Health Canada approves Ocrevus for RRMS


Ocrelizumab (Ocrevus) has now been approved for use in Canada for the treatment of adults with relapsing-remitting multiple sclerosis  with active disease defined by clinical and imaging features. An application was also submitted for use in primary-progressive MS, but has not yet received approval. The drug was approved by the U.S. Food and Drug Administration earlier this year (see FDA approves ocrelizumab in RRMS, PPMS, NeuroSens, March 30, 2017).

Ocrelizumab is a humanized monoclonal antibody that targets CD20, which is expressed primarily on B cells. B cells are rapidly depleted within two weeks of drug infusion, and remain depleted throughout the treatment course. In the phase II study, the median time to B cell repopulation (return to baseline or lower limit of normal) was 18 months; B cell counts returned to baseline/LLN in 90% of subjects by 2.5 years (Kappos et al. Lancet 2011;378:1779-1787).

Approval of ocrelizumab was based on the results of two phase III trials, OPERA I and OPERA II, in RRMS (Hauser et al. N Engl J Med 2017;376:221-234). In the two trials, 1,656 subjects with relapsing MS were randomized to ocrelizumab 600 mg by infusion every 24 weeks, or subcutaneous interferon-beta-1a 44 mcg three times per week, for 96 weeks. The annualized relapse rate was 0.16 with ocrelizumab versus 0.29 with the interferon (47% reduction). The mean number of gadolinium-enhancing T1 lesions was 95-97%% lower with ocrelizumab. In a pooled analysis, the proportion of patients with 12-week confirmed disability progression was significantly lower with ocrelizumab versus interferon (9.1% vs. 13.6%; the proportion with 24-week confirmed progression was 6.9% vs. 10.5%, respectively). For change from baseline in Multiple Sclerosis Functional Composite (MSFC) scores, which combines walking speed, upper-limb movements, and cognition, ocrelizumab was superior to interferon in OPERA II but not in OPERA I. The percent brain volume change (week 24-96) was significantly lower in OPERA 1 (-22.8% vs. IFN), but did not achieve significance in OPERA II.

The most common adverse event is infusion-related reactions (34.3%); subjects received IV steroids prior to infusion. There are also Warnings/Precautions about the risk of infections, notably respiratory tract infections; and herpesvirus infections, including herpes zoster (2.1% vs. IFN 1.0%), herpes simplex (0.7% vs. IFN 0.1%), oral herpes (3.0% vs. IFN 2.2%), genital herpes (0.1% vs. IFN 0%), and herpes virus infection (0.1% vs. IFN 0%).  There have been cases of hepatitis B reactivation, and patients should be screened for HBV infection prior to drug administration.

There may be an increased risk of malignancy with ocrelizumab, including breast cancer. According to the most recent safety update (5711 patient-years of exposure), the incidence rate of malignancy with ocrelizumab was 0.44 per 100 PY (Kappos et al. AAN 2017; P5.407). Patients are advised to follow standard breast cancer screening guidelines.

In contrast to the U.S. product label, the Canadian monograph includes a precaution about the use of ocrelizumab in patients with a history of depression or current depression: patients are advised to report symptoms of depression and/or suicidal ideation during treatment to their neurologist. In clinical trials, the incidence of depression was 8.5% with ocrelizumab vs. 7.9% with IFN.

Ocrevus is administered by IV infusion (300 mg two weeks apart for the first infusion, one 600 mg infusion thereafter). The infusion takes about 2.5 hours (300 mg) to 3.5 hours (600 mg); a one-hour observation period is advised. Pre-treatment with IV steroids, antihistamines and antipyretics may reduce the risk of infusion reactions.

Women of child-bearing potential should practice effective contraception until 6 months after the last dose of ocrelizumab. Ocrelizumab was excreted in breast milk in animal studies and women are advised not to breastfeed during treatment.

Click on the link to download the Canadian Product Monograph:

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