In the United States, afamelanotide is indicated for increasing pain-free light exposure in adults with a history of reactions to light (phototoxicity) from erythropoietic protoporphyria.[1]
Afamelanotide is a synthetictridecapeptide and a structural analogue ofα-melanocyte stimulating hormone (α-MSH). It is a melanocortin receptoragonist and binds predominantly to theMC1 receptor. Its binding lasts longer than that of α-MSH. This results in part from afamelanotide's resistance to immediate degradation by serum or proteolytic enzymes. It is thought to cause skin darkening by binding to the MC1 receptor which in turn drivesmelanogenesis.[3]
It has a short half-life of approximately 30 minutes. After administration with implantation into the skin, the majority of the drug is released within two days, with 90% released by the fifth day. By the tenth day, no drug is detectable in plasma.[3]
Drug distribution, metabolism and excretion were not understood as of 2017.[3]
α-MSH was first isolated in the 1950s and its primary structure determined. By the 1960s, its role in promoting melanin diffusion was understood.[7]
In the 1980s, the University of Arizona synthesised more potent analogs of a-MSH, including afamelanotide. Afamelanotide was initially named melano-tan (or melanotan-I) due to its ability to tan skin with minimal sun exposure. Later,melanotan-II was synthesised.[8][9][10][11]
Following initialdevelopment at the University of Arizona as asunless 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, atechnology transfer company operating on behalf of University of Arizona, to an Australian startup called Epitan,[12][11] which changed its name to Clinuvel in 2006.[13]
Early clinical trials showed that the peptide had to be injected about ten times a day due to its short half-life, so the company collaborated withSouthern Research in the US to develop adepot formulation that would be injected under the skin, and release the peptide slowly. This was done by 2004.[12]
Multiple studies on the clinical effects of afamelanotide were conducted.[14][15] According toClinicalTrials.gov, Clinuvel sponsored several trials between 2007 and 2011 to explore its effects onerythropoietic protoporphyria,vitiligo,polymorphous light eruption,solar urticaria andacne vulgaris.[16][17][18] Additionally, one trial aimed to assess its role in preventingactinic keratosis in organ transplant recipients.[19] Further trials were pursued for the first two conditions, while results for the latter three were not published.[20][21][22] Following the initial trials, research efforts centered on erythropoietic protoporphyria, and due to theepidemiology of the condition. Clinuvel securedorphan drug for afamelanotide in both the US and the EU by 2010.[23]
The first approval of afamelanotide came in May 2010 from the Italian Medicines Agency (AIFA, or Agenzia Italiana del Farmaco), followed by theEuropean Medicines Agency (EMA) in January 2015. Both approvals were for the treatment of erythropoietic protoporphyria.[24][3]
The USFood and Drug Administration (FDA) granted approval in October 2019 for the use of afamelanotide as a medication to alleviate pain caused by sun exposure in individuals with erythropoietic protoporphyria. This decision was largely based on three trials involving 244 adults aged 18–74 across 22 sites in the US and Europe, which had a focus on pain-free hours in sunlight, outdoor hours under varying light conditions, and side effects.[4][25]
Between 2022 and 2023, trials were outlined to study the effects of afamelanotide onxeroderma pigmentosum andvariegate porphyria, along with two additional trials exploring its impact on vitiligo. According to theregister, as of April 2025, most of these trials are currently in the recruitment phase.
A number of products are sold online and in gyms and beauty salons as "melanotan" or "melanotan-1" which discuss afamelanotide in their marketing.[26][27][28]
Without a prescription, these drugs are not legally sold in many jurisdictions and are potentially dangerous.[29][30][31][32]
Starting in 2007, health agencies in various countries began issuing warnings against their use.[33][34][35][36][37][38]
^Habbema L, Halk AB, Neumann M, Bergman W (October 2017). "Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review".International Journal of Dermatology.56 (10):975–980.doi:10.1111/ijd.13585.PMID28266027.
^Langan EA, Nie Z, Rhodes LE (September 2010). "Melanotropic peptides: more than just 'Barbie drugs' and 'sun-tan jabs'?".The British Journal of Dermatology.163 (3):451–455.doi:10.1111/j.1365-2133.2010.09891.x.PMID20545686.
^Langan EA, Ramlogan D, Jamieson LA, Rhodes LE (January 2009). "Change in moles linked to use of unlicensed "sun tan jab"".BMJ.338: b277.doi:10.1136/bmj.b277.PMID19174439.S2CID27838904.
^"Legemiddelverket advarer mot bruk av Melanotan" [The Norwegian Medicines Agency warns against the use of Melanotan] (in Norwegian). Norwegian Medicines Agency. 13 December 2007.Archived from the original on 17 April 2009. Retrieved11 March 2009.
N
Y (what is this?) (verify)
This article incorporates text from this source, which is in thepublic domain.
