Sonidegib

Sonidegib is an antitumor agent from the group of smoothened receptor antagonists (SMO inhibitor). The substance has antitumor and antiproliferative properties. Its effect is based on the inhibition of the Hedgehog signalling pathway by binding to the membrane protein Smoothened. This binding leads to reduced transcription of growth-promoting genes.

Sonidegib has a long half-life of 28 days.

Sonidegib is available for the treatment of inoperable or metastatic basal cell carcinoma. Approval was granted in a large phase II study with 230 patients (193 inoperable/37 metastatic basal cell carcinomas), in which 2 doses of 200 mg and 800mg/day p.o. were compared. After a 12-month follow-up period, the objective response rates were 91% for advanced local findings and 53% in the metastatic group.

The most common possible adverse effects include muscle cramps, muscle pain, hair loss, taste disorders, fatigue, indigestion, headache, pain and itching. Note: the side effects are similar to Vismodegib, they are obviously class specific.

Sonidegib is mainly metabolised by CYP3A4 and drug interactions are possible.

Sonidegib is contraindicated during pregnancy and lactation.

Odomzo®

1. Dummer R et al(2016) The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma. J Am Acad Dermatol 75:113-125.
2. Heppt M et al. (2016) What is new about basal cell carcinoma. Dermatologist 67: 876-883
3. Migden M.R. et al (2015) Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol 16, 716-728.
4. Rodon J. et al (2014) A phase I, multicenter, open-label, first-in-human, dose-escalation study of the oral smoothened inhibitor sonidegib (LDE225) in patients with advanced solid tumors. Clin Cancer Res 20, 1900-1909
5. Zollinger M. et al (2014). Absorption, distribution, metabolism, and excretion (ADME) of 14C-sonidegib (LDE225) in healthy volunteers Cancer chemother Pharmacol 74: 63-75.