Breaking News: OCREVUS™ (ocrelizumab) is the first drug approved by Health Canada for primary progressive MS
Breaking News (February 15, 2018): 1995 was a milestone year in Canada with the approval of the first disease-modifying therapy (DMT) for MS, specifically for relapsing-remitting MS. 2018 can be added to the list as another milestone year with the approval of the first DMT for primary progressive MS in Canada. Roche Canada announced the approval of Ocrevus™ (ocrelizumab), with conditions, for the treatment of people with early primary progressive MS (PPMS). Early PPMS will be defined by duration of disease and level of disability (measured using Expanded Disability Status Scale, EDSS). Ocrelizumab acts as an immunomodulatory drug by targeting and removing potentially harmful B cells (a type of white blood cell) in people living with MS. For more information on how ocrelizumab works, visit the disease-modifying therapies page and check out the ocrelizumab FAQ.
The approval was based on the efficacy and safety of ocrelizumab in a phase III clinical trial which was published by Montalban and colleagues. The trial, named ORATORIO, was a multi-centre, double-blind, randomized, placebo-controlled, Phase III clinical trial investigating the effectiveness of ocrelizumab in reducing clinical disability progression in people living with primary progressive MS. 732 participants with primary progressive MS, meeting the eligibility criteria which included age between 18 and 55 years, were enrolled in the trial.
Participants were randomly assigned in a 2:1 ratio to receive either ocrelizumab (via two intravenous infusions of 300mg given two weeks apart) or placebo, respectively. Treatment with ocrelizumab significantly reduced the proportion of individuals that experienced disability progression at 12 weeks compared with placebo (32.9% treated with ocrelizumab versus 39.3% with placebo), as measured by EDSS. Additionally, ocrelizumab significantly reduced the proportion of people that experienced disability progression at 24 weeks (29.6% on ocrelizumab compared to 35.7% with placebo).Ocrelizumab also outperformed placebo in a number of secondary endpoints. For example, at 120 weeks, 38.9% of individuals on ocrelizumab and 55.1% on placebo reduced in the time required to walk 25 feet (measured using the Timed 25-Foot Walk test). Other improvements with ocrelizumab were seen in imaging measures including a decrease in both lesion burden (number of new lesions) and brain volume loss.
The most common adverse events reported in the ocrelizumab treatment group in the ORATORIO trial were infusion-related reactions and infections (nasopharyngitis, urinary tract infections, influenza and upper respiratory track infections). Five deaths were reported in the ORATORIO trial, four of which were in the ocrelizumab group and included pulmonary embolism, pneumonia, and pancreatic cancer. One participant from the placebo group died as a result of a non-medical reason. In the open-label extension study of over 2,200 people with relapsing-remitting MS and primary progressive MS, the safety was consistent from previously reported results.
Ocrelizumab represents an important milestone in MS treatment as it provides further evidence of the role B cells play in MS. While ocrelizumab may be and an effective treatment for some people living with PPMS, more options are needed for people with progressive MS. The MS research community continues to focus on gaining a deeper understanding of the biological mechanisms underlying progressive MS.
Funding research in progressive MS continues to be a priority for the MS Society of Canada as the organization continues to be an active founding member of the international progressive alliance and funds numerous projects in the progressive MS area.