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
  • Emerging treatment for: RRMS and progressive MS
  • Status: In Phase III of clinical trials

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).

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 risk of progression of clinical disability sustained for at least 12 weeks by 24% compared with placebo, as measured by EDSS. Additionally, ocrelizumab was superior to placebo in a number of secondary endpoints. For example, it significantly reduced the risk of progression of clinical disability at 24 weeks by 25% and the time required to walk 25 feet (measured using the Timed 25-Foot Walk test) over 120 weeks by 29%. Ocrelizumab decreased the volume of T2 lesions by 3.4% over 120 weeks, compared to placebo which increased T2 volume by 7.4%. Ocrelizumab reduced the rate of whole brain volume loss over from week 24 to week 120 weeks by 17.5% compared to placebo. However, when participants were evaluated based on the Physical Component Summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey – which is designed to evaluate physical-health-related quality of life – there was no significant difference between those treated with ocrelizumab versus placebo.

Adverse Effects Reported

In clinical trials, serious adverse effects were reported to be rare. More people administered ocrelizumab had infusion-related adverse events compared to those in the placebo group at first infusion. Of note, one patient taking ocrelizumab (2000mg) died as a result of brain edema following a systemic inflammatory response with multi-organ failure. The connection between this death and ocrelizumab is unclear.

References

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