Files and links (1)
CC BY-NC V4.0, Open Access
Journal article
A phase I / IIa trial of PXS-5505, a novel pan-lysyl oxidase inhibitor, in advanced myelofibrosis
Haematologica (Roma), Vol.110, pp.2376-2387
2025
PMID: 40241543
Abstract
Myelofibrosis (MF) is a progressive disease characterized by accumulation of extracellular matrix (ECM) in the bone marrow (BM) which impairs normal hematopoiesis. While Janus kinase (JAK) inhibitors reduce spleen volume and provide symptomatic improvement, they do not resolve BM fibrosis and may cause or exacerbate anemia and thrombocytopenia. An anti-fibrotic therapy capable of normalising BM microenvironment and function remains a significant gap in the current treatment landscape. MF is associated with elevated expression of lysyl oxidases; enzymes responsible for maturation of the most abundant ECM proteins, collagen and elastin. PXS-5505 is a novel pan-lysyl oxidase inhibitor designed to exert an anti-fibrotic mode of action by preventing the cross-linking of collagen and elastin. PXS5505-MF-101 is a multi-center phase 1/2a study of PXS-5505 in MF patients which included a dose escalation phase (DEP) and a cohort expansion phase (CEP). Primary objectives were to determine the safety and tolerability of PXS-5505 and to define dosing for future studies. The DEP demonstrated that the highest dose tested, 200 mg BID, was safe and achieved robust systemic reduction of lysyl oxidase activity; this dose was therefore selected for the CEP. Twentyfour patients (median age 72 years) with relapsed or refractory MF were recruited into the CEP and 54% (13/24) completed 24 weeks of treatment. PXS-5505 was well tolerated and reached steady state concentrations by Day 28. Over the 24-week treatment period preliminary indications of clinical efficacy, including a reduction in BM collagen, were evident. Overall, these data support continued investigation of PXS-5505.
Details
- Title
- A phase I / IIa trial of PXS-5505, a novel pan-lysyl oxidase inhibitor, in advanced myelofibrosis
- Authors/Creators
- Pankit Vachhani - University of Alabama at BirminghamPeter Tan - Linear Clinical ResearchAnne-Marie Watson - Liverpool HospitalShang-Ju Wu - National Taiwan University HospitalRoss Baker - Murdoch University, Centre for Molecular Medicine and Innovative TherapeuticsStanley Cheung - ICON Cancer Care, Kurralta ParkSung-Eun Lee - Catholic University of KoreaChih-Cheng Chen - Chang Gung Memorial HospitalTsai-Yun Chen - National Cheng Kung University HospitalHui-Hua Hsiao - Kaohsiung Medical UniversityJae Hoon Lee - Gachon University Gil Medical CenterLucia Masarova - The University of Texas MD Anderson Cancer CenterShuh Ying Tan - St Vincent's Hospital MelbourneJana Baskar - Syntara Limited, Frenchs Forest. jana.baskar@syntaratx.com.auBrett Charlton - Syntara Limited, Frenchs ForestAlison Findlay - Syntara Limited, Frenchs ForestDieter Hamprecht - Syntara Limited, Frenchs ForestWolfgang Jarolimek - Syntara Limited, Frenchs ForestJoanna Leadbetter - Syntara Limited, Frenchs ForestJohn Miller - Syntara Limited, Frenchs ForestKristen Morgan - Syntara Limited, Frenchs ForestAmna Zahoor - Syntara Limited, Frenchs ForestGabriela Hobbs - Massachusetts General Hospital
- Publication Details
- Haematologica (Roma), Vol.110, pp.2376-2387
- Publisher
- Ferrata Storti Foundation
- Identifiers
- 991005816849807891
- Copyright
- © 2025 Ferrata Storti Foundation
- Murdoch Affiliation
- Murdoch University; Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
Metrics
3 File views/ downloads
14 Record Views