A phase 1 study evaluating the safety, tolerability, and pharmacokinetics of the porcupine inhibitor, AZD5055

Excessive Wnt signaling contributes to the development of fibrotic diseases and cancer. Here, we report the findings of a phase 1 study evaluating AZD5055, an orally administered porcupine inhibitor, which inhibits Wnt signaling. The primary objective was to evaluate the safety and tolerability of AZD5055 in healthy volunteers. Secondary and exploratory objectives were the pharmacokinetics and pharmacodynamics of AZD5055, respectively. Sixty healthy volunteers were randomized to receive placebo or AZD5055 in single ascending doses of 7, 20, or 40 mg (part 1), or multiple ascending doses of 5, 15, or 20 mg once daily over 14 consecutive days of dosing (Part 2). AZD5055 was safe and well tolerated in both study parts. AZD5055 exposure increased dose-proportionally with a pharmacokinetic profile enabling once daily dosing. AZD5055 effectively inhibited Wnt signaling in skin, hair follicles, and serum samples. Thus, AZD5055 has therapeutic potential in Wnt-driven fibrotic diseases and cancers.

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Publication Details

Journal
iScience
Published
2025-05-08
DOI
https://doi.org/10.1016/j.isci.2025.112602
Citations
2
Primary Topic
Liver physiology and pathology
Type
article
Field-Weighted Citation Impact
2.64

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article

A phase 1 study evaluating the safety, tolerability, and pharmacokinetics of the porcupine inhibitor, AZD5055

Xiaohong Zhou, Maria G. Belvisi, Zach Brohawn, Susanne Prothon et al.
2 citations
iScience
Liver physiology and pathology
2.64
article

A phase 1 study evaluating the safety, tolerability, and pharmacokinetics of the porcupine inhibitor, AZD5055

Xiaohong Zhou, Maria G. Belvisi, Zach Brohawn, Susanne Prothon, Caroline Ann Owen, Ronald Goldwater, Bernadette R. Gochuico, Michael L. Williams, Ellinor Hornberg, Christer Gottfridsson, Szilárd Nemes, J.O. Almquist, Adam Platt, Nicola Ferrari, Kebria Hezaveh, Olami Sobande, Zhi Liu, Engin Liathdale
article en
2 citations

Abstract

Excessive Wnt signaling contributes to the development of fibrotic diseases and cancer. Here, we report the findings of a phase 1 study evaluating AZD5055, an orally administered porcupine inhibitor, which inhibits Wnt signaling. The primary objective was to evaluate the safety and tolerability of AZD5055 in healthy volunteers. Secondary and exploratory objectives were the pharmacokinetics and pharmacodynamics of AZD5055, respectively. Sixty healthy volunteers were randomized to receive placebo or AZD5055 in single ascending doses of 7, 20, or 40 mg (part 1), or multiple ascending doses of 5, 15, or 20 mg once daily over 14 consecutive days of dosing (Part 2). AZD5055 was safe and well tolerated in both study parts. AZD5055 exposure increased dose-proportionally with a pharmacokinetic profile enabling once daily dosing. AZD5055 effectively inhibited Wnt signaling in skin, hair follicles, and serum samples. Thus, AZD5055 has therapeutic potential in Wnt-driven fibrotic diseases and cancers.

iScienceVol. 28(6)
MedStar Harbor Hospital (US), Lung Institute (US), AstraZeneca (Australia) (AU), AstraZeneca (Netherlands) (NL), AstraZeneca (Finland) (FI), AstraZeneca (Spain) (ES)
AstraZeneca
Zero hunger
Openalex Percentile: Top 11%
Liver physiology and pathology
2.64
DOIOpen Access PDFOpenAlex
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