University of Western Australia’s Burn Injury Research Unit with the Fiona Wood Foundation reports that topical pan-lysyl oxidase inhibition with PXS-6302 was generally well tolerated over three months and altered extracellular matrix measures in mature scars.
Skin scars impose substantial burdens on appearance and psychological well-being. Lysyl oxidases catalyze collagen cross-linking that binds collagen strands tightly, increases mechanical strength, reduces collagen solubility, and makes tissue more resistant to degradation and turnover, with excessive cross-link formation associated with stiffness and fibrosis.
Current care for established scars often relies on revision surgery, laser treatment, or intralesional corticosteroid injections that can be painful, invasive, expensive, and inconsistently effective.
In the study, “A randomized, double-blind, placebo-controlled phase 1 trial of the topical pan-lysyl oxidase inhibitor PXS-6302 in mature scars,” published in Science Translational Medicine, researchers conducted a single-site Phase I randomized, double-blind, placebo-controlled trial to investigate safety and tolerability over three months, with secondary evaluations of pharmacokinetics and effects on the extracellular matrix and scar appearance.
Single-site enrollment at Fiona Stanley Hospital included 50 adults with established scars (?1 year old). Cohort 1 enrolled eight participants for open-label once-daily application of 2% PXS-6302 to a 10 cm2 scar area for three months. Cohort 2 included 42 participants randomized 1:1 to 2% PXS-6302 or placebo, dosed daily in week one, then three times per week for three months on a 10 cm2 area.
Participants applied cream via a microdosing device delivering 200 ?l per treatment (4 mg PXS-6302) to the target area. Scar biopsies were collected for lysyl oxidase activity, hydroxyproline, and total protein.
Safety outcomes showed no serious adverse events. Mild to moderate localized application-site reactions represented all treatment-related events and prompted discontinuation by six participants across cohorts. Laboratory values and vital signs showed no significant changes. Dosing frequency in cohort 2 shifted to three times per week after week one based on cohort 1 tolerability observations.
Scar tissue soaked up the cream while blood levels stayed minimal. Enzyme activity tied to collagen cross-linking dropped in treated areas with both dosing schedules, including by day 90.
Collagen-related signals moved downward with active treatment and upward with placebo. Biopsies showed lower hydroxyproline and lower total protein after three months with PXS-6302 compared with baseline and compared with placebo.
Optical scans on a subset revealed denser small blood vessels and higher tissue attenuation in treated scars by three months, with no vessel-density gain and a smaller attenuation rise in placebo.
Authors conclude that topical pan-lysyl oxidase inhibition achieved local enzymatic suppression with acceptable tolerability and measurable changes in extracellular matrix-related tissue metrics in mature scars, supporting advancement to Phase II trials with designs better powered and targeted to detect clinical improvements in appearance and texture.
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More information:
Natalie Morellini et al, A randomized, double-blind, placebo-controlled phase 1 trial of the topical pan–lysyl oxidase inhibitor PXS-6302 in mature scars, Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.adv2471
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