It is the first treatment that can slow the advancement of primary progressive MS. It can also treat relapsing MS.
What is ocrelizumab?
Ocrelizumab is an intravenous infusion treatment that has been developed by Hoffmann-La Roche.
Phase 3 clinical trial results for both primary progressive MS and relapsing MS were published in the New England Journal of Medicine on 22 December 2016.
Current phase of trial: Under review by European Medicines Agency (EMA) and US Food and Drug Administration (FDA)
Type of MS: primary progressive, relapsing remitting, and secondary progressive MS with relapses.
- How does ocrelizumab work?
- How is ocrelizumab taken?
- Latest research
- Earlier research
- What are the side effects of ocrelizumab?
- How does ocrelizumab compare with current therapies?
- When is ocrelizumab likely to become available?
Ocrelizumab is taken as an intravenous infusion every 6 months.
Two phase 3 trials (OPERA I and OPERA II) were completed in June 2015 and Roche reported positive outcomes for the effectiveness of ocrelizumab as a treatment for relapsing remitting MS against interferon beta-1a (also known as Rebif).
The trials involved over 1,600 people and after two years, the study is reported to show that ocrelizumab reduced the annual relapse rate by 46% in OPERA 1, 47% in OPERA II and the progression of clinical disability by 40%, as measured by the Expanded Disability Status Scale (EDSS).
The trial also found that around 50% of people taking ocrelizumab saw no evidence of disease activity (NEDA) in both OPERA I and OPERA II. This was compared with 25-30% of people taking interferon-beta-1a.
NEDA is defined as no relapses, no confirmed disability progression as measured by EDSS, and no new or enlarging lesions.
Primary Progressive MS
A phase 3 trial (ORATORIO) began in 2011 to test ocrelizumab against placebo in 732 people with primary progressive MS. This involved two infusions 14 days apart in each treatment cycle.
Results published in December showed that treatment with ocrelizumab reduced the risk of disability progression. The percentage of people with primary progressive MS that had disability progression (measured by EDSS) after 24 weeks fell from 36% without treatment to 30% with ocrelizumab.
Those taking the drug scored better on the time needed to walk 25 feet and ocrelizumab also reduced the rate of brain atrophy (shrinkage) shown on an MRI.
In 2008, a phase 2 clinical trial began testing ocrelizumab as a treatment for relapsing remitting MS against interferon beta-1a. 218 people were given either a low dose of ocrelizumab, a high dose of ocrelizumab, interferon beta-1a or a placebo drug.
After 24 weeks, the number of active lesions (as measured by MRI) was approximately 90 per cent lower in the ocrelizumab groups compared to the placebo group. People on both doses of ocrelizumab showed a lower frequency of relapses (70-80 per cent lower) compared with a placebo. People taking ocrelizumab also had significantly fewer relapses than those taking interferon beta-1a.
Some participants continued the trial for up to 96 weeks, in order to test the safety of long-term ocrelizumab treatment. In 2011, it was reported that the effects seen at 24 weeks were maintained at 96 weeks.
None of the phase 3 trials reported any unexpected adverse side effects. In ORATORIO, the incidence of side effects was similar to the placebo and in OPERA I and II, they were similar to those seen in the people taking interferon-beta-1a.
However, longer term studies are needed to understand the full safety profile of ocrelizumab. Weakening the immune system increases the risk of infection and of cancer emerging, and doctors have been advised to “stay vigilant”.
In the phase 2 relapsing remitting trial, serious side effects were rare and were comparable for all groups. One patient died in the high dose ocrelizumab group but it was unclear as to whether this was connected to ocrelizumab.
Ocrelizumab has also been investigated as a treatment for rheumatoid arthritis and lupus erythematosus, but studies were discontinued due to the number of infections that participants experienced.
The phase 3 trial of ocrelizumab as a treatment for relapsing remitting MS showed that ocrelizumab significantly reduced the annual relapse rate and the progression of clinical disability considerably when compared to interferon beta-1a treatment.
Roche have submitted the data from OPERA I, OPERA II and ORATORIO to the U.S. Food and Drug Administration (FDA) and ocrelizumab received Breakthrough Therapy Designation for primary progressive MS in February 2016. This means that the FDA should deliver its decision in March 2017.
In July 2016 Roche submitted a licensing application to the European Medicines Agency (EMA), the body responsible for licensing drugs in Europe. The EMA has accepted this application and is currently reviewing the data.
We expect a decision to be announced in late 2017.