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Updated: Jul 2, 2025
08:49
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
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Inhibition of Receptor-Interacting Protein Kinase 1 in Chronic Plaque Psoriasis: A Multicenter, Randomized,
Valerie J Ludbrook1, David C Budd2, Katie Thorn3
1Clinical Pharmacology and Experimental Medicine, GSK, Gunnels Wood Rd, Stevenage, Hertfordshire, SG1 2NY, UK. valerie.j.ludbrook@gsk.com.
Dermatology and Therapy
|February 19, 2024
Summary
The RIPK1 inhibitor GSK2982772 showed good tolerability in plaque psoriasis patients but did not significantly improve clinical outcomes compared to placebo. Further research into RIPK1 inhibition for psoriasis is warranted.
Area of Science:
- Immunodermatology
- Pharmacology
- Clinical Trials
Background:
- Receptor-interacting protein kinase 1 (RIPK1) is implicated in inflammatory diseases like psoriasis.
- Previous studies suggested potential efficacy of RIPK1 inhibition with improved drug concentrations.
Purpose of the Study:
- To evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of GSK2982772 in moderate to severe plaque psoriasis.
- To assess a modified-release formulation of GSK2982772 at a higher dose (960 mg once daily).
Main Methods:
- A 12-week, multicenter, randomized, double-blind, placebo-controlled study (NCT04316585).
- 29 patients with moderate to severe plaque psoriasis were randomized to GSK2982772 (N=19) or placebo (N=10).
- Assessed Psoriasis Area Severity Index (PASI) scores, safety, and pharmacodynamics.
Main Results:
- GSK2982772 was well tolerated, achieving higher trough concentrations than previous formulations.
- Near-complete RIPK1 target engagement and modest reductions in inflammatory cytokines were observed.
- No significant difference in PASI 75 response at week 12 between GSK2982772 and placebo groups.
Conclusions:
- GSK2982772 administration did not result in meaningful clinical improvements in patients with moderate to severe plaque psoriasis.
- Pharmacodynamic markers suggested local drug exposure, but this did not translate to clinical efficacy.
- The study did not support the use of this RIPK1 inhibitor for plaque psoriasis treatment.
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