Interim results from a phase IIb trial testing a proprietary formulation of the anti-fungal drug itraconazole for the treatment of Gorlin syndrome reduced tumor burden by more than 30 percent in eight of 13 patients, Hedgepath Pharmaceuticals Inc. reported.

Positive results at the conclusion of the study could lay the foundation for Hedgepath to file an FDA new drug application for the orphan-designated candidate, called SUBA-itraconazole. Approval to treat Gorlin syndrome, also known as basal cell carcinoma nevus syndrome (BCCNS), could then open the door to trials in lung and prostate cancers.

Patients with BCCNS, a condition tied to mutations in the PTCH1 gene, develop multiple basal cell carcinomas over time due to malfunctions in hedgehog signaling. The tumors are often removed with surgery, though locally advanced or metastatic basal cell carcinomas are sometimes treated with hedgehog pathway inhibitors, such as Genentech Inc.'s Erivedge (vismodegib) and Novartis AG's sonidegib. An estimated one in 40,000 people have BCCNS, according to the American Society of Clinical Oncology.

SUBA-itraconazole, which Hedgepath licensed from Mayne Pharma Ventures Pty Ltd., is also a hedgehog pathway inhibitor. But relative to Erivedge and sonidegib, it could potentially reduce lesion-burdens with fewer side effects than those drugs, Hedgepath CEO Nicholas Virca told BioWorld Today.

A phase II study of Erivedge in BCCNS patients, for instance, saw 20 percent of patients discontinue treatment due to adverse events. By comparison, Hedgepath found grade 1 or no toxicity reported in 90 percent of subjects assessed in its trial to date with no dropouts so far.

The data Hedgepath reported Wednesday were derived from an interim analysis of results in 13 participants who have completed 16 weeks of SUBA-itraconazole dosing during the ongoing open-label study. Each of the patients was enrolled in the trial with a requirement that the person exhibited significant basal cell carcinoma (BCC) target tumors at baseline consisting of a minimum of 10 surgically eligible lesions and had a history of surgical removal of at least 10 BCC tumors. For each subject, 10 to 15 of the largest lesions are selected by the investigator at baseline to represent a valid sample of overall lesions.

The study's primary endpoint is response rate of BCC lesions. None of the 13 participants included in the interim analysis saw target tumor burden grow during the study's 16-week dosing period and none had to have surgery to remove tumors. And tumor burden was reduced by more than 30 percent in eight of the patients, with an average reduction of 60 percent.

With respect to changes in the longest diameter of individual target lesions, a measure Hedgepath sees as addressing clinical utility, an interim analysis of 167 individual target lesions across all 13 subjects found that 25 percent of the cancerous lesions it tracked disappeared. An additional 25 percent exhibited greater than a 30 percent reduction, and 42 percent remained stable.

The overall average tumor reduction among responders has been "a promising" 75 percent, the company said. "Although 8 percent of target lesions analyzed in the interim data have increased by more than 20 percent in longest diameter, to date no primary tumors have required surgical intervention."

Hedgepath first became interested in the potential applications of itraconazole in cancer after research at Johns Hopkins University pointed to its application in the field. But, given the unmodified drug's relatively poor bioavailability and inconsistencies in blood plasma levels seen between patients after administration, it sought out delivery technologies to side-step those issues.

Their search yielded three potential solutions, out of which Virca and his partner, company chairman Francis O'Donnell, Jr. picked Mayne's SUBA technology. (SUBA stands for "super bioavailability.") "It's a polymer matrix that encapsulates itraconazole that protects it in the stomach, allowing it to pass all the way into the intestine where it's released under 5.0 pH," said Virca.

Since then, Melbourne, Australia-based Mayne, a subsidiary of Mayne Pharma Group Ltd., has become a principal stockholder in Hedgepath, owning 59.4 percent of its shares as of July 22. It also manufactures SUBA-itraconazole for Hedgepath, which currently has five full-time employees and 11 subcontractors.

The repurposing pathway, which puts Hedgepath on a path to 505(b)(2) approval given itraconazole's prior FDA approval in anti-fungal applications, lowers the company's regulatory risk. But the approach is also expected to keep the company's trial costs low, at about $3.5 million, said Virca. Pricing for SUBA-itraconazole could be about $5000 per month of therapy.

Hedgepath shares (OTCQB:HPPI) fell 5 cents, or 10 percent, to close at 45 cents on Wednesday.