title: Afamelanotide (CUV1647) in dermal phototoxicity of erythropoietic protoporphyria.
abstract: The application of afamelanotide, an α-melanocyte stimulating hormone agonistic analogue to protoporphyria, a disease with absolute sunlight-intolerance is discussed. The clinics, genetics and existing therapies of protoporphyria are described. The physiological receptor-mediated intracellular signaling of α-melanocyte stimulating hormone and effects of receptor variants are outlined. The pharmacological action of afamelanotide and the rationale behind its application in protoporphyria are given. The results of several Phase II and III and safety issues are discussed. The trial results were significant, although the effects were not very large in absolute terms, and the risk-safety profile is favorable today. Based on the high compliance rate and the excellent consistency in clinical effectiveness during six years of compassionate use program in Switzerland, we expect afamelanotide and analogues to become a prospective therapeutic tool. Moreover, we hope that dosage forms suitable for children will be developed in future, as children and adolescents suffer most in protoporphyria.
authors.affiliation: Institute of Laboratory Medicine, Stadtspital Triemli, CH-8063 Zürich, Switzerland.
authors.forename: Elisabeth I
authors.initials: EI
authors.lastname: Minder
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Schneider-Yin
mesh_terms: D000279:Administration, Cutaneous; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D046351:Protoporphyria, Erythropoietic / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D000521:alpha-MSH / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000521:alpha-MSH; C534526:afamelanotide
keywords: afamelanotide; clinical trials; orphan disease; protoporphyria; α-melanocyte stimulating hormone