1. Academic Validation
  2. Pharmacokinetics and pharmacodynamics of itepekimab in healthy adults and patients with asthma: Phase I first-in-human and first-in-patient trials

Pharmacokinetics and pharmacodynamics of itepekimab in healthy adults and patients with asthma: Phase I first-in-human and first-in-patient trials

  • Clin Transl Sci. 2022 Feb;15(2):384-395. doi: 10.1111/cts.13157.
Matthew P Kosloski 1 George D Kalliolias 1 Christine R Xu 2 Sivan Harel 1 Ching-Ha Lai 1 Wenjun Zheng 1 John D Davis 1 Mohamed A Kamal 1
Affiliations

Affiliations

  • 1 Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
  • 2 Sanofi, Bridgewater, New Jersey, USA.
Abstract

Itepekimab is a monoclonal antibody that targets interleukin (IL-33) and has been shown to reduce airway inflammation and associated tissue damage in preclinical studies. We assessed the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamic profiles of single-ascending and multiple-ascending doses of itepekimab in two randomized, double-blind, placebo-controlled phase I studies. Healthy adults (N = 40) were randomized to the single-dose study and patients with moderate asthma (N = 23) to the multiple-dose study. Itepekimab was administered intravenously (0.3, 1, 3, or 10 mg/kg infusion) or subcutaneously (150 mg) in the single-dose study and subcutaneously (75 or 150 mg weekly for 4 weeks) in the multiple-dose study. Itepekimab exhibited linear PKs across studies and dose-proportional increases in mean maximum concentration in serum and area under the concentration-time curve following single intravenous or multiple subcutaneous doses. Itepekimab demonstrated mean subcutaneous bioavailability of 59-73% and a long terminal half-life (30.0-31.6 days). IL-33 concentrations in most healthy participants and patients with asthma were undetectable at baseline. Following administration of itepekimab in both studies, total IL-33 concentrations increased and blood eosinophils decreased, both with durable effect. Itepekimab was well-tolerated in both studies with no detection of treatment-emergent anti-drug antibody responses.

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