|Other names||[Nle4,D-Phe7]α-MSH; NDP-α-MSH; NDP-MSH; Melanotan; Melanotan-1; Melanotan I; EPT1647; CUV1647;|
|Drug class||MC1-R activator|
|Main uses||Erythropoietic protoporphyria|
|Side effects||Nausea, cough, tiredness, sleepiness, increased skin pigmentation, skin irritation|
|Elimination half-life||30 minutes|
|Chemical and physical data|
|Molar mass||1646.874 g·mol−1|
|3D model (JSmol)|
Afamelanotide, sold under the brand name Scenesse, is a medication used to prevent skin damage from the sun in erythropoietic protoporphyria. It increases the amount of light exposure before pain occurs. It is used as an implant under the skin.
Common side effects include nausea, cough, tiredness, sleepiness, increased skin pigmentation, and skin irritation. It should not be used in people with kidney or liver problems. Safety in pregnancy is unclear. It is a melanocortin 1 receptor (MC1-R) activator, which increases the amount of dark pigment produced by the skin.
Afamelanotide was approved for medical use in Europe in 2015 and the United States in 2019. As of 2022 it is not currently available in the United Kingdom. In the United States it costs 49,000 USD per implant as of 2022.
People who have severe liver impairment or kidney impairment, should not use this drug. Pregnant women should not take it, and women who are active sexually should use contraception while they are taking it. It is not known if afamelanotide is secreted in breast milk.
It is used as a 16 mg implant. This is done every two months during periods of high sunlight. Three to four implants per year may be used. It is an implant that is injected and placed under the skin; an implant lasts two months.
Very common (up to 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.
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.
The amino acid sequence is Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, and 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.
After the isolation and primary structure determination of a-MSH in the 1950s, many investigators initiated studies of 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, a technology transfer company operating on behalf of University of Arizona, to an Australian startup called Epitan, which changed its name to Clinuvel in 2006.
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 with Southern Research in the US to develop a depot formulation that would be injected under the skin, and release the peptide slowly. This was done by 2004.
As of 2010, afamelanotide was in Phase III trials for erythropoietic protoporphyria and polymorphous light eruption, and was in Phase II trials for actinic keratosis and squamous cell carcinoma, and had been trialled in phototoxicity associated with systemic photodynamic therapy and solar urticaria. Clinuvel had also obtained orphan drug status for afamelanotide in the US and the EU by that time.
There were three trials that evaluated afamelanotide in those with erythropoietic protoporphyria (EPP).
In Trial 1, subjects received afamelanotide or vehicle implant every two months and were followed for 180 days. Subjects recorded every day the number of hours spent in direct sunlight and whether they experienced any phototoxic pain that day. The trial measured the total number of hours over 180 days spent in direct sunlight between 10 am and 6 pm on days with no pain.
In Trial 2, subjects received afamelanotide or vehicle implants every two months and were followed for 270 days. Subjects recorded every day the number of hours spent outdoors whether “most of the day” was spent in direct sunlight, shade, or a combination of both, and whether they experienced any phototoxic pain that day. The trial measured the total number of hours over 270 days spent outdoors between 10 am and 3 pm on days with no pain for which “most of the day” was spent in direct sunlight.
In Trial 3 subjects were randomized to receive a total of three afamelanotide or vehicle implants administered subcutaneously every two months and were followed for 180 days. Data from this trial were used primarily for assessment of side effects.
The FDA approved afamelanotide based on evidence from three clinical trials (Trial 1/ NCT 01605136, Trial 2/ NCT00979745 and Trial 3/ NCT01097044) of 244 adults 18–74 years of age with EPP. The trials were conducted at 22 sites in the US and Europe.
In October 2019, afamelanotide was approved by the US Food and Drug Administration (FDA) as a medicine to reduce pain caused by light exposure (particularly sunlight) as experienced by sufferers of erythropoietic protoporphyria.
Society and culture
Unlicensed and untested powders sold as "melanotan" are found on the Internet marketed for tanning and other purposes, and multiple regulatory bodies have warned consumers that the peptides may be unsafe and ineffective.
It is under development in other skin disorders in several jurisdictions. It causes skin to turn darker by causing the skin to make more melanin.
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