Melanotan I (afamelanotide, Scenesse)

Summary

Melanotan I is the original alpha-MSH analog, now the FDA approved drug afamelanotide (Scenesse), a 16 mg subcutaneous implant approved in October 2019 to increase pain-free light exposure in adults with the rare photosensitivity disorder erythropoietic protoporphyria. In two randomized placebo-controlled trials it increased median pain-free direct sunlight exposure from 40.8 to 69.4 hours over 6 months (US, n = 94) and from 0.8 to 6.0 hours over 9 months (EU, n = 74), with mostly mild adverse events. It is available only through specialist centers and is not approved or lawfully sold for cosmetic tanning; the injectable Melanotan I sold online is an unapproved product.

What is Melanotan I (afamelanotide)?

Melanotan I (afamelanotide) is a synthetic linear 13 amino acid analog of alpha-melanocyte stimulating hormone, selective MC1R agonist, delivered as a subcutaneous implant. It is also known as Afamelanotide, Scenesse, MT-I, MT1, [Nle4, D-Phe7]-alpha-MSH, CUV1647, Melanotan 1, Melanotan-1, MT-1.

How does it work?

Afamelanotide is a potent, long acting agonist at the melanocortin 1 receptor on melanocytes. MC1R activation increases eumelanin production and melanocyte proliferation, which darkens skin and provides a photoprotective pigment barrier without UV exposure; it also has anti-inflammatory and antioxidant effects in skin cells. Unlike Melanotan II it has little activity at MC3R and MC4R, so it does not meaningfully affect sexual function or appetite.

What does the evidence say about Melanotan I (afamelanotide)?

Two multicenter randomized, double-blind, placebo-controlled trials of 16 mg implants every 60 days in adults with erythropoietic protoporphyria (Langendonk 2015). In the US trial (94 patients, 3 implants, 180 days) median pain-free direct sunlight exposure was 69.4 hours with afamelanotide versus 40.8 hours with placebo (p = 0.04). In the EU trial (74 patients, 5 implants, 270 days) it was 6.0 versus 0.8 hours (p = 0.005) and phototoxic reactions fell from 146 to 77. Quality of life improved in both trials; adverse events were mostly mild. Long-term observational registries support continued use under dermatologic surveillance.

Human evidence

Langendonk 2015 (NEJM): US study, 94 patients randomized 1:1 to afamelanotide or placebo implants every 60 days for 180 days; median pain-free sun exposure 69.4 versus 40.8 hours. EU study, 74 patients for 270 days; median 6.0 versus 0.8 hours of pain-free exposure, 77 versus 146 phototoxic reactions, improved quality of life. Serious adverse events were not attributed to the drug. Earlier phase 2 work and European post-marketing data (EU approval 2014) informed the FDA approval in 2019.

Animal evidence

Afamelanotide induces pigmentation in mice and guinea pigs and reduces UV induced DNA damage and inflammation in animal and human skin models. Melanocortin 1 receptor selectivity was established in receptor binding and cell assays.

Key studies

Conditions studied

Is Melanotan I (afamelanotide) legal in the United States?

FDA and compounding status

FDA approved as Scenesse (afamelanotide) implant on October 8, 2019, for adults with a history of phototoxic reactions from erythropoietic protoporphyria; the European Medicines Agency approved it in 2014. It is dispensed only through certified specialist centers because insertion requires training. Afamelanotide is not on any 503A or 503B bulks list; as the active ingredient of an approved drug it could in principle be compounded in another dosage form, but injectable Melanotan I sold online for tanning is not a compounded prescription product and is marketed unlawfully.

WADA status

Not WADA prohibited. Not named on the current prohibited list. Athletes should still confirm against the list in force for their season.

Regulatory timeline

1. Oct 8, 2019FDA

   FDA approves Scenesse (afamelanotide) for erythropoietic protoporphyria

   FDA approved afamelanotide implant (Scenesse) to increase pain-free light exposure in adults with a history of phototoxic reactions from erythropoietic protoporphyria. Afamelanotide is the only approved melanotan-class peptide.

   Regulatory: FDA approvedSource: Drugs@FDA: Scenesse (afamelanotide) NDA 210797

Full tracker for Melanotan I (afamelanotide) or the category-wide tracker.

Melanotan I (afamelanotide) dose on the FDA label

Doses below are quoted from the FDA label for its approved uses, plus the doses used in the pivotal trials where noted. The prescriber sets the dose; PeptideAgent does not recommend doses or protocols.

FDA label (Scenesse, DailyMed): one implant containing 16 mg of afamelanotide inserted subcutaneously above the anterior supra-iliac crest every 2 months by a healthcare professional who has completed the manufacturer's implantation training, with sun and light protection maintained during treatment. The label covers only adults with a history of phototoxic reactions from erythropoietic protoporphyria; no dose is established for tanning or any cosmetic use.

Routes reported

What are the side effects and interactions of Melanotan I (afamelanotide)?

Side effects

Interactions

Contraindications

How do people access Melanotan I (afamelanotide) legally?

Typical cost: Specialty orphan drug priced in the tens of thousands of USD per implant before insurance, with several implants per year; insurance and manufacturer support programs determine out of pocket cost for approved patients. It is not sold for cosmetic use. Gray market Melanotan I vials are not lawful for human use and are not verified for purity.

• Rules by state
• Verified provider directory

Compare Melanotan I (afamelanotide)

• Melanotan I (afamelanotide) vs Melanotan II

Frequently asked questions

Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.

From the blog

• Melanotan 1 before and after: what the afamelanotide trials measured

  Melanotan 1 is afamelanotide, approved only as an implant for a rare light sensitivity disease. What the tanning and approval trials measured, what happens to moles, and why tanning use is unapproved.

• Melanotan 2 before and after: what trials and case reports show

  Melanotan 2 before and after photos show a tan. Early trials measured it in a few men; case reports since document new moles, melanoma, priapism and FDA safety concerns.

Sources

Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.