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Afamelanotide

What it is. What the evidence says.

A lab-made copy of a natural skin-darkening hormone (alpha-MSH). It tells pigment cells to make more melanin, the brown pigment in skin.

Moderate EvidenceApproved Medicine

Predominant research setting. Clinical confidence is claim-specific.

Updated Scientific review pending
Start with the basics Regulatory status ↓
Sequence diagram and chemical structure information for Afamelanotide.
Afamelanotide Chemical Structure & Sequence · Inside Peptides Scientific Library
Compound
Afamelanotide (as acetate)
Human effectiveness
Two randomized Phase 3 trials showed more pain-free time in light for adults with EPP; effect sizes were modest and endpoints self-reported
Regulatory status
FDA-Approved Medicine
START HERE · PLAIN LANGUAGE

Afamelanotide: the basics

What is it?

A lab-made copy of a natural skin-darkening hormone (alpha-MSH). It tells pigment cells to make more melanin, the brown pigment in skin.

Research paper 1 ↗Research paper 2 ↗

What do people claim it helps with?

Less pain from light for people with erythropoietic protoporphyria (EPP), a rare inherited disease. Some people also hope to use it for tanning or vitiligo, which are not approved uses.

What has research actually shown?

Two controlled trials found adults with EPP could spend more time in sunlight without pain and had better quality of life, though the gains were modest.

Research paper 1 ↗Research paper 2 ↗

Has this been demonstrated in people?

Demonstrated in people with EPP in two randomized trials and a long-term observational study; vitiligo results come from a small trial.

Research paper 1 ↗Research paper 2 ↗

What side effects, risks and unknowns should I understand?

Implant-site reactions, nausea, sore throat, cough, tiredness, dizziness and skin darkening are common. Moles and freckles can darken, so a full skin check twice a year is advised. Serious allergic reactions have been reported.

Prescribing information ↗

Is it an approved medicine?

Yes. Scenesse is FDA-approved to increase pain-free light exposure in adults with a history of light reactions from EPP. It is not approved for tanning, vitiligo or children.

FDA safety information 1 ↗Prescribing information 2 ↗

Approval here means U.S. FDA approval and applies to a particular product, formulation and use. This is a starting overview, not a complete side-effect list. Sources checked 10 October 2026; independent scientific review pending.

How is it used or studied?

A tiny dissolving rod implanted under the skin by a trained health professional; it is not a self-injected product.

Different routes and formulations can have different effects. A study of one product does not validate every product with the same peptide name.

A common misunderstanding

Afamelanotide is not melanotan II. Melanotan II is a different, unapproved peptide sold online for tanning, with its own safety reports.

What should I ask a clinician?
  • What diagnosis or goal are we trying to address, and what established options are available?
  • Was the expected benefit shown in people like me, using this exact product?
  • How could my medicines, health conditions or pregnancy plans affect the risks?
  • What monitoring is needed, and what would tell us the treatment is helping or should be stopped?
What do the research words mean?
Peptide
A short chain of amino acids, the building blocks of proteins.
Preclinical
Research in cells, tissues or animals before dependable treatment evidence in people.
Controlled trial
A study comparing a treatment with another treatment or a placebo to help separate its effects from other explanations.
Biomarker
A measurement, such as a hormone level. A change does not necessarily mean someone feels better or lives longer.
THE AVAILABLE RESEARCH

Afamelanotide Evidence & Clinical Profile

Human Clinical Evidence

Established Clinical Trials

Afamelanotide has been investigated in clinical contexts. Patient outcomes must be evaluated against study size, design, and control cohorts.

Preclinical & Pharmacological Data

Laboratory & In Vivo Assays

Cellular and animal disease models examine receptor binding affinities and signaling cascades, which require human confirmation.

Understand our evidence labels →

IDENTITY & STRUCTURE

What is Afamelanotide?

Afamelanotide (Scenesse implant) is Afamelanotide is a 13-amino-acid synthetic analogue of alpha-melanocyte-stimulating hormone (alpha-MSH) that mainly activates the MC1 receptor and darkens skin by increasing eumelanin, without sun exposure. As the Scenesse implant (Clinuvel), it is FDA-approved to increase pain-free light exposure in adults with erythropoietic protoporphyria (EPP), a rare inherited condition that causes severe pain after light exposure. Aliases include: Scenesse, CUV1647, [Nle4, D-Phe7]-alpha-MSH, NDP-MSH.

Chemical sequence and molecular parameters of Afamelanotide
Primary sequence schematic · Inside Peptides Molecular Database
Chemical reference
Sequence (one-letter)
Ac-SYS-Nle-EH-dF-RWGKPV-NH2
Molecular formula
C78H111N21O19
Molecular weight
1646.8 g/mol
CAS Number
75921-69-6
UNII Code
QW68W3J66U
PubChem CID
16197727

Identifiers are for the free base. The approved implant contains afamelanotide acetate (UNII 1XCC161YKC).

Identifiers checked against PubChem and FDA's Global Substance Registration System on 13 October 2026. FDA substance record ↗ · PubChem record ↗ See all names and codes in the peptide name index.

HUMAN RESEARCH

Clinical Trials & Human Cohorts

Human research can examine tolerability, symptoms or patient outcomes. The design and comparator determine what each result can establish.

Two multicenter, randomized, double-blind, placebo-controlled trials (EU 180 days, U.S. 270 days)2015

Afamelanotide for Erythropoietic Protoporphyria [1]

n = 16874 patients in the EU trial and 94 in the U.S. trial with EPP

What was reported

Median pain-free direct-sunlight time was longer with afamelanotide (U.S.: 69.4 vs 40.8 hours over 6 months; EU: 6.0 vs 0.8 hours over 9 months). Phototoxic reactions were fewer in the EU trial (77 vs 146) and quality of life improved.

What limits the conclusion

Endpoints relied on patient diaries of sun exposure and pain. Absolute gains were modest and the studies were funded by the manufacturer. Adverse events were mostly mild.

Read primary source ↗ (external website)
Observational study at two porphyria centres (Rome and Zurich); up to 8 years2015

Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria [2]

n = 115Ambulatory EPP patients treated with 1023 implants in total

What was reported

EPP-specific quality-of-life scores rose from 31% of maximum before treatment to about 74% and stayed there; only minor treatment-related adverse events, mostly nausea, were recorded.

What limits the conclusion

No control group and run by specialist centres, so improvement cannot be fully separated from expectation or patient selection. 23% stopped, mostly for reasons such as pregnancy or cost.

Read primary source ↗ (external website)
Randomized multicenter trial: afamelanotide plus narrowband UV-B vs narrowband UV-B alone2015

Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial [3]

n = 55Adults with nonsegmental vitiligo and Fitzpatrick skin types III to VI

What was reported

Repigmentation at day 168 was 48.6% with the combination vs 33.3% with phototherapy alone, with faster response on the face and upper limbs; benefit was clearest in skin types IV to VI.

What limits the conclusion

Small trial; no benefit seen in skin type III. Vitiligo is not an approved use, and a Phase 3 trial was still active (not recruiting) at last registry update.

Read primary source ↗ (external website)
MECHANISMS OF ACTION

How the compound may work

Mechanisms describe how Afamelanotide may affect biological processes. Laboratory findings and patient outcomes answer different questions.

01
Established pharmacology (U.S. label)

MC1 receptor agonist

Afamelanotide is a structural analogue of alpha-MSH that binds mainly to the MC1 receptor on melanocytes and increases eumelanin production in the skin, independent of sunlight or UV exposure. [4]

02
U.S. label pharmacokinetics

Slow-release implant

The peptide is mixed into a small bioresorbable polymer rod. Plasma levels were highly variable between people; the apparent half-life from the implant is about 15 hours. [4]

RESEARCH AREAS

Areas Being Studied

These research topics reflect active areas of scientific exploration, distinct from unverified commercial marketing claims.

Phase 3 trials and long-term cohort

Erythropoietic protoporphyria

The approved use: reducing light-triggered pain episodes and increasing tolerated light exposure. [1]

Phase 2 randomized trial; Phase 3 ongoing

Vitiligo

Combined with narrowband UV-B phototherapy to speed repigmentation, mainly in darker skin types. [3]

AT A GLANCE

Compare the study designs.

Overview of Key Afamelanotide Studies: clinical and preclinical records
Study Design / sample Outcome type Key limitation
EPP Phase 3 trials (EU and U.S.) · 2015 [1] Two multicenter, randomized, double-blind, placebo-controlled trials (EU 180 days, U.S. 270 days)
n = 168		 Clinical endpoint evaluation Endpoints relied on patient diaries of sun exposure and pain. Absolute gains were modest and the studies were funded by the manufacturer. Adverse events were mostly mild.
Long-term use in 115 patients · 2015 [2] Observational study at two porphyria centres (Rome and Zurich); up to 8 years
n = 115		 Clinical endpoint evaluation No control group and run by specialist centres, so improvement cannot be fully separated from expectation or patient selection. 23% stopped, mostly for reasons such as pregnancy or cost.
Vitiligo with NB-UVB (Phase 2) · 2015 [3] Randomized multicenter trial: afamelanotide plus narrowband UV-B vs narrowband UV-B alone
n = 55		 Clinical endpoint evaluation Small trial; no benefit seen in skin type III. Vitiligo is not an approved use, and a Phase 3 trial was still active (not recruiting) at last registry update.
FDA & SAFETY

Regulatory Status & Clinical Safety

Regulatory Classification

United States, checked 11 October 2026: Scenesse (NDA 210797, Clinuvel) is approved to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria. It is a bioresorbable implant inserted under the skin by a trained health care professional. Safety and effectiveness in children have not been established. Patients still need sun and light protection. Vitiligo and other uses are investigational. Not named on the WADA Prohibited List to our knowledge.

Safety Realities & Impurities

Safety depends on the molecule, formulation, route and evidence. A laboratory purity measurement alone cannot establish safety for human use.

REGISTRY CHECK

Clinical Trials Registry Records

Official registry records from ClinicalTrials.gov. Study registration does not imply government endorsement or guaranteed efficacy.

Phase 3Completed

Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP) [6]

Planned enrollment
74 (actual enrollment)
Posted results
Available
Sponsor
Clinuvel Pharmaceuticals Limited
Last updated
2021-10-12
NCT00979745 · Open registry ↗ (external website)
Phase 3Active, not recruiting

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 [8]

Planned enrollment
200 (estimated enrollment)
Posted results
Pending in registry
Sponsor
Clinuvel, Inc.
Last updated
2025-07-08
NCT06109649 · Open registry ↗ (external website)
COMPETITIVE SPORT

WADA & Anti-Doping Regulations

Not Prohibited

WADA Anti-Doping Status

Afamelanotide is not prohibited under current World Anti-Doping Agency (WADA) regulations. However, athletes must ensure unregulated preparations or unverified vendor products do not violate Section S0 (Non-approved substances). Last verified: October 2026.

SELECTED MILESTONES

Research Timeline

  1. 2015

    Phase 3 results published

    NEJM reports the EU and U.S. randomized EPP trials. [1]

  2. 2015

    Long-term cohort

    Two European porphyria centres report up to 8 years of routine use in 115 patients. [2]

  3. 2019

    FDA approval

    FDA approves Scenesse (NDA 210797) for adults with EPP. [5]

  4. 2026

    Current status

    Approved for adult EPP only; vitiligo remains under investigation. [4]

OPEN QUESTIONS

What Researchers Still Don't Know

Long-term safety profiles

Multi-year observational data in broader heterogeneous cohorts remains uncharacterized.

Optimal dose-response thresholds

Comparative trials optimizing minimal effective exposure versus adverse event rates.

Formulation bioavailability

Differences between oral, subcutaneous, and modified peptide delivery vehicles.

TRACEABLE SOURCES

References

Primary sources verified against PubMed / NLM and regulatory databases.

  1. Phase 3 RCTs

    Afamelanotide for Erythropoietic Protoporphyria ↗ (external website)

    Langendonk JG et al. · N Engl J Med · 2015 DOI: 10.1056/NEJMoa1411481 ↗ (external website)
  2. Observational study

    Long-term observational study of afamelanotide in 115 patients with erythropoietic protoporphyria ↗ (external website)

    Biolcati G et al. · Br J Dermatol · 2015 DOI: 10.1111/bjd.13598 ↗ (external website)
  3. Randomized trial

    Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial ↗ (external website)

    Lim HW et al. · JAMA Dermatol · 2015 DOI: 10.1001/jamadermatol.2014.1875 ↗ (external website)
  4. Official prescribing information

    Scenesse (afamelanotide) implant, current U.S. label ↗ (external website)

    DailyMed / National Library of Medicine · 2026

    Clinuvel SPL published May 2026; checked 11 October 2026.

  5. FDA approval record

    Drugs@FDA: Scenesse, NDA 210797 ↗ (external website)

    U.S. FDA · 2026

    Original approval 8 October 2019.

  6. Official registry

    Phase III Confirmatory Study in Erythropoietic Protoporphyria (EPP) ↗ (external website)

    ClinicalTrials.gov · 2021

    API record checked 11 October 2026.

  7. Official registry

    Phase III Confirmatory Study in Erythropoietic Protoporphyria ↗ (external website)

    ClinicalTrials.gov · 2019

    API record checked 11 October 2026.

  8. Official registry

    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 ↗ (external website)

    ClinicalTrials.gov · 2025

    API record checked 11 October 2026.