Pharmaxis Ltd (ASX:PXS, OTC:PMXSF) has demonstrated high levels of enzyme inhibition and changes in biomarkers implicated in skin scarring in interim data from a clinical trial assessing the use of topical anti-scarring drug PXS-6302.
The study is being conducted by the University of Western Australia (UWA) under the leadership of Professor Fiona Wood AM, director of the Western Australia Burns Service.
The trial – SOLARIA2 – will assess the efficacy of PXS-6302 in 50 adult patients treated daily for scars older than a year and larger than 10 square centimetres over a period of three months.
The first eight patients treated were on the active, open-label drug whereas the following 42 are being randomised 1:1 to active or placebo.
Results to be confirmed by second phase
“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,” Professor Fiona Wood said.
“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.”
Preliminary observations for the first eight patients treated in the open label phase include:
- Skin punch biopsies taken 24 hours after application at the end of the treatment period, show skin penetration and high inhibition of the lysyl oxidase (LOX) enzymes that, based on pre-clinical models, are fundamental to the scarring process.
- Reduction in the scarring biomarkers hydroxyproline and LOX was observed in the biopsies and based on preclinical models of the scarring process, suggests a normalisation of physiological processes and a disease-modifying effect.
- 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 reaction seen in some patients in the unblinded active phase, the company has opted to reduce the treatment regimen from one daily dose to three applications a week.
Preclinical studies on pan LOX inhibitor
In a separate but related development, researchers at UWA last week published pre-clinical studies assessing the topical treatment of skin scars with a pan LOX inhibitor that underpinned the SOLARIA2 treatment.
The preclinical studies – published in Nature Communications – demonstrated that lysyl oxidase (LOX) enzymes play a critical role in scar formation and maintenance by stabilising collagen, and driving scar stiffness and appearance.
The inhibition of these enzymes by Pharmaxis’ topically applied drug was shown to normalise collagen assembly and reduce fibrosis in different skin scar models (scleroderma, burn and hypertrophic scars).
Dr Mark Fear, senior research fellow at the Stan Perron Centre for Excellence in Childhood Burns, said: “In these scar models we found that topical application of PXS-6302 reduces collagen deposition and cross-linking and improves scar appearance without reducing tissue strength.
“This is a unique way of modulating a critical stage in scar formation and maintenance and holds out great promise for the treatment of scars.”
Data garners FDA favour
The preclinical data on Pharmaxis’ scarring treatment was favourably received by the US Federal Drug Administration (FDA) in pre-investigational new drug (IND) application discussions, which also generated useful information about potential endpoints of value in any regulatory process and the limitations of existing patient-reported outcome measures.
“The ongoing clinical study and our continued collaboration with Professor Wood and her team is providing us with a wealth of information,” Pharmaxis CEO Gary Phillips said.
“We will now work with UWA to design a follow-up study that will address the need for objective endpoints to meet anticipated regulatory hurdles and explore further indications that suit the profile of PXS-6302.”