Afamelanotide for the treatment of erythropoietic protoporphyria

Abstract

Introduction: Erythropoietic protoporphyria (EPP) is characterized by incapacitating pain in the sunlight-exposed skin areas due to accumulation of the metabolite protoporphyrin. Until now, no effective prevention of phototoxicity has been available. Afamelanotide, an α-melanocyte-stimulating hormone (α-MSH) analogue and first-in-class drug, induces melanin formation. The skin tan diminishes activation of protoporphyrin by reducing the sunlight penetration into the dermis. For continuous photoprotection, afamelanotide is applied every second month as a 16-mg controlled release implant.

Areas covered: In two Phase II and two Phase III trials in Europe, Australia and the US afamelanotide significantly reduced EPP-related phototoxic pain when tested in > 250 patients. To date, safety including compassionate use programs for up to 6 years appears to be excellent, including only nausea and flushing for a brief time after administration. No immunogenicity was observed. Approval for EPP treatment is pending at the European Medicines Agency.

Expert opinion: The authors assume that afamelanotide, being the first effective treatment of EPP, will be a broadly applied treatment of EPP in Europe, North America, Australia and likely also in other countries such as Japan, South Africa and South America within 5 years.

Keywords::

• afamelanotide
• erythropoietic protoporphyria
• first-in-class drug
• immunogenicity
• melanin induction
• melanocortin-one receptor
• Phase II and Phase III trials
• photodermatoses
• skin tanning
• α-MSH analogues