According to an editorial, this is the first drug to show a significant effect in slowing disability progression in a phase 3 trial in primary progressive multiple sclerosis, and therefore the trial represents a landmark study in the field. It cautions however that side effects must also be considered such as susceptibility to infections and impaired immune surveillance of new cancer cells, which could increase the risk of neoplasms. It adds that to date, infection with JC virus causing progressive multifocal leukoencephalopathy, has not been seen with B-cell depletion in multiple sclerosis, but there does appear to be a higher-than-normal risk of herpes reactivation and of neoplasms, especially breast cancer. These side effects will need to be studied in future trials and in phase 4 monitoring in the community to understand the extent of the risk.
Also in the same journal, data from two RCTs (n=1656) in subjects with relapsing multiple sclerosis are presented. These found that annualised relapse rate was lower with ocrelizumab (OC) vs. interferon beta-1a (trial 1: 0.16 vs. 0.29; 46% lower rate with OC; p<0.001; trial 2: 0.16 vs. 0.29; 47% lower rate; p<0.001). Serious infection occurred in 1.3% on OC and 2.9% on interferon.
Ocrelizumab is an investigational, humanised monoclonal antibody designed to selectively target CD20-positive B cells, which are thought to be a key contributor to myelin and axonal damage.
A licensing application is currently sitting with the FDA who has extended the review period due to submission of additional data by Genentech regarding the commercial manufacturing process of the drug.