Novel Aussie therapy shows promising anti-scarring effects

Cosmetic dermatology

By Michael Woodhead

27 Sep 2022

Prof Fiona Wood

An Australian company has released preliminary trial results showing its topical anti scarring drug PXS-6302  can modify scar tissue at a structural and biochemical level to improve cosmetic appearance.

Pharmaxis says its inhibitor of lysyl oxidase (LOX) enzymes developed at the University of WA has shown promise in a trial conducted by burns expert Professor Fiona Wood at the Fiona Stanley Hospital in Perth.

It said pre-clinical data published in Nature Communications (link here) showed that topical application of the pan-LOX inhibitor reduces collagen deposition and crosslinking and improve scar appearance without reducing tissue strength.

And interim data from the first eight of 50 patients treated with PXS-6302 has now shown a high level of inhibition of enzymes and changes in biomarkers that were implicated in scarring.

The trial, known as SOLARIA2, is being conducted by Professor Wood, Director of the Western Australia Burns Service, in 50 adult patients treated daily for scars of greater than one year in  age and over 10cm2  in size.

Results from the open label phase of the study with the first eight patients treated for up to three months on active drug showed skin  penetration and high inhibition of the lysyl oxidase enzymes.

Based on skin punch biopsies taken 24 hrs after application and at the end of the treatment period, showed reduction in the scarring biomarkers hydroxyproline and LOX, suggesting a normalisation of physiological  processes and a disease modifying effect.

“We have noted positive changes in appearance and pliability of scars in  those patients on active drug that now need to be confirmed by the results from the placebo controlled  phase of this trial later this year, said Prof Wood.

“We are learning a lot as we move from the promising preclinical work  done at UWA and into the clinic where we have many patients who are in great need of a treatment that  can improve both the cosmetic appearance of their scars and improve the functionality of their scarred  skin; factors that have a huge impact on patient’s wellbeing,”  she added.

However the study investigators noted that four patients withdrew from the study after experiencing redness and itching at the site of  application that resolved on treatment cessation.

In response to the adverse skin reactions seen with some patients in the unblinded active  phase, the treatment regimen has been reduced from once daily to three times a week application to reduce drug exposure whilst maintaining a high level of enzyme inhibition.

According to Pharmaxis, final results from the trial are expected in 2023, when it hopes to confirm an acceptable safety profile,  improvements in scar appearance and function for patients on active drug relative to those treated with  placebo, and evidence that LOX inhibition is modifying scar tissue at a structural and biochemical level.

Writing in Nature Communications, researchers at the UWA Burn Injury Research Unit, led by Dr Nutan Chaudhari, said the pre‐clinical studies with a pan LOX inhibitor in models of scleroderma, burn and hypertrophic scars supported the hypothesis that an agent which limits the extent of collagen crosslinking in the dermal extracellular matrix (ECM) during scar formation may enhance scar appearance and pliability.

“Lysyl oxidases are responsible for the oxidation of lysine side chain residues that spontaneously react to form crosslinks. These crosslinks render collagen and elastin less susceptible to degradation and this increased ECM stability promotes fibrosis,” they wrote.

“Our study shows that lysyl oxidase enzymes are expressed in scar tissue, supporting the development of a pan-LOX inhibitor to ameliorate scarring. Moreover, the development of a topically deliverable lysyl oxidase inhibitor in an easily applicable cream formulation overcomes the poor compliance of invasive therapies and the associated need for multiple hospital visits.”

Pharmaxis said PXS‐6302 was developed by a research team at the company’s Frenchs Forest laboratories in Sydney and the research was supported by an NHMRC development  grant in collaboration with UWA.

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