Mechanism

Selective inhibition of Smoothened (SMO), a key transmembrane component of the hedgehog signalling pathway.
Constitutive hedgehog pathway activation drives BCC oncogenesis — most often via somatic PTCH1 loss-of-function mutations (which release SMO from PTCH1-mediated inhibition) or activating SMO mutations.
Sonidegib binds SMO and blocks downstream GLI transcription factors, halting BCC proliferation.
Active against the same molecular targets as vismodegib but with longer half-life and different metabolism (CYP3A4-dependent).

Evidence

BOLT trial (Migden et al., Lancet Oncol 2015; long-term follow-up 2017, 2020) — phase 2 RCT of sonidegib 200 mg vs 800 mg daily in 230 patients with laBCC or metastatic BCC.
- 200 mg arm — objective response rate 56% in laBCC at 30 months; durable responses; median PFS not reached in many; better tolerated than 800 mg.
- 800 mg arm — higher toxicity without improved efficacy; 200 mg established as the recommended dose.
Phase 2 mBCC subgroup — ORR ~ 8% but durable disease control in some.
No current positive NICE technology appraisal was identified for sonidegib in BCC on live NICE checking in May 2026.
No head-to-head trial vs vismodegib; comparable efficacy and toxicity profile.

200 mg orally once daily on an empty stomach (≥ 1 hour before or 2 hours after food).
Continue until disease progression, unacceptable toxicity or maximum benefit.
Long terminal half-life ~ 28 days — washout time longer than vismodegib for fertility and surgery considerations.
Teratogenicity / contraception: pregnancy testing before treatment. Female patients of reproductive potential must use effective contraception during treatment and for at least 20 months after the last dose; male patients with female partners should use condoms during treatment and for at least 8 months after the last dose (US label / prescribing information; confirm local UK product information at prescribing).
Dose interruption (treatment holidays) for tolerability — emerging UK practice supports drug holidays for muscle spasms / alopecia.
CYP3A4 substrate — avoid strong CYP3A4 inhibitors / inducers; review concomitant medications.

Muscle spasms — most common reason for discontinuation; lower limb predominantly; sometimes severe / painful.
Alopecia — diffuse hair loss usually starting after 1–3 months; partial recovery on cessation.
Dysgeusia / ageusia — significant impact on appetite and quality of life.
Weight loss — often substantial; nutritional support.
Fatigue, nausea, diarrhoea.
Amenorrhoea — often irreversible; pregnancy contraindicated (teratogenic).
CK elevation — monitor; rhabdomyolysis rare.
Reactivation of hidradenitis suppurativa, photosensitivity.
Cumulative toxicity often necessitates drug holiday / discontinuation at 6–12 months.

Same target (SMO) and class effects; comparable efficacy in laBCC.
Half-life — sonidegib ~ 28 days vs vismodegib ~ 12 days.
Fertility / pregnancy planning — sonidegib washout longer.
Patient preference, pharmacy availability, prior intolerance, drug interaction profile drive choice.
Cross-resistance between SMO inhibitors is recognised — limited benefit from switching for resistance.
Gorlin syndrome — both established options for multiple BCC; clinical trials of intermittent regimens ongoing.