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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.
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.
Patidegib 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.
The 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.
That 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.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
17 enrolled.
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| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| New surgically eligible basal cell carcinomas over 6 monthsprimary | Patidegib topical gel 2 or 4 per cent | 17 | 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 | - | - | link |
Shares STEVIE (vismodegib in ordinary practice), Hedgehog pathway inhibitors, ERIVANCE BCC, Why people stop taking hedgehog inhibitors.
Shares STEVIE (vismodegib in ordinary practice), Hedgehog pathway inhibitors, ERIVANCE BCC, Why people stop taking hedgehog inhibitors.
Shares Patidegib, Hedgehog pathway inhibitors, Smoothened (hedgehog pathway), Hedgehog signalling.
Shares Patidegib, Hedgehog pathway inhibitors, Why people stop taking hedgehog inhibitors, Smoothened (hedgehog pathway).
Shares Patidegib, STEVIE (vismodegib in ordinary practice), Hedgehog pathway inhibitors, ERIVANCE BCC.
Shares STEVIE (vismodegib in ordinary practice), ERIVANCE BCC, Why people stop taking hedgehog inhibitors, Basal cell carcinoma.
Shares Efficacy and Safety of Patidegib Gel 2% for Preventing Basal Cell Carcinomas on the Face of Adults With Gorlin Syndrome, Patidegib, STEVIE (vismodegib in ordinary practice), Hedgehog pathway inhibitors.
Shares ERIVANCE BCC, Smoothened (hedgehog pathway), Hedgehog signalling, Basal cell carcinoma.