PellePharm readies hedgehog inhibitor for phase 3, plans series C after claiming success in small rare disease study

PellePharm pointed to a per protocol analysis of complete responses in its statement

PellePharm is gearing up for talks with the FDA about its phase 3 program. The biotech stepped up plans to get the late-stage study underway in the first half of next year after getting a look at data from a phase 2 trial of its hedgehog inhibitor in patients with Gorlin syndrome.

Investigators at two sites in the United Kingdom enrolled 17 patients with the rare genetic disease and randomized them to receive one of two doses of topical patidegib or placebo. The trial treated and tracked subjects for 26 weeks to assess the effect of twice-daily administrations of the hedgehog inhibitor on the basal cell carcinomas that characterize Gorlin syndrome.

PellePharm thinks the data support further development of patidegib but provided scant details in its top-line release. The primary clinical efficacy endpoint was “change from baseline in greatest diameter treatment-targeted surgically eligible basal cell carcinomas”. PellePharm’s release focuses on a statistically-significant difference in complete responses in the patidegib and placebo arms. 

The statistically significant result was achieved in a per protocol analysis, an approach that strips subjects that violate the protocol from the data. The approach is seen as not reflecting real-world results as well as intention-to-treat analyses. PellePharm pointed to the number of tumors that had complete responses in the patidegib arms, 12, and placebo cohort, zero, to bolster its case for the efficacy of the hedgehog inhibitor.

PellePharm’s release also refers to the trial’s primary measure of molecular efficacy, namely the reduction in hedgehog signaling pathway target gene GLI1. The biotech said complete responses correlated with a “meaningful” drop of the biomarker, suggesting a failure to achieve statistical significance against the molecular efficacy endpoint. 

Patidegib advanced into the clinic as a topical formulation after evidence accrued about the poor side effect profile of oral hedgehog inhibitors. No patients in the phase 2 trial suffered from the systemic side effects associated with the class of medicines. If replicated in a larger study that also clears the efficacy threshold, that safety performance would vindicate PellePharm’s decision to focus on a topical formulation.   

Management is now working toward the delivery of that data. In addition to talking to the FDA, PellePharm set to approach investors with a view to raising a series C round to fund phase 3. The biotech disclosed a third closing of its now $20 million series B alongside the top-line data. 

PellePharm licensed patidegib from Infinity Pharmaceuticals.