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FDA Approves Ocrevus for Patients With Multiple Sclerosis

First medication for both relapsing and primary progressive forms of the disease

The FDA has greenlighted ocrelizumab (Ocrevus, Genentech) as the first medication for both relapsing and primary progressive forms of multiple sclerosis (RMS/PPMS). Most MS patients have RMS or PPMS at diagnosis.

Ocrelizumab is a humanized monoclonal antibody designed to selectively target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin and axonal damage. This nerve cell damage can lead to disability in patients with MS. Based on data from preclinical studies, ocrelizumab binds to CD20 cell-surface proteins expressed on certain B cells but not on stem cells or plasma cells, thereby preserving important functions of the immune system.

Ocrelizumab is administered by intravenous (IV) infusion every six months. The first dose is given as two 300-mg infusions administered two weeks apart. Subsequent doses are given as single 600-mg infusions.

The phase 3, global, randomized, double-blind, double-dummy OPERA I and OPERA II trials evaluated the efficacy and safety of ocrelizumab (600 mg administered by IV infusion every six months) compared with that of interferon (IFN) beta-1a (44 mcg administered by subcutaneous injection three times per week) in 1,656 subjects with RMS.

Key data showed:

  • A 46% and 47% relative reduction in the annualized relapse rate compared with IFN beta-1a during the two-year treatment period in OPERA I and OPERA II, respectively (P < 0.0001 for both trials)
  • A 40% relative risk reduction in confirmed disability progression (CDP) sustained for 12 weeks compared with IFN beta-1a in a pooled analysis of OPERA I and OPERA II, as measured by the Expanded Disability Status Scale (EDSS) (P = 0.0006).
  • A 94% and 95% relative reduction in the total number of T1 gadolinium-enhancing lesions compared with IFN beta-1a in OPERA I and OPERA II, respectively (P < 0.0001 for both trials)
  • A 77% and 83% relative reduction in the total number of new and/or enlarging T2 lesions compared with IFN beta-1a in OPERA I and OPERA II, respectively (P < 0.0001 for both trials)

The ORATORIO trial was a phase 3, global, randomized, double-blind study evaluating the efficacy and safety of ocrelizumab (600 mg administered by IV infusion every six months; given as two 300-mg infusions two weeks apart) compared with placebo in 732 subjects with PPMS. The blinded treatment period continued until all of the subjects had received at least 120 weeks of either ocrelizumab or placebo and until a predefined number of confirmed disability progression (CDP) events was reached.

Key findings included:

  • A 24% relative risk reduction in CDP sustained for at least 12 weeks compared with placebo, as measured by the EDSS (P = 0.0321)
  • A –0.39 cm3 mean change in the volume of brain hyperintense T2 lesions compared with a +0.79 cm3 mean change in volume in placebo-treated patients during 120 weeks of treatment (P < 0.0001)
  • A 25% relative risk reduction in the proportion of patients with 20% worsening of the timed 25-foot walk confirmed at 12 weeks.

The most common adverse events associated with ocrelizumab in all three studies included infusion reactions and upper respiratory-tract infections, which were mostly mild-to- moderate in severity.

The results from all three studies were published in the New England Journal of Medicine.

Source: Genentech; March 28, 2017.

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