- How does it work?
- How is it given?
- What are the results so far?
- Side effects
- What further studies are planned?
|Drug in development|
|What is it for?||Relapsing remitting and primary progressive multiple sclerosis (MS)|
- Ocrelizumab is an experimental drug treatment for relapsing remitting and primary progressive MS. It is given as an intravenous infusion every 6 months.
- Ocrelizumab targets a marker (CD20) on the surface of B cells, which are thought to influence the abnormal immune response that causes the immune system to attack the myelin surrounding nerve.
- Preliminary results indicate that for relapsing remitting MS ocrelizumab is twice as effective as current disease modifying treatments.
- In clinical trials, serious side effects were rare and comparable in all treatment groups.
- One patient talking ocrelizumab died due to brain oedema (swelling), after the occurrence of systemic inflammatory response syndrome with multi-organ failure.
How does it work?
Ocrelizumab is a monoclonal antibody, a type of drug developed to attack specific targets in the immune system. Ocrelizumab has been designed to target a marker (CD20) on the surface of B cells, which are thought to influence the abnormal immune response that causes the immune system to attack the myelin surrounding nerve. The drug is a humanized version of rituximab, a mouse antibody to CD20 that has shown benefit in people with relapsing remitting MS.
Ocrelizumab has previously been investigated as a treatment for rheumatoid arthritis but studies were discontinued because of a high incidence of opportunistic infections in participants. Opportunistic infections are infections that do not normally occur in a healthy person but may occur when the immune system is compromised.
How is it given?
Ocrelizumab is given as an intravenous infusion every six months.
What are the results so far?
In a phase II, 24 week, clinical trial, 218 people were split into groups receiving one of two doses of ocrelizumab (600mg and 2000mg), interferon beta-1a (Avonex) or placebo. After 24 weeks, the number of active lesions as measured by MRI scans was 89% lower in the low dose group and 96% lower in the high dose group compared with the placebo group.
At 24 weeks the annual relapse rate was 0.13 in the low dose group and 0.17 in the high dose group compared to 0.36 for people on interferon beta and 0.64 in the placebo group.
In an extension to the study, participants were all switched to ocrelizumab treatment and reduction in relapses was maintained. Results from up to week 96 were reported at ECTRIMS 2011.
Opera I and II
In a press release, the manufacturer has announced completion of the Opera I and Opera II clinical trials.
These phase III studies recruited 1656 participants with relapsing remitting MS who took either ocrelizumab 600mg every 6 months or interferon beta 1a (Rebif) three times per week for approximately two years.
The press release reports that over the two years of the clinical trials, ocrelizumab was significantly better at reducing the number of relapses, significantly reduced increasing disability, and significantly reduced the number of lesions seen on MRI scans compared to beta interferon.
More details of Opera I and II will be presented at a scientific meeting.
Relapsing remitting MS
In the phase II RRMS study, serious side effects were rare and comparable in all four groups. However, one patient in the ocrelizumab 2000mg group died due to brain oedema (swelling), after the occurrence of systemic inflammatory response syndrome with multi-organ failure. The connection of this death to ocrelizumab is unclear.
At first infusion, more people in the ocrelizumab groups (35%, 44%) had infusion-related adverse events than did those in the placebo group (9%).
In preliminary results from the two phase III studies Opera I and Opera II, the most common side effects were mild to moderate infusion-related reactions. The incidence of serious adverse events associated with ocrelizumab, including serious infections, was similar to beta interferon.
What further studies are planned?
Primary progressive MS: Oratorio
This phase III study will recruit 630 participants with primary progressive MS. Treatment will be either 600mg ocrelizumab by iv infusion every 24 weeks or placebo, initially for 120 weeks (approximately 2 years). At the end of this period, participants who would be considered to benefit from continuing or switching to ocrelizumab treatment will be able to carry on with treatment for up to 5.5 years.
The main measure of the study will be the time taken to onset of sustained disability progression, defined as an increase in Expanded Disability Status Scale (EDSS) score that is sustained for at least 12 weeks.
The trial is due to finish in 2017.
Further details of Oratorio study.
Kappos L, et al.
Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial.