PXS-5505 Demonstrates Early Anti-Fibrotic Activity and Tolerability for Patients With R/R Myelofibrosis

PXS-5505 showed promising safety, tolerability, and early signs of anti-fibrotic efficacy in patients with relapsed/refractory (R/R) myelofibrosis (MF), according to results from a clinical trial published in Haematologica.  

The novel pan-lysyl oxidase inhibitor, PXS-5505 has previously shown antifibrotic qualities for patients with R/R MF. Researchers conducted a multicenter, phase 1/2a trial evaluating the safety and tolerability of PXS-5505 among patients refractory to Janus kinase inhibitor treatment with primary, post-polycythemia vera (PV) or post-essential thrombocythemia (ET) MF. The study included a dose escalation phase (DEP) and cohort expansion phase (CEP).

The primary outcomes were safety and tolerability. Secondary outcomes were pharmacokinetic (PK) and pharmacodynamic (PD) activity. Overall, 27 patients were included with 5 in the DEP and 24 in the CEP. The median age was 72 years, and most patients had post-ET MF (44%), followed by PMF (37%) and post-PV MF (19%).  

In the DEP, the highest tested dose of 200 mg BID without any dose limiting toxicities recorded. In terms of safety, 86% of adverse events were grade 1 or 2. In the CEP, 54% of patients completed 24 weeks of treatment and the median duration of treatment was 169 days (range, 16 to 191). Of 89 treatment emergent adverse events, 92% were determined to be not related to PXS-5505 treatment.

A total symptom score (TSS) reduction of ≥ 20% occurred in 62% of patients, with 15% achieving a ≥ 50% reduction. Approximately, 42% of patients demonstrated collagen fibrosis improvement and 33% demonstrated worsened collagen fibrosis by 1 grade.

"PXS-5505 is well-tolerated, with a distinct mode of action suitable for patient’s ineligible, relapsed or intolerant to JAK inhibitors,” the researchers concluded.

They added, “moreover, the pharmacological action and low propensity for drug-drug interactions make it an ideal candidate for use in combination with JAK inhibitors as well as other novel therapies."

“Overall, these data support continued investigation of PXS-5505,” they noted.

Source:

Vachhani P, Tan P, Watson AM, et al. A phase I / IIa trial of PXS-5505, a novel pan-lysyl oxidase inhibitor, in advanced myelofibrosis. Haematologica. Published online April 17, 2025. doi:10.3324/haematol.2024.287231