Afamelanotide (Melanotan I)

AApproved (Rx) — erythropoietic protoporphyriaMelanocortin agonists →Melanotan IMelanotan-1Scenesse
In one paragraphAfamelanotide is a linear analogue of the pigment hormone α-MSH, developed in the 1980s as the first 'Melanotan'. It is an approved medicine — as a subcutaneous implant replaced every two months — for erythropoietic protoporphyria, a genetic disorder in which sunlight causes severe pain within minutes. In two randomised trials it roughly doubled the hours patients could spend in direct sun without pain. The same molecule is sold illegally as a tanning injection; for that use there is no approval and no controlled evidence of safety.
Schematic 3D structure of Afamelanotide (Melanotan I)
13 residues · linear α-MSH analogue · schematic
Overall gradeA Established
Human trials2 phase 3 RCTs (n=168) + long-term registry data
Outcomes graded4
Last reviewed10 September 2026
EvidenceWhat it isHow it worksUnknownsMolecule & PKRegulationQuestionsReferences

What the human research shows

One of the few grey-market peptides that graduated into a real medicine — for a disease most people have never heard of. The tanning use it started life as has never been approved anywhere.

MetabolicCardioMuscleHealingNeuroImmuneSexualSkinAgeing

Evidence profile0–5

  • Metabolic & weight—0.0
  • Cardiovascular—0.0
  • Muscle & growth—0.0
  • Healing & repairA3.3
  • Neuro & sleep—0.0
  • Immune & inflammation—0.0
  • Sexual & hormonal—0.0
  • Skin & appearanceB3.5
  • Ageing & longevity—0.0
Each score is confidence × effect size, taken from the best-evidenced benefit in that domain: the grade (A–D) sets the confidence, the measured effect sets the size. Hover a domain to see the outcomes behind it. Adverse effects are excluded and listed separately below.
OutcomeGradeEffect sizeHuman studiesWhere the evidence comes from
Pain-free sun exposure in erythropoietic protoporphyriaAEstablishedModerate2 phase 3 RCTs (EU n=74, US n=94)In both trials patients on afamelanotide implants spent significantly longer in direct sunlight without pain; the EU trial also counted fewer phototoxic reactions. Quality of life improved in both.1
Skin pigmentation (tanning)BProbableLargeEarly trials + the phase 3 programmeIt darkens skin reliably — that is its mechanism, and hyperpigmentation is the expected effect in every trial. What has never been studied is the safety of using it for cosmetic tanning in healthy people, and no regulator has approved that use.1
Vitiligo repigmentationCWeakSmallSmall RCTs with phototherapySmall trials combining the implant with narrowband UVB reported faster repigmentation than phototherapy alone. Not an approved indication.3
Adverse effectsadverseAEstablishedSmallPhase 3 + registryNausea, headache and implant-site reactions; darkening of skin and moles, which requires skin monitoring on treatment. Serious events in the trials were not judged drug-related.1
AMultiple good human trials, consistentBSome human trials, mostly consistentCFew or weak human studiesDAnimal or anecdotal onlyeffect size · red = adverse

Literature searched to 10 September 2026. Human studies only; animal and cell work informs the mechanism section and nothing else.

Registered trials

ClinicalTrials.gov lists 22 interventional studies naming Afamelanotide (Melanotan I) as an intervention — 17 completed, and 12 with results posted to the registry.

A registration is not a result. Anyone can register a study, and many never report — so this list shows what has been attempted, not what has been shown. The graded evidence above is the answer to whether something works.

StudyPhaseStatusParticipantsSponsorResults
Multicentre Phase III Erythropoietic Protoporphyria StudyNCT04053270 · started May 2007Phase 3Completed100Clinuvel Pharmaceuticals LimitedPosted
Phase III Confirmatory Study in Erythropoietic ProtoporphyriaNCT01605136 · started May 2012Phase 3Completed93Clinuvel Pharmaceuticals LimitedPosted
Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP)NCT00979745 · started Sept 2009Phase 3Completed74Clinuvel Pharmaceuticals LimitedPosted
Afamelanotide in Patients Suffering From Polymorphic Light Eruption (PLE)NCT04704713 · started May 2010Phase 3Completed31Clinuvel Pharmaceuticals LimitedPosted
A Safety Extension Study in Patients With Erythropoietic Protoporphyria (EPP)NCT04578496 · started Jul 2011Phase 3Completed16Clinuvel Pharmaceuticals LimitedPosted
Phase II Confirmatory Study in Erythropoietic Protoporphyria (EPP)NCT01097044 · started Apr 2010Phase 2Completed77Clinuvel Pharmaceuticals LimitedPosted
Afamelanotide and Narrow-Band Ultraviolet B (NB-UVB) Phototherapy in the Treatment of Nonsegmental Vitiligo (NSV)NCT04525157 · started Jun 2014Phase 2Completed21Clinuvel Pharmaceuticals LimitedPosted
Afamelanotide as Adjunctive Therapy in Patients Undergoing Photodynamic Therapy (PDT) Utilising Porfimer SodiumNCT04425746 · started Aug 2008Phase 2Completed16Clinuvel Pharmaceuticals LimitedPosted

14 further studies are registered. Participant counts marked * are the sponsor's estimate, not a final enrolment. Source: ClinicalTrials.gov, read directly from the registry and refreshed weekly.

What it is

Afamelanotide is α-MSH with two substitutions that make it far more potent and longer-lasting, designed at the University of Arizona in the 1980s — the same programme that produced Melanotan II. Clinuvel developed it as Scenesse, a 16 mg implant the size of a grain of rice, inserted under the skin every 60 days.

It was approved in the EU in 2014 under exceptional circumstances, in the United States in 2019, and in Australia — the first medicine of its kind for erythropoietic protoporphyria.

How it is thought to work

It activates the MC1 receptor on melanocytes, increasing eumelanin — the photoprotective brown-black pigment — without UV exposure. In protoporphyria, where light triggers a toxic reaction in the skin, more pigment means more light absorbed before it reaches the sensitive layers.

What is still unknown

  • Long-term effects on melanocytic naevi and melanoma risk, which is why treated patients are monitored; registry data so far have not shown an excess.
  • Safety in healthy people using it cosmetically — never studied.

The molecule and how long it lasts

Identity
Formula
C78H111N21O19
Molecular weight
1646.8 g/mol
CAS number
75921-69-6
PubChem
CID 16197727

PubChem record, read 23 September 2026.

Pharmacokinetics
Route
Subcutaneous implant, every 2 months
Half-life
About 15 hours (apparent, from implant)
Licensed regimen (Scenesse)
Single 16 mg implant inserted subcutaneously every 2 months

From the approved product's prescribing information: Scenesse prescribing information (DailyMed) The regimen is the label's own wording, reproduced as a regulatory fact.

Regulatory status

European Union
Approved, prescription-only

Centrally authorised (Scenesse) in 2014 under exceptional circumstances for erythropoietic protoporphyria. Tanning use is not authorised; injectable 'Melanotan' products are illegal.

United States
Approved, prescription-only

FDA-approved October 2019 for erythropoietic protoporphyria, implant only.

United Kingdom
Licensed, prescription-only

Licensed for erythropoietic protoporphyria. The MHRA has repeatedly warned against injectable tanning products.

Australia
Registered, prescription-only

On the ARTG for erythropoietic protoporphyria; the developer is Australian.

Canada
Not authorised

LYO found no Health Canada authorisation at review.

Sport (WADA)
Not prohibited

Not on the Prohibited List.

Questions people actually ask

Is Melanotan I the same as Melanotan II?
No. Melanotan I is linear and selective for the pigment receptor; Melanotan II is cyclic and hits several melanocortin receptors, which is why it also causes erections and nausea. Melanotan I became an approved medicine; Melanotan II did not.
Can you get afamelanotide for tanning?
Not lawfully. It is approved only for erythropoietic protoporphyria, as an implant placed by a clinician. The injectable 'Melanotan I' sold online is an unlicensed product of unknown content.
Does it cause skin cancer?
Unknown; it is the main open safety question. It darkens moles, so treated patients have regular skin checks. Registry data over years of licensed use have not shown an excess so far.

One page per claimed effect

References

  1. 1
  2. 2
    Scenesse (afamelanotide) — European public assessment report.EMA, 2014 onwardLicensed indication and conditions.
  3. 3

Change log

  • 2026-09-10Initial publication. Grade A for erythropoietic protoporphyria on two phase 3 RCTs.