← All compounds · evidence tier first, by design
| Use | E1 | E2 | E3 | E4 | E5 | E6 | E7 | E8 |
|---|---|---|---|---|---|---|---|---|
| E1 Phototoxicity in erythropoietic protoporphyria (adults) | E1 | |||||||
| E3 Nonsegmental vitiligo (with narrowband UV-B phototherapy) | E3 | |||||||
| E3 Cosmetic tanning in healthy people (gray-market 'Melanotan-1' claim) | E3 |
Afamelanotide
Linear tridecapeptide analogue of alpha-MSH: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, per the US prescribing information. Contains norleucine and a D-amino acid, so no plain one-letter sequence is given.
Non-standard residues or modifications: no plain one-letter sequence
Also: Melanotan-1, MT-1, [Nle4, D-Phe7]-alpha-MSH · Codes: CUV1647 · Brands: Scenesse
A synthetic analogue of alpha-melanocyte-stimulating hormone that binds mainly to the melanocortin-1 receptor and increases eumelanin in the skin. It is approved as a controlled-release subcutaneous implant (Scenesse) for adults with erythropoietic protoporphyria (EPP), a rare inherited condition causing painful reactions to light, in the US, EU, UK, Canada and Australia. The same molecule (Melanotan-1) is also sold as unapproved powder for cosmetic tanning; that material is not the approved product.
- US A approved
- EU A approved
- UK A approved
- CA A approved
- AU A approved
- JP ? not verified
- CN ? not verified
01Regulatory status, by jurisdiction
| Jurisdiction | Status | Detail and primary source |
|---|---|---|
| US | Approved | NDA 210797 (Scenesse implant), approved 8 October 2019 (priority review, orphan); applicant Clinuvel Inc. Latest label supplement 12 August 2024.“SCENESSE is a melanocortin 1 receptor (MC1-R) agonist indicated to increase pain free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP).”SCENESSE prescribing information (FDA, revised 08/2024) · retrieved 2026-10-10 |
| EU | Approved | Centrally authorised 22 December 2014 under exceptional circumstances; indication: prevention of phototoxicity in adult patients with EPP. Under additional monitoring.“The European Commission granted a marketing authorisation valid throughout the European Union for Scenesse on 22 December 2014.”Scenesse EPAR (EMA) · retrieved 2026-10-10 |
| UK | Approved | Great Britain marketing authorisation PLGB 30619/0002; SmPC retrieved from the MHRA products database (document dated 12 June 2026).“SCENESSE is indicated for prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP).”SCENESSE Summary of Product Characteristics (MHRA products database) · retrieved 2026-10-10 |
| CA | Approved | Drug Product Database: SCENESSE, DIN 02569825, Clinuvel Inc.; status Approved on 9 July 2026, with no market date recorded on the retrieval date (approved, not yet recorded as marketed).“Current status: Approved Current status date: 2026-07-09”Health Canada Drug Product Database: SCENESSE · retrieved 2026-10-10 |
| AU | Approved | ARTG 327947, sponsor Clinuvel Pharmaceuticals Ltd, ARTG start date 18 November 2020, status Active; medicine under additional monitoring. Afamelanotide is also a Schedule 4 (prescription-only) substance in the Poisons Standard.“SCENESSE is indicated for prevention of phototoxicity in adult patients with erythropoietic protoporphyria (EPP)”TGA ARTG Public Summary 327947: SCENESSE afamelanotide (as acetate) implant vial · retrieved 2026-10-10 |
| JP CN | Not yet verified from a primary source. No status is shown rather than an unsourced one. | |
Sport (WADA): Not prohibited. Not named on the Prohibited List. As an approved medicine it also falls outside class S0, which covers only substances without current regulatory approval: “Any pharmacological substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use” WADA source
02What the human evidence shows
Phototoxicity in erythropoietic protoporphyria (adults)
n/c: not counted here; see the cited review.
Two multicentre, double-blind, placebo-controlled RCTs (74 patients in the EU, 94 in the US) found longer pain-free direct sunlight exposure with afamelanotide (US median 69.4 versus 40.8 hours over 6 months; EU median 6.0 versus 0.8 hours over 9 months) and improved quality of life. An observational study of 115 patients treated for up to 8 years at two centres reported sustained use and only minor adverse events. The EU authorisation is under exceptional circumstances because comprehensive data could not be obtained.
- [1] Two RCTs: longer pain-free sunlight exposure and fewer phototoxic reactions (EU trial) than placebo in EPP
- [2] Sustained use and improved EPP quality-of-life scores over up to 8 years; mainly minor adverse events such as nausea
Registered-study counts: ClinicalTrials.gov intervention search “afamelanotide”, fetched 2026-10-10. Registered studies include trials of other uses; the gap between registered and reported is itself a finding.
Nonsegmental vitiligo (with narrowband UV-B phototherapy)
n/c: not counted here; see the cited review.
One small randomised multicentre trial (55 patients, skin phototypes III-VI) found faster and greater repigmentation with afamelanotide plus narrowband UV-B than with UV-B alone. A larger phase 3 trial is registered and active but had not reported on the retrieval date. Vitiligo is not an approved indication in any jurisdiction checked.
- [3] Greater and earlier repigmentation with combination therapy than narrowband UV-B alone in a 55-patient RCT
Registered-study counts: ClinicalTrials.gov intervention search “afamelanotide”, fetched 2026-10-10. Registered studies include trials of other uses; the gap between registered and reported is itself a finding.
Cosmetic tanning in healthy people (gray-market 'Melanotan-1' claim)
Three small phase 1 studies in healthy volunteers (two of them randomising 8 subjects each, one open-label with 12) reported skin darkening and enhanced tanning with sunlight or UV-B. These were safety studies of short duration. There is no evidence that induced tanning reduces skin cancer or sunburn in real-world use, and no data on gray-market material.
- [4] Enhanced tanning with sunlight or UV-B in small phase 1 studies of healthy volunteers; nausea and transient facial flushing reported
Registered-study counts: ClinicalTrials.gov intervention search “afamelanotide”, fetched 2026-10-10. Registered studies include trials of other uses; the gap between registered and reported is itself a finding.
Key registered trials
| NCT | Title (as registered) | Phase | Status |
|---|---|---|---|
| NCT01605136 | Phase III Confirmatory Study in Erythropoietic Protoporphyria | 3 | Completed |
| NCT00979745 | Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP) | 3 | Completed |
| NCT01097044 | Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP) | 2 | Completed |
| NCT06109649 | A Study to Compare the Efficacy and Safety of SCENESSE and Narrow-Band Ultraviolet (NB-UVB) Light Versus NB-UVB Light Alone in Patients With Vitiligo | 3 | Active, not recruiting |
03Safety signals
There are no adequate human safety data. The absence of reported harm is not evidence of safety.
- Serious hypersensitivity reactions, including anaphylaxis [5]
US prescribing information Warnings and Precautions 5.1. - Darkening of pre-existing naevi and ephelides [5]
US prescribing information Warnings and Precautions 5.2 (skin monitoring); periodic full-body skin examination is recommended in the label. - Nausea [2]
Most frequently recorded adverse event attributed to afamelanotide in long-term observational use.
04What is unknown
- Efficacy and safety in children and adolescents with EPP are not established
- Long-term melanocytic effects (naevus changes, melanoma risk) beyond observational follow-up of about a hundred patients are not characterised
- No adequately powered RCT in vitiligo has reported
- No data on identity, purity or sterility of gray-market 'Melanotan-1' powders, or on their safety outside the approved implant formulation
05Product quality
No independent purity results have been published for this compound yet. The purity programme will publish full methods and vendor-named results, passes and failures, once its protocol has had legal review.
06Citations
- Afamelanotide for Erythropoietic Protoporphyria (2015). doi:10.1056/nejmoa1411481
- Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria (2015). doi:10.1111/bjd.13598
- Afamelanotide and Narrowband UV-B Phototherapy for the Treatment of Vitiligo (2015). doi:10.1001/jamadermatol.2014.1875
- Effects of a Superpotent Melanotropic Peptide in Combination With Solar UV Radiation on Tanning of the Skin in Human Volunteers (2004). doi:10.1001/archderm.140.7.827
- SCENESSE (afamelanotide) implant, for subcutaneous use. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210797s007lbl.pdf
Every DOI is resolved against Crossref and every NCT number against ClinicalTrials.gov, title for title, before publication. Regulatory sources are cited inline above with a verbatim quote and retrieval date.
07Mechanism
Afamelanotide is an alpha-MSH analogue that binds predominantly to the melanocortin-1 receptor and increases eumelanin production in the skin independently of UV exposure.
Mechanism is placed last on purpose: a plausible mechanism is not evidence that a compound works in people.
Reviewed by OSMF research team (AI-assisted, source-verified) on 2026-10-10. Found an error? It goes in the corrections log: report it.