Conference Coverage

Patidegib, the first topical hedgehog inhibitor, scores in Gorlin syndrome



Patidegib, a first-in-class topical hedgehog pathway inhibitor, mitigated the burden of facial basal cell carcinoma in patients with Gorlin Syndrome in a phase 2 study, and did so without causing the problematic adverse events that prompt many Gorlin patients to discontinue systemic hedgehog inhibitor drugs, Ervin Epstein Jr., MD, said at the annual meeting of the American College of Mohs Surgery.

He characterized patidegib, a small-molecule cyclopamine derivative, as “a Goldilocks drug, a topical hedgehog inhibitor with percutaneous absorption that’s just right: sufficient to have anti-hedgehog and anti–basal cell carcinoma efficacy, but not enough to cause systemic exposure or systemic adverse events.”

Dr. Ervin Epstein Jr., cofounder and chief medical officer at PellePharm, based in Menlo Park, Calif. Bruce Jancin/MDedge News

Dr. Ervin Epstein Jr.

He presented the results of a double-blind phase 2 proof-of-concept study conducted in the United Kingdom. It involved 18 patients with Gorlin syndrome and, collectively, 68 surgically eligible basal cell carcinomas (BCCs) on the face at baseline; patients were randomized to application of 2% or 4% patidegib gel or vehicle twice daily all over their face for 6 months.

A complete response – tumor clinical disappearance – occurred in 25% of the BCCs in the two active treatment arms. In contrast, none of the BCCs in the control group cleared. Patients on patidegib developed one or more new surgically eligible BCCs after study week 2 at a rate of 0.4 tumors per patient, markedly less than the rate of 1.4 tumors per patient in controls.

“We think that prevention is really the place to go with this drug,” said Dr. Epstein, cofounder and chief medical officer at PellePharm, the company based in Menlo Park, Calif., that is developing patidegib.

Indeed, he envisions patidegib gel as lifetime therapy for Gorlin patients.

Tumor shrinkage was significantly greater with 2% patidegib than with the 4% concentration. But so was treatment adherence: Patients in the 2% patidegib arm missed on average just 2 days of therapy over the course of 6 months, while those in the 4% arm missed 50 days. Dr. Epstein attributed this discrepancy to a freak of randomization that can occur in such a small study: 5 of 6 patients in the 2% patidegib group were women, while most in the 4% arm were men. And the men were far less adherent to treatment, possibly because men are less accustomed to applying a product on their face daily, he noted.


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