What it is
Melanotan I is a lab-made copy of a hormone called α-MSH. This small hormone tells pigment cells in the skin to make melanin. Melanin is the dark pigment that colours skin. The natural hormone breaks down fast. Scientists changed two of its building blocks. The new version lasts much longer and works much more strongly.
Its official drug name is afamelanotide. Only one product is approved. It is called Scenesse. It is a tiny rod placed under the skin of the hip every two months. It is approved for people with erythropoietic protoporphyria (EPP). EPP is a rare condition that runs in families. In EPP, light on the skin causes severe burning pain. Darker skin is thought to block some of that light.
Powders for injection and nasal sprays are sold online as “Melanotan I” for tanning. These are not Scenesse. They are not approved anywhere.
Afamelanotide is [Nle4, D-Phe7]-α-MSH, a linear tridecapeptide amide (C78H111N21O19, 1646.8 g/mol free base). Replacing Met4 with norleucine removes an oxidation-prone residue, and D-phenylalanine at position 7 is thought to stabilise a β-turn in the His-Phe-Arg-Trp core; the 1980 paper reported resistance to serum enzymes. The result is a melanocortin receptor agonist that binds predominantly to MC1R on melanocytes. MC1R is a Gs-coupled receptor; activation raises cAMP and shifts melanogenesis toward eumelanin, which the label describes as occurring independently of UV exposure.
Scenesse is a controlled-release implant of 16 mg afamelanotide in a poly(DL-lactide-co-glycolide) rod. In 12 healthy adults the label reports high variability, a median Tmax of 36 hours, mean Cmax 3.7 ng/mL, an apparent half-life of about 15 hours, and plasma levels measurable to about 96 hours in most subjects. The pigmentary effect outlasts plasma exposure, which is why dosing is every two months. Metabolism is presumed to be hydrolytic and has not been fully characterised.
Who made it and when
The drug was made at the University of Arizona in Tucson. In 1980, chemist Victor Hruby, biologist Mac Hadley and their team shared a finding. Swapping two amino acids (building blocks) in α-MSH made it much stronger. It also made it last much longer. Other Arizona researchers, including Norman Levine and Robert Dorr, then tested it in people. They wanted a way to tan without sun. It later became known as Melanotan I.
An Australian company called EpiTan took a licence to the drug. The company later changed its name to Clinuvel. Clinuvel stopped aiming the drug at cosmetic tanning. It focused instead on rare conditions where light harms the skin. Europe allowed Scenesse in December 2014. The US FDA approved it on 8 October 2019. Australia’s drug regulator followed in October 2020.
Sawyer, Sanfilippo, Hruby, Hadley and colleagues described [Nle4, D-Phe7]-α-MSH in PNAS in 1980, reporting 26-fold greater potency than α-MSH in an adenylate cyclase assay and resistance to serum enzymes. Levine et al. (JAMA 1991) ran a randomised, double-blind, placebo-controlled trial in 28 healthy men showing skin darkening after 10 subcutaneous injections over 12 days, while subjects used a high-potency sunscreen. The name Melanotan II was later given to a separate cyclic analogue from the same group.
Development rights were licensed in 1999 to the Australian company EpiTan, which changed its name to Clinuvel Pharmaceuticals in 2006 (Clinuvel annual report 2006). The EU marketing authorisation (December 2014) was granted under exceptional circumstances because the rarity of EPP limited the data that could be collected. FDA approved NDA 210797 on 8 October 2019 as a new molecular entity. An EU application to extend use to adolescents was withdrawn by the company on 24 April 2024. No compound patent could be verified for this article, so none is listed.
What the data say
Approval was based on two trials in people with EPP. Both were published in 2015. In both, some people got a dummy treatment (placebo) to compare against. In the US trial, people with the implant spent a middle value of about 69 hours in direct sun without pain. That was over six months. People on the placebo spent about 41 hours. In the European trial, the gap in hours was smaller. But the implant group had about half as many painful reactions. Scores for quality of life got better.
The most common side effects were:
- a reaction where the implant goes in
- feeling sick to the stomach (nausea)
- darker skin and darker moles
A large trial is testing the drug in vitiligo. Vitiligo is a condition where patches of skin lose their colour. The trial finished signing up people in 2025. It had not shared results when this was written. The company has said it expects first results in December 2026.
Newer reports add to the picture. In Austria, all 20 people with EPP treated in 2023 were followed. Their quality-of-life score rose from 11 to 79 out of 100, and the time they could spend in sunlight before a burn rose from 15 to 250 minutes. A study of 28 people aged 12 to 70 with EPP tested a single implant. No one had a serious side effect, but 23 of 28 had some side effect, most often headache or nausea.
Langendonk et al. (NEJM 2015) reported two randomised, double-blind, placebo-controlled trials of 16 mg implants every 60 days. CUV039 (US, n=94 randomised) reported median pain-free direct-sunlight time of 69.4 vs 40.8 hours at 6 months (P=0.04); the label reports 64.1 vs 40.5 hours for the same 10 am–6 pm window. CUV029 (EU, n=74, five implants over 270 days) reported 6.0 vs 0.8 hours (P=0.005) and 77 vs 146 phototoxic reactions (P=0.04). Serious adverse events were not considered drug-related.
Across 244 EPP subjects in three vehicle-controlled studies, the label lists implant-site reactions (21% vs 10%), nausea (19% vs 14%), skin hyperpigmentation (4% vs 0%) and melanocytic naevus (4% vs 2%). CUV105 (NCT06109649), an open-label Phase 3 trial of afamelanotide every 3 weeks plus narrowband UVB versus UVB alone in generalised vitiligo (Fitzpatrick skin types III–VI), is active but not recruiting; Clinuvel’s July 2026 SEC filing reported 210 patients enrolled and topline results expected in December 2026. The same 28 July 2026 company release states that the EMA reviewed the protocol of a pivotal vitiligo study, CUV107, in April 2026, planned for 300 patients with Fitzpatrick skin types IV–VI and a November 2026 start with 12 months of recruitment (company statement). Published case reports link unregulated “melanotan” injections, often of uncertain identity, to changing or new naevi and a small number of melanomas; those reports concern unapproved products, not Scenesse. Ume et al. (Clin Exp Dermatol 2026;51:1971-1974, PMID 42212476) add a 47-year-old man who self-injected an unverified online product described as “melanotan I (afamelanotide)” 2 mL subcutaneously daily for about 1.5 months and developed vitiligo-like depigmented patches on the neck, jaw and cheeks, with partial repigmentation after stopping.
Newer data on the approved implant: NCT06388642 (Phase 1/2, n=28, ages 12–70, single 16 mg implant; results posted 2026-07-27) reported geometric-mean Cmax 2.361 ng/mL and AUC0–inf 114.406 h·ng/mL, no serious adverse events and any adverse event in 23 of 28 (headache 6, nausea 4, influenza-like illness 4, diarrhoea 3, rhinitis 3, photosensitivity reaction 3, implant-site haematoma 2); the registry’s age bands indicate adolescents were included, making this the first exposure data in that age group. Griffin et al. (Photochem Photobiol Sci 2026;25:2223-2230, PMID 42678656) gave 9 healthy volunteers (phototypes II–III) a single 16 mg implant: six days later the UVR-erythema dose-response AUC fell from 3.5 to 2.7 (P=0.018), the MED rose from a median 21 to 29.9 mJ/cm² (not significant) and melanin density rose 2.4–2.9% (P=0.001). Seidl-Philipp et al. (J Dtsch Dermatol Ges 2026, PMID 41793078) reported all 20 Austrian EPP patients treated in 2023: median EPP-QoL 11.11 to 79.17, phototoxic burn tolerance 15 to 250 minutes, patients with phototoxic reactions 88% to 33%, side effects only mild and transient. Minder and Barman-Aksözen (JAAD Case Rep 2026;68:6-8, PMID 41542313) describe an off-label single 16 mg implant in a 9-year-old girl with EPP (EPP-QoL 0 to 55.6 at 5 weeks, mild nausea for a couple of days); the label still states that paediatric safety and effectiveness have not been established.
Regulatory picture
There are three separate points here.
Approval: The FDA approved afamelanotide as Scenesse. But it is approved only for adults with EPP. It is only approved as an implant put in by a trained professional. It is not approved for tanning, vitiligo or any other use.
Pharmacy-made versions: An approved product exists. So pharmacies may not make copies of it. A US pharmacy may still legally use it as an ingredient in a mix made for one patient, if the mix is not a copy. The FDA does not review these mixes.
Enforcement: No FDA warning letters naming Melanotan I by name were found. The powders and sprays sold online as “Melanotan I” are not approved. No one knows for sure what is in them. Australia’s drug regulator (TGA) has warned the public against melanotan tanning products. The UK’s drug regulator (MHRA) says it has removed melanotan products from sale many times.
Approval: approved. NDA 210797 (Clinuvel), approved 2019-10-08 for increasing pain-free light exposure in adults with a history of phototoxic reactions from EPP; the latest label revision (08/2024) lists a new contraindication for severe hypersensitivity. Clinuvel announced on 27 April 2026 that FDA had determined a postmarketing QT study “was no longer needed as it would not provide useful safety information”, and that no REMS was ever required; this comes from the company’s ASX announcement, not an FDA document. The EU authorisation dates from December 2014 and the TGA registration from October 2020.
Compounding: recorded as restricted, meaning copies of Scenesse are not permitted. Because afamelanotide is a component of an FDA-approved drug, section 503A allows it as a bulk ingredient for patient-specific preparations that are not essentially copies; such preparations are not FDA-reviewed. It is not among the peptides FDA placed in Category 2 in 2023. Unapproved injectable or intranasal “Melanotan I” products fall outside both the NDA and any compounding pathway.
International: Australia’s TGA warned in January 2025 that tanning products labelled Melanotan I or II are illegal to supply without a prescription, and the UK’s MHRA stated in a 2021 freedom-of-information response that it had repeatedly acted to remove melanotan products from sale for over 10 years. Habbema et al. (2017) note that multiple national health organisations have issued warnings on melanotan I and II. Those warnings concern unlicensed products, not Scenesse.
