The US Food and Drug Administration has approved ocrelizumab for the treatment of relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS); it is the first drug to target the progressive form of the disease.1
Marketed as Ocrevus™, the drug is potentially a major breakthrough in the treatment of MS, significantly reducing signs of disease activity in patients with RRMS2 and reducing relative risk of disability progression by 24% in some patients with PPMS.3
The drug, which is administered via intravenous infusion every 6 months, is the first MS therapy to target CD20-positive B cells instead of T cells, which are the target of currently available therapies.
Efficacy was established in 3 phase 3 trials: OPERA I and OPERA II for RRMS2 and ORATORIO for PPMS.3 In the OPERA studies, patients who were randomly assigned to receive ocrelizumab experienced a 46% and 47% reduction (in OPERA I and OPERA II, respectively) in annualized relapse rate over 2 years compared with patients who were given interferon beta-1a (P <.0001), as well as a 40% relative risk reduction in confirmed disability progression sustained for 12 weeks (P =.0006). Patients taking ocrelizumab also experienced a 94% and 95% reduction in each OPERA trial in the total number of T1 gadolinium-enhancing lesions and a 77% and 83% reduction in new and/or enlarging T2 lesions compared with patients receiving interferon beta-1a (all P <.0001).
In the ORATORIO trial, which included 732 patients with PPMS, treatment with ocrelizumab resulted in a 24% relative risk reduction in confirmed disability progression sustained for at least 12 weeks compared with placebo (P =.0321). Patients taking ocrelizumab also experienced a mean change of -0.39 cm3 in hyperintense T2 lesion volume compared with a mean 0.79 cm3 change in volume in patients taking placebo over 120 weeks (P <.0001). There was a 25% relative risk reduction in the proportion of patients who experienced a 20% worsening of the timed 25-foot walk test at 12 weeks.
The most common adverse effects observed in all phase 3 studies included infusion reactions and upper respiratory infections. Serious adverse effects associated with ocrelizumab include risk of progressive multifocal leukoencephalopathy, hepatitis B reactivation, and an increased risk of some malignancies, including breast cancer.
- FDA approves new drug to treat multiple sclerosis [news release]. US FDA newsroom; March 29, 2017. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm549325.htm
- Hauser SL, Bar-or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017; 376:221-234. doi: 10.1056/NEJMoa1601277
- Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017; 376:209-220. doi: 10.1056/NEJMoa1606468