Multiple Sclerosis Society of Canada

Ocrelizumab



Overview:

  • Brand name: Ocrevus (Genentech/Roche)
  • Route of Administration: Two intravenous infusions of 300 mg given two weeks apart
  • Type: Humanized monoclonal antibody
  • Status: Submitted to Health Canada and approved by the U.S. FDA

Ocrelizumab is believed to influence the immune system response by binding to CD20 on the surface of B cells, leading to cell lysis (breaking down of a cell). Ocrelizumb is also being evaluated as an experimental treatment for relapsing forms of MS.

How it Works

Ocrelizumab is the humanized form of Rituximab, a mouse antibody to CD20 that has been met with some success in the treatment of RRMS. The humanized ocrelizumab is expected to be less immunogenic and therefore less likely to cause infusion reactions.

B cells are believed to be involved in the abnormal immune response in MS. Ocrelizumab is thought to influence the immune system response in MS through its involvement with B cells. Ocrelizumab binds to CD20, found on the surface of B cells, and causes cell lysis leading to a dose-dependent depletion of B cells.

Research and Results

The efficacy and safety of ocrelizumab for people living with primary progressive MS was evaluated in a phase III clinical trial and published by Montalban and colleagues. The trial, named ORATORIO, is a multicentre, double-blind, randomized, placebo-controlled, Phase III clinical trial designed to investigate the effectiveness of ocrelizumab in reducing clinical disability progression in people living with primary progressive MS. 732 participants with primary progressive MS were enrolled in the trial.

Participants were randomly assigned in a 2:1 ratio to receive either ocrelizumab (via 2 intravenous infusions of 300mg two weeks apart) or placebo, respectively. Treatment with ocrelizumab via 2 intravenous infusions of 300mg two weeks apart significantly reduced the proportion of individuals that experienced disability progression at 12 weeks compared with placebo (32.9% treated with ocrelizumab versus 39.3% with placebo), as measured by EDSS. Additionally, ocrelizumab significantly reduced the proportion of patients with disability progression at 24 weeks (29.6% on ocrelizumab compared to 35.7% with placebo). Ocrelizumab was also superior to placebo in a number of secondary endpoints. For example, at 120 weeks, 38.9% of individuals on ocrelizumab and 55.1% on the placebo had declined on the time required to walk 25 feet (measured using the Timed 25-Foot Walk test). Also, other improvements with ocrelizumab were seen in imaging measures like lesion volume and brain loss.

The U.S. Food and Drug Administration (FDA) approved ocrelizumab for the treatment of relapsing forms of MS (including secondary progressive MS with relapses) and primary progressive MS, based on the pivotal phase III data. The marketing application has been submitted to Health Canada for approval and is currently under review.

Adverse Effects Reported

The most common adverse events reported in the ocrelizumab treatment group in the ORATORIO trial were infusion-related reactions and infections (nasopharyngitis, urinary tract infections, influenza and upper respiratory track infections). Five deaths were reported in the ORATORIO trial, four of which were in the ocrelizumab group and included; pulmonary embolism, pneumonia, and pancreatic cancer. One participant from the placebo group died as a result of a non-medical reason.

References

Montalban X, et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med 2017; 376:209-220