Clinical stage drug developer Pharmaxis announced interim data from the clinical trial of its topical anti scarring drug PXS6302 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, known as SOLARIA2, is in 50 adult patients treated daily for scars of greater than one year in age and over 10cm2 in size for a period of 3 months. The first 8 patients treated were on active drug whereas the following 42 are being randomised 1:1 to active or placebo.

Preliminary results from open label phase with 8 patients treated for up to 3 months on active drug are: Skin punch biopsies taken 24 hrs after application at the end of the treatment period, show skin penetration and high inhibition of the lysyl oxidase enzymes that, based on preclinical 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 the second placebo controlled phase of the study, 24 out of the planned 42 patients have been recruited. In response to the adverse skin reaction 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. Final results are expected in H1 2023 when Pharmaxis 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.

In a separate development, UWA researchers last week published the preclinical studies performed in collaboration with Pharmaxis on topical treatment of skin scars with a pan LOX inhibitor that underpinned SOLARIA2. The preclinical studies, published in Nature Communications, clearly demonstrated that lysyl oxidase 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).

The preclinical data included in the publication were favourably reviewed by the FDA in preIND discussions with Pharmaxis where feedback was also useful in understanding potential endpoints of value in any regulatory process and the limitations of existing patient reported outcome measures. PXS6302 was discovered by the Pharmaxis research team at the company's Frenchs Forest laboratories. The project was supported by a National Health and Medical Research Council (NHMRC) development grant which funded extensive preclinical work executed in collaboration with UWA.

The ongoing clinical trial in patients with established scars and the planned follow up study will both be conducted at the Fiona Stanley Hospital in Perth with financial support from Pharmaxis.