Multiple Sclerosis Society of Canada

Ocrelizumab



Overview:

  • Brand name: Ocrevus (Genentech/Roche)
  • Route of Administration: Intravenous infusion (every 6 months)
  • 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 primary progressive 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

A phase II trialconducted by Dr. Ludwig Kappos and team was conducted in people with RRMS spanning 24 weeks. Participants received either placebo, low dose (600mg) ocrelizumab, high dose (2000mg) ocrelizumab, or interferon beta-1a treatment (an approved treatment for MS). At the end of the 24 weeks participants in both ocrelizumab groups had lower numbers of active brain lesions compared to the placebo group (89% lower in low dose ocrelizumab group and 96% lower in high dose ocrelizumab group). Both ocrelizumab groups were better than the interferon beta-1a group for reducing active lesions. Annualized relapse rates over the 24 weeks were 80% lower in the low dose ocrelizumab group and 73% lower in the high dose ocrelizumab group compared to the placebo group. Findings also showed that both doses of ocrelizumab were effective in reducing MRI and clinical disease activity.

Two phase III clinical trials were conducted by Dr. Stephen Hauser and team, OPERA I and OPERA II, to compare the effects of ocrelizumab (600mg every 24 weeks) compared to the already approved disease modifying therapy, interferon beta-1b (44 µg three times a week) for 96 weeks. Clinical outcomes from 1,656 participants enrolled in both trials show significantly reduced annualized relapse rates with ocrelizumab compared to interferon beta-1a at 2 years, thus meeting its primary endpoint. Secondary outcomes showed ocrelizumab had lower rate of disability progression at 24 weeks and fewer lesions.

The U.S. Food and Drug Administration (FDA) approved ocrelizumab for the treatment of relapsing 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 and is currently under review. For more information visit the ocrelizumab FAQ.

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

Kappos L et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011; 378 1779-87.

Hauser S et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017; 376 221-34.