Anti-Basal Cell Carcinoma Efficacy of a Topical Hedgehog Inhibitor Without Adverse Effects in Gorlin Syndrome Patients in a Phase 2 Randomized Controlled Trial

In a phase 2 randomized controlled trial, a topical hedgehog (HH) inhibitor, patidegib, was tested on patients with Gorlin syndrome to assess its efficacy in treating basal cell carcinoma (BCC) without causing the adverse effects associated with systemic HH inhibitors. The trial included 17 patients, with 5 using a vehicle gel, 6 using 2% patidegib gel, and 6 using 4% patidegib gel, applied twice daily to the face and target lesions. The 2% patidegib gel significantly reduced the size of surgically-eligible BCCs and completely cleared about 25% of them, with no complete disappearances in the vehicle group. Additionally, fewer new facial BCCs developed in the patidegib-treated groups compared to the vehicle group. The treatment's anti-BCC effect was linked to reduced HH pathway activity, and importantly, topical patidegib did not cause hair loss, taste loss, or muscle cramps, and had much lower circulating blood levels than oral HH inhibitors. This suggests that topical patidegib gel could potentially reduce or eliminate the need for surgeries in Gorlin syndrome patients without the adverse effects of current systemic treatments.