Afamelanotide, sold under the brand name Scenesse, is a synthetic peptide and analogue of α-melanocyte stimulating hormone. It has been used to prevent skin damage from the sun in people with erythropoietic protoporphyria in the European Union since January 2015 and the United States since October 2019. As a medication, it is administered in subcutaneous implant form. Each implant lasts two months. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical use Afamelanotide is used in the European Union to prevent phototoxicity in adults with erythropoietic protoporphyria (EPP). Adverse effects Very common (may affect more than 10% of people) adverse effects in people with EPP include headache and nausea. Common (between 1% and 10%) adverse effects include back pain, upper respiratory tract infections, decreased appetite, migraine, dizziness, weakness, fatigue, lethargy, sleepiness, feeling hot, stomach pain, diarrhea, vomiting, flushing and red skin, development of warts, spots and freckles, itchy skin, and reactions at the injection site. There are many uncommon (less than 1%) adverse effects. Pharmacology Afamelanotide is thought to cause skin to darken by binding to the melanocortin 1 receptor which in turn drives melanogenesis. Afamelanotide has a half-life of 30 minutes. After the implant is injected, most of the drug is released within the first two days, with 90% released by the fifth day. By the tenth day no drug is detectable in plasma. Its metabolites, distribution, metabolism and excretion were not understood as of 2017. Chemistry The amino acid sequence is Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2. It is additionally known as [Nle4,D-Phe7]-α-MSH, which is sometimes abbreviated as NDP-MSH or NDP-α-MSH. Afamelanotide is the International Nonproprietary Name. History After the isolation and primary structure determination of a-MSH in the 1950s, many investigators initiated studies into the synthesis of this peptide. The role of α-MSH in promoting melanin diffusion has been known since the 1960s. In the 1980s, teams at the University of Arizona started to synthesise more potent analogs of a-MSH, including afamelanotide, which they initially named melano-tan (or melanotan-I) due to its ability to tan skin with minimal sun exposure, and later synthesised melanotan-II. Following initial development at the University of Arizona as a sunless tanning agent; the Australian company Clinuvel conducted further clinical trials in that and other indications, and brought the drug to market in the European Union, the United States, and Australia. To pursue the tanning agent, melanotan-I was licensed by Competitive Technologies,