{"entity":{"id":"patidegib-gel-gorlin-phase-2","kind":"trial","name":"Patidegib gel in Gorlin syndrome (phase 2A)","aka":["patidegib topical gel phase 2A"],"tldr":"People born with Gorlin syndrome grow new basal cell carcinomas for life, and the pills that block the pathway cause side effects most cannot live with. Putting the drug on the skin instead was the obvious idea. A small trial hints that it works, but only in analyses decided after the results were seen.","summary":"Gorlin syndrome, caused by an inherited mutation in PTCH1, produces a continuous supply of new basal cell carcinomas, and is the human experiment that identified the hedgehog pathway as the driver of the sporadic disease too. Its sufferers are the people who would most benefit from long-term hedgehog inhibition and the people least able to tolerate it, since oral inhibitors have to be taken for years and their muscle spasms, taste loss and hair loss make that nearly impossible.\n\nPatidegib is a cyclopamine-derived inhibitor of smoothened formulated as a gel so that it reaches the skin without reaching the rest of the body. This small randomised double-blind phase 2A trial at two United Kingdom sites applied patidegib gel at 2 or 4 per cent, or vehicle, twice daily to the entire face for six months, and also to surgically eligible basal cell carcinomas at other sites.\n\nThe result must be stated with its qualification, which the paper itself supplies: post hoc analyses suggested that the gel reduced the number of new surgically eligible basal cell carcinomas and reduced the level of hedgehog signalling, with minimal adverse effects. Post hoc means the analyses were chosen after the data were seen, and seventeen participants cannot carry a pre-specified endpoint anyway. The authors conclude that the gel warrants further clinical development rather than that it works.\n\nThat is where the topical idea stands. A larger programme followed, including a phase 3 in Gorlin syndrome, and the record for it is on the basal cell carcinoma page. The reason to keep this small study is that it states the problem the whole class has: a drug that works and that people cannot take is not yet a treatment.","status":"mixed","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT02762084","url":"https://clinicaltrials.gov/study/NCT02762084"},{"label":"Phase 2A report (British Journal of Dermatology 2025)","url":"https://doi.org/10.1093/bjd/ljae444"},{"label":"Phase 2A report on PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/39545486/"}],"tags":[],"related":[],"cancers":["basal-cell-carcinoma","skin-cancer"],"sections":[],"technologies":["hedgehog-inhibitors"],"targets":["smoothened"],"drugs":["patidegib"],"companies":[],"institutions":[],"pathways":["hedgehog"],"terms":["hedgehog-inhibitor-tolerability"],"trials":["erivance","stevie"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02762084","phase":"2","setting":"Gorlin syndrome, in which an inherited PTCH1 mutation drives continuous formation of new basal cell carcinomas: patidegib topical gel at 2 or 4 per cent against vehicle, applied twice daily to the whole face for six months, with the number of new surgically eligible basal cell carcinomas and hedgehog pathway signalling as the endpoints","sponsor":"PellePharm, run at two United Kingdom sites","result":"Post hoc analyses in 17 participants suggested that patidegib topical gel reduced the number of new surgically eligible basal cell carcinomas and the level of hedgehog signalling, with minimal adverse effects; no pre-specified endpoint was met.","yearReported":2025,"enrolled":17,"enrolledBasis":"registry","outcomes":[{"endpoint":"New surgically eligible basal cell carcinomas over 6 months","primary":true,"unit":"post hoc analysis","arms":[{"name":"Patidegib topical gel 2 or 4 per cent","n":17,"note":"reduced against vehicle on post hoc analysis, with reduced hedgehog signalling and minimal adverse effects; the trial was not powered for a pre-specified endpoint"}],"source":"https://doi.org/10.1093/bjd/ljae444"}],"replication":"The phase 3 programme in Gorlin syndrome that followed is recorded on the basal cell carcinoma page as NCT06050122; no peer-reviewed phase 3 report of topical patidegib had been published when this record was written."},"route":"/trials/patidegib-gel-gorlin-phase-2/","neighbours":{"cancer":[{"id":"basal-cell-carcinoma","kind":"cancer","name":"Basal cell carcinoma","route":"/cancers/basal-cell-carcinoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"technology":[{"id":"hedgehog-inhibitors","kind":"technology","name":"Hedgehog pathway inhibitors","route":"/technologies/hedgehog-inhibitors/"}],"target":[{"id":"smoothened","kind":"target","name":"Smoothened (hedgehog pathway)","route":"/targets/smoothened/"}],"drug":[{"id":"patidegib","kind":"drug","name":"Patidegib","route":"/drugs/patidegib/"}],"pathway":[{"id":"hedgehog","kind":"pathway","name":"Hedgehog signalling","route":"/pathways/hedgehog/"}],"term":[{"id":"hedgehog-inhibitor-tolerability","kind":"term","name":"Why people stop taking hedgehog inhibitors","route":"/terms/hedgehog-inhibitor-tolerability/"}],"trial":[{"id":"nct06050122","kind":"trial","name":"Efficacy and Safety of Patidegib Gel 2% for Preventing Basal Cell Carcinomas on the Face of Adults With Gorlin Syndrome","route":"/trials/nct06050122/"},{"id":"erivance","kind":"trial","name":"ERIVANCE BCC","route":"/trials/erivance/"},{"id":"stevie","kind":"trial","name":"STEVIE (vismodegib in ordinary practice)","route":"/trials/stevie/"}]}}