First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis

Br J Clin Pharmacol. 2017 May;83(5):991-1001. doi: 10.1111/bcp.13185. Epub 2017 Jan 10.

Abstract

Aims: To assess safety, pharmacokinetics (PK) and clinical efficacy of bimekizumab (formerly UCB4940), a novel humanized monoclonal antibody and dual inhibitor of interleukin (IL)-17A and IL-17F, in subjects with mild plaque psoriasis.

Methods: Randomized, double-blind, first-in-human study of bimekizumab in 39 subjects who received single-dose intravenous bimekizumab (8-640 mg) or placebo (NCT02529956).

Results: Bimekizumab demonstrated dose-proportional linear PK and was tolerated across the dose range assessed. No subject discontinued due to treatment-emergent adverse events and no severe adverse events were reported. Bimekizumab demonstrated fast onset of clinically-meaningful effects on skin of patients with mild psoriasis as early as Week 2. Maximal improvements (100% or near 100% reductions from baseline) in all measures of disease activity were observed between Weeks 8-12 in subjects receiving 160-640 mg bimekizumab. The duration of effect at doses ≥160 mg was evident up to Weeks 12-20 after a single intravenous dose, dependent on endpoint.

Conclusions: This is the first study to demonstrate the safety, tolerability and clinical efficacy of a dual IL-17A and IL-17F inhibitor, in subjects with mild psoriasis. Bimekizumab showed fast onset of clinically-meaningful efficacy by Week 2, with a maximal or near-maximal magnitude of response that was maintained up to study Weeks 12-20. These findings support the continued clinical development of bimekizumab for diseases mediated by both IL-17A and IL-17F, including psoriasis.

Keywords: UCB4940; anti-IL17A; anti-IL17F; bimekizumab; interleukin-17; psoriasis.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Interleukin-17 / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Psoriasis / drug therapy*
  • Severity of Illness Index
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • IL17A protein, human
  • IL17F protein, human
  • Interleukin-17
  • bimekizumab

Associated data

  • ClinicalTrials.gov/NCT02529956