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Afamelanotide (MT-1)

Selective melanocortin-1 receptor (MC1R) agonist

Also known as Melanotan I, Scenesse, NDP-MSH

The melanocortin agonist that completed development. Approved for a rare light-sensitivity disorder, and the direct counterexample to melanotan II.

Guide updated Sep 2, 2026Literature checked Sep 2, 20261 curated study37 literature recordsBaseline editorial

Overview

In shortAn implant that prevents sunlight-triggered pain in adults with a rare inherited condition. It is here deliberately, because it gets confused with melanotan II, which shares an origin and nothing else. This one is selective, was properly trialled, is approved, and is given under supervision. The other is not selective, not approved, and carries a published record of harm.

Afamelanotide is a selective MC1R agonist, delivered as a subcutaneous implant, approved to prevent phototoxicity in adults with erythropoietic protoporphyria, a rare inherited condition in which sunlight causes severe pain.

Its presence here is deliberate. It is often confused with melanotan II, which shares an origin and shares nothing else: afamelanotide is selective, was properly trialled, is approved, and is administered under supervision, while melanotan II is non-selective, unapproved, and carries a case-report literature of harm.

Mechanism

In shortIt tells pigment cells to make more of the dark pigment that absorbs and disperses light energy in the skin, which reduces the painful reaction in people with this condition. Being selective is the whole design: by leaving the other related receptors alone it produces the tanning without the appetite, nausea and sexual effects that dominate the non-selective compounds.

MC1R agonism on melanocytes increases eumelanin production, which absorbs and dissipates light energy in the skin. In erythropoietic protoporphyria that reduces the phototoxic reaction driven by accumulated protoporphyrin IX.

Selectivity is the whole design. By avoiding meaningful MC3R and MC4R activity, it produces pigmentation without the appetite, nausea, and sexual-response effects that dominate the non-selective compounds.

Evidence

In shortEstablished for the condition it treats. Trials reported more pain-free time in sunlight and better quality of life. They are small because the condition is rare, and the main measure relies on patient diaries, which is a real limitation. Nothing supports using it for cosmetic tanning, which is not an approved use anywhere.

Established within its indication. Randomised trials in erythropoietic protoporphyria reported increases in pain-free sunlight exposure time and improvements in quality of life.

Trials are small because the population is rare, and the primary endpoints rely on patient diaries, which is a real limitation in an unmasked-adjacent context. No evidence supports use for cosmetic tanning, which is not an approved indication anywhere.

Safety

In shortReported effects include nausea, headache, tiredness, implant site reactions and general skin darkening. Because it causes pigmentation, skin checks are part of the label, at the start and periodically after. That is the same theoretical concern melanotan II raises, but here it is handled inside a supervised programme with defined follow-up rather than left to the user.

Reported effects include nausea, headache, fatigue, implant site reactions, and generalised darkening of skin.

Because it induces pigmentation, skin monitoring is part of the labelling: baseline and periodic examination for melanocytic lesions. This is the same theoretical concern as melanotan II, but here it is managed inside a supervised programme with defined follow-up rather than left to the user.

Regulatory status

In shortApproved in the EU, the US and elsewhere for that rare condition, given as an implant by a clinician under a controlled programme. Not approved for tanning anywhere.

Approved in the European Union, the United States and elsewhere for erythropoietic protoporphyria. Administered as a clinician-implanted device under a controlled programme. Not approved for tanning in any jurisdiction.

The literature

1 study indexed. Findings and limitations get equal weight, on purpose.

Always check the primary source

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The Afamelanotide literature needs an account

Everything above is free to read. What an account opens is the evidence underneath it: 1 study with their limitations, and the regimen each trial actually reported.

  • Every study, with what it found and what it cannot show
  • The limitations, given the same weight as the findings
  • The dose each named trial administered, where recorded
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The wider literature

17 indexed papers and 20 registered trials mentioning Afamelanotide, straight from PubMed and ClinicalTrials.gov. 20 of 20 administer it; the rest measure it. These have not been read by us. Unlike the studies above, they carry no findings and no limitations written by anyone here, because writing either would mean claiming a reading nobody has done. They are a starting point for yours.

Registered trials (20)

  1. Pharmacokinetics of Afamelanotide in Erythropoietic Protoporphyria Patients

    Clinuvel Europe Limited2024NCT06388642

    interventionalphase1phase2completedn=28

  2. Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Variegate Porphyria (VP)

    Clinuvel Pharmaceuticals Limited2023NCT05854784

    interventionalphase2completedn=6

  3. 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

    Clinuvel, Inc.2023NCT06109649

    interventionalphase3active not recruitingn=200

  4. A Study to Assess the Changes in Pigmentation and Safety of Afamelanotide in Patients With Vitiligo on the Face

    Clinuvel, Inc.2022NCT05210582

    interventionalphase2unknownn=6

  5. DNA Repair Capacity of Afamelanotide on Ultraviolet Radiation-induced DNA Damage in Healthy Volunteers

    Clinuvel (UK) Ltd.2022NCT05368857

    interventionalphase1completedn=10

  6. A Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Xeroderma Pigmentosum C and V

    Clinuvel Europe Limited2022NCT05370235

    interventionalphase2unknownn=6

  7. A Study to Evaluate the Safety and Efficacy of Afamelanotide in Patients With Xeroderma Pigmentosum (XP)

    Clinuvel Europe Limited2021NCT05159752

    interventionalphase2unknownn=6

  8. A Proof of Concept Study to Evaluate the Safety of Afamelanotide in Patients With Acute Arterial Ischaemic Stroke (AIS)

    Clinuvel Pharmaceuticals Limited2021NCT04962503

    interventionalphase2completedn=6

  9. Phase III Confirmatory Study in Erythropoietic Protoporphyria

    Clinuvel Pharmaceuticals Limited2012NCT01605136

    interventionalphase3completedn=93

  10. A Safety Extension Study in Patients With Erythropoietic Protoporphyria (EPP)

    Clinuvel Pharmaceuticals Limited2011NCT04578496

    interventionalphase3completedn=16

  11. Afamelanotide and Narrow-Band Ultraviolet B (NB-UVB) Light in the Treatment of Nonsegmental Vitiligo

    Clinuvel Pharmaceuticals Limited2011NCT01382589

    interventionalphase2completedn=15

  12. Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP)

    Clinuvel Pharmaceuticals Limited2010NCT01097044

    interventionalphase2completedn=77

  13. Afamelanotide in Patients Suffering With Acne Vulgaris

    Clinuvel Pharmaceuticals Limited2010NCT04943159

    interventionalphase2completedn=3

  14. Afamelanotide in Patients Suffering From Polymorphic Light Eruption (PLE)

    Clinuvel Pharmaceuticals Limited2010NCT04704713

    interventionalphase3completedn=31

  15. Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)

    Clinuvel Pharmaceuticals Limited2009NCT00979745

    interventionalphase3completedn=74

  16. Implant Pharmacokinetic and Pharmacodynamic Study

    Clinuvel Pharmaceuticals Limited2009NCT03634137

    interventionalphase1completedn=24

  17. Afamelanotide as Adjunctive Therapy in Patients Undergoing Photodynamic Therapy (PDT) Utilising Porfimer Sodium

    Clinuvel Pharmaceuticals Limited2008NCT04425746

    interventionalphase2completedn=16

  18. Phase II Solar Urticaria (SU) Pilot Study

    Clinuvel Pharmaceuticals Limited2008NCT00859534

    interventionalphase2completedn=5

  19. Phase II AK Study in Organ Transplant Patients

    Clinuvel Pharmaceuticals Limited2007NCT00829192

    interventionalphase2unknownn=200

  20. Multicentre Phase III Erythropoietic Protoporphyria Study

    Clinuvel Pharmaceuticals Limited2007NCT04053270

    interventionalphase3completedn=100

Papers (17)

  1. Intercepting the complement amplification loop through podocyte MC5R signaling ameliorates membranous nephropathy.

    Liu J, et al.Molecular therapy : the journal of the American Society of Gene Therapy2025PMID 40739753

    journal article

  2. Erythropoietic protoporphyrias: Pathogenesis, diagnosis and management.

    Minder AE, et al.Liver international : official journal of the International Association for the Study of the Liver2025PMID 39011756

    journal articlereviewresearch support, non-u.s. gov't

  3. Afamelanotide in protoporphyria and other skin diseases: a review.

    Polańska A, et al.Postepy dermatologii i alergologii2024PMID 38784937

    journal articlereview

  4. Targeting the central melanocortin system for the treatment of metabolic disorders.

    Sweeney P, et al.Nature reviews. Endocrinology2023PMID 37365323

    journal articlereviewresearch support, n.i.h., extramuralresearch support, non-u.s. gov't

  5. 2023PMID 40258105

    review

  6. Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art.

    Diotallevi F, et al.International journal of molecular sciences2023PMID 36902341

    journal articlereview

  7. Vitiligo: Pathogenesis and New and Emerging Treatments.

    Perez-Bootello J, et al.International journal of molecular sciences2023PMID 38139134

    journal articlereview

  8. Phototherapy for Vitiligo.

    Zubair R, et al.Dermatologic clinics2020PMID 31753192

    journal articlereview

  9. From pathogenesis of acne vulgaris to anti-acne agents.

    Cong TX, et al.Archives of dermatological research2019PMID 30859308

    journal articlereview

  10. [Porphyrias-what is verified?].

    Stölzel U, et al.Der Internist2018PMID 30328490

    journal articlereview

  11. An overview of the cutaneous porphyrias.

    Dawe RF1000Research2017PMID 29152226

    journal articlereview

  12. [Undesirable pigmentation].

    Bayerl CDer Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete2015PMID 26315100

    english abstractjournal articlereview

  13. An α-MSH analog in erythropoietic protoporphyria.

    Luger TA, et al.The Journal of investigative dermatology2015PMID 25785940

    editorial

  14. Afamelanotide.

    2012PMID 38598652

    review

  15. Use of melanotan I and II in the general population.

    Evans-Brown M, et al.BMJ (Clinical research ed.)2009PMID 19224885

    editorial

  16. X-Linked Protoporphyria.

    Adam MP, et al.1993PMID 23409301

    review

  17. Erythropoietic Protoporphyria, Autosomal Recessive.

    Adam MP, et al.1993PMID 23016163

    review

Discussion

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For Research & Educational Discussion Only. Not Medical Advice

This guide is educational reference material compiled from published literature. It is not medical advice, not a recommendation, and not a substitute for a clinician who knows your history. Nothing here should be used to make a decision about your own health without one.

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