clin. 2020;6(1):2055217320911939. doi:10.1177/2055217320911939
  9. Examining effects of Ocrevus on cognitive fatigue using fMRI. ClinicalTrials.gov. June 26, 2020. Updated May 20, 2021. Accessed June 15, 2021.

Reviewed by Kyle Habet, MD, on 7/1/2021.

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