Sonidegib

Sonidegib is an oral hedgehog pathway inhibitor that targets the Smoothened (SMO) receptor. Marketed as Odomzo, it is approved for adults with locally advanced or metastatic basal cell carcinoma that is not amenable to surgery or radiotherapy.

Mechanism of action: By inhibiting SMO, sonidegib suppresses Hedgehog signaling and GLI transcription, reducing tumor cell proliferation and survival.

Administration: The recommended dose is 200 mg once daily, taken on an empty stomach.

Efficacy: In pivotal trials, sonidegib produced objective responses in locally advanced BCC and in some metastatic cases, with durability of responses varying among patients.

Safety: Common adverse events include muscle cramps or spasms, alopecia, dysgeusia (taste disturbance), fatigue, nausea, vomiting, diarrhea, and weight loss. Laboratory abnormalities may include elevated hepatic enzymes. Serious risks include myopathy, hepatic injury, and fetal toxicity; pregnancy must be avoided. Patients are monitored for liver function and other adverse effects, and contraception is required for those who could become pregnant.

Pharmacokinetics and interactions: Sonidegib is metabolized mainly by CYP3A4. Strong CYP3A4 inhibitors or inducers can alter exposure; avoid concomitant use or adjust therapy accordingly, with ongoing monitoring of liver function.

Regulatory status: Approved for use in adults with locally advanced or metastatic basal cell carcinoma in multiple regions, including the United States and the European Union. Resistance can arise through mutations in SMO or downstream components of the Hedgehog pathway.