Efficacy and Safety of Sonidegib in Adult Patients with Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome): Results from a Phase 2, Double-Blind, Randomized Trial

John T Lear,¹ Axel Hauschild,² Eggert Stockfleth,³ Nicholas Squittieri,⁴ Nicole Basset-Seguin,⁵ Reinhard Dummer<sup>6

1</sup>Manchester Royal Infirmary, Manchester, UK; ²Klinik Für Dermatologie, Venerologie Und Allergologie Universitätsklinikum Schleswig-Holstein, Kiel, Germany; ³Universitätshautklinik Bochum, Bochum, Germany; ⁴Sun Pharmaceutical Industries, Inc., Princeton, NJ, USA; ⁵Department of Dermatology, Hôpital Saint Louis, Paris, France; ⁶Skin Cancer Center University Hospital, Zürich, Switzerland

Correspondence: John T Lear
University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK
Tel +44 161 276 4173
Fax +44 161 276 8881
Email john.lear@srft.nhs.uk

Nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin syndrome, is a rare hereditary disease characterized by the development of multiple cutaneous basal cell carcinomas (BCCs) from a young age.1 Loss-of-function germline mutations in the hedgehog-related patched 1 (PTCH1) tumor suppressor gene are the most common cause of NBCCS.¹ The hedgehog signaling pathway plays a major role in embryonic development, and in adulthood, is involved in the renewal and maintenance of distinct tissues, including hair follicles, muscle stem cells, and gastric epithelium.² Its abnormal activation is thought to drive the formation of both sporadic BCCs and those resulting from NBCCS.¹ Patients with NBCCS inherit one inactive copy of PTCH1 and then acquire a “second-hit” mutation, resulting in hedgehog pathway activation and BCC formation.¹ Mutations in Suppressor of fused (SUFU) or the PTCH1 homolog PTCH2 have also been found in a subset of patients meeting criteria for NBCCS.^1,3