Higher exposure to Ocrevus (ocrelizumab) is associated with greater immune B-cell depletion in the blood, and lessened risk of disability progression in patients with relapsing multiple sclerosis (MS) and primary progressive disease (PPMS), according to new research.
The study supporting that finding, “Pharmacokinetics, Pharmacodynamics and Exposure-Response Analyses of Ocrelizumab in Patients With Multiple Sclerosis,” was presented at the 2019 American Academy of Neurology (AAN) Annual Meeting, held in Philadelphia May 4–10. The data were presented by Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco (UCSF).
Ocrevus is an approved treatment marketed by Genentech for patients with relapsing MS and those with PPMS. The therapy is a humanized monoclonal antibody that targets specific immune cells — CD20+ B-cells — and is administered intravenously (600 mg every six months).
In the study, researchers used Phase 2 and 3 clinical trial data to characterize Ocrevus’s pharmacokinetics — its absorption, distribution, metabolism, and excretion in the body — and pharmacodynamics (how the body responds to the therapy).
The team also analyzed exposure-response associations in terms of clinical effectiveness — as assessed through the annualized relapse rate, and 12- and 24-week confirmed disability progression (CDP) — and safety, namely the associated serious adverse side effects, serious infections, and infusion-related reactions.
Researchers created a model accounting for time-dependent Ocrevus’ clearance and patients’ body weight, which accurately described the treatment’s pharmacokinetics in 941 patients with relapsing MS and 482 with PPMS. Exposure to the therapy was 26% higher in patients with relapsing MS under 60 kilograms (kg), and 21% lower in those above 90 kg of body weight versus a 75 kg reference patient.
The data further showed that depletion of B-cells — targeted by Ocrevus — correlated with the extent of exposure to the therapy. Although the reduction in relapses was found to be independent of exposure in patients with relapsing MS.
Ocrevus also reduced lesions, assessed through magnetic resonance imaging (MRI), to nearly undetectable levels in relapsing MS and PPMS patients.
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