Afamelanotide

Also known as SCENESSE · [Nle4, D-Phe7]-alpha-MSH · NDP-MSH · CUV1647 · Melanotan I (historical research name)

FDA-approvedAHuman trial evidence What this means

Afamelanotide is a synthetic 13-amino-acid analogue of alpha-melanocyte-stimulating hormone that acts mainly at the melanocortin 1 receptor. It is approved by the FDA as SCENESSE, a 16 mg bioresorbable subcutaneous implant, to increase pain-free light exposure in adults with a history of phototoxic reactions from erythropoietic protoporphyria, and is authorised in the EU for prevention of phototoxicity in the same condition. This entry summarizes the FDA label and published trials for research reference only.

US status: FDA-approved
Evidence: Grade A
Half-life: Apparent half-life of approximately 15 hours when administered subcutaneously in the controlled-release implant; median Tmax 36 hours; in most subjects the last measurable concentration was at 96 hours after a single implant ¹
Class: Melanocortin 1 receptor (MC1-R) agonist; synthetic alpha-MSH analogue peptide (13 amino acids)

Studied in: Skin research · Class: Melanocortin-receptor peptides

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Unbranded reference vial illustrating Afamelanotide; not an actual product

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Key takeaways

Afamelanotide is an FDA-approved alpha-MSH analogue that binds predominantly to the melanocortin 1 receptor and increases eumelanin production in the skin independently of sunlight exposure ^1.
The FDA label covers one indication: increasing pain-free light exposure in adults with a history of phototoxic reactions from erythropoietic protoporphyria ^1.
In the US vehicle-controlled trial CUV039 (93 adults with EPP), median total hours in direct sunlight on pain-free days over 180 days were 64.1 with afamelanotide versus 40.5 with vehicle, per the label ^1.
Implant-site reactions (21% vs 10%), nausea (19% vs 14%) and skin hyperpigmentation (4% vs 0%) were among the adverse reactions more frequent than with vehicle through month 6 ^1.
The label recommends a twice-yearly full-body skin examination because pre-existing nevi and ephelides may darken, and lists serious hypersensitivity, including anaphylaxis, from postmarketing use ^1.

Development stage

Where Afamelanotide sits between laboratory work and regulatory approval.

Preclinical
Animal and cell work
Phase 1
First human safety studies
Phase 2
Early efficacy signal
Phase 3
Confirmatory trials
Approved (current)
Cleared by a regulator

Stage comes from the regulatory record and ClinicalTrials.gov studies naming the compound (for compounds approved nowhere, only completed trials or trials with posted results count) (checked 2026-10-24). A registered trial is not a result.

Mechanism of action

Afamelanotide is a synthetic tridecapeptide and structural analogue of alpha-melanocyte-stimulating hormone (alpha-MSH) that acts as a melanocortin receptor agonist, binding predominantly to MC1-R ¹.

Pigmentation

The FDA label states that afamelanotide increases production of eumelanin in the skin independently of exposure to sunlight or artificial UV light ¹. A pharmacology review describes MC1-R signalling as increasing melanin synthesis and also being linked to antioxidant activity, DNA repair processes and modulation of inflammation ⁶.

Formulation

The approved product is a solid bioresorbable rod in which the peptide is admixed with poly(DL-lactide-co-glycolide), providing controlled release after subcutaneous insertion ¹. A review reports that subcutaneous administration had full bioavailability in early volunteer work, whereas oral and transdermal administration did not produce measurable plasma concentrations or pigmentation ⁶.

Molecular structure

PubChem CID 16197727 ↗

2D depiction generated from the PubChem record. Depictions are schematic and do not show salt form, counter-ions or conformation.

Formula: C78H111N21O19
Molecular weight: 1646.8 g/mol
CAS: 75921-69-6
InChIKey: UAHFGYDRQSXQEB-LEBBXHLNSA-N

Research overview

Human research

Two multicentre randomized, double-blind, vehicle-controlled trials in adults with erythropoietic protoporphyria (74 in the EU, 94 in the US) reported longer pain-free direct sunlight exposure with afamelanotide than with vehicle, fewer phototoxic reactions in the EU trial, and improved quality-of-life scores ^4. In a randomized trial in 55 adults with nonsegmental vitiligo, adding afamelanotide to narrowband UV-B phototherapy was associated with faster and greater repigmentation than phototherapy alone, mainly in skin phototypes IV to VI ^5.

Animal research

The FDA label reports no adverse embryofetal or pre- and postnatal developmental effects and no effects on fertility in rats given subcutaneous afamelanotide, at exposures up to 12 times the maximum recommended human dose on a body-surface-area basis ^1.

In-vitro research

Afamelanotide was negative in the Ames test, the in vitro mouse lymphoma assay and the in vivo mouse bone marrow micronucleus assay; carcinogenicity studies have not been conducted ^1.

Key studies

Langendonk et al., N Engl J Med (CUV039, US) (2015)
Randomized, double-blind, placebo-controlled, multicenter, 94 participants, 180 days (NCT01605136)
Model: Humans (adults with erythropoietic protoporphyria)
After 6 months, median pain-free time in direct sunlight was 69.4 hours with afamelanotide versus 40.8 hours with placebo (P=0.04); adverse events were mostly mild and serious adverse events were not judged related to the study drug ^4.
Langendonk et al., N Engl J Med (CUV029, EU) (2015)
Randomized, double-blind, placebo-controlled, multicenter, 74 participants, 270 days (NCT00979745)
Model: Humans (adults with erythropoietic protoporphyria)
After 9 months, median pain-free time in direct sunlight was 6.0 hours with afamelanotide versus 0.8 hours with placebo (P=0.005), and phototoxic reactions numbered 77 versus 146 (P=0.04) ^4.
Lim et al., JAMA Dermatol (2015)
Randomized, multicenter, 55 participants, afamelanotide plus narrowband UV-B versus narrowband UV-B alone (NCT01430195)
Model: Humans (adults with nonsegmental vitiligo, Fitzpatrick skin phototypes III to VI)
Repigmentation at day 168 was 48.64% with combination therapy versus 33.26% with phototherapy alone; the difference was seen mainly in skin phototypes IV to VI, and notable adverse events included erythema in both groups and minor infections and nausea in the combination group ^5.
Lengweiler et al., Skin Pharmacol Physiol (2015)
Antibody assay development and testing of sera from 26 patients exposed to afamelanotide for up to 6 years
Model: Humans (patients with erythropoietic protoporphyria)
No anti-drug immunoreactivity was found in 23 of 26 patients; 3 had pre-existing immunoreactivity against afamelanotide and alpha-MSH whose titres did not change during administration ^7.

Dosing as stated on the FDA label

Quoted from the prescribing information for reference. Prescribing decisions belong to a licensed clinician; this is not a recommendation or instruction for use.

Full dosing reference, study durations and vial arithmetic →

SCENESSE (afamelanotide) implant 16 mg: insert a single implant subcutaneously every 2 months; the label directs that it be administered by a health care professional who is proficient in the subcutaneous implantation procedure and has completed the training program provided by CLINUVEL. ¹
Per the label, sun and light protection measures should be maintained during treatment with SCENESSE to prevent phototoxic reactions related to EPP, and patients should be monitored for 30 minutes after implant administration. ¹
Dosage form per the label: each implant contains 16 mg of afamelanotide (equivalent to 18 mg of afamelanotide acetate) as a solid, bioresorbable, sterile rod approximately 1.7 cm long and 1.45 mm in diameter. ¹
In study CUV039 (US, NCT01605136), 48 of 93 adults with EPP received a subcutaneous implant containing 16 mg afamelanotide every 2 months (three implants) and 45 received vehicle, with follow-up for 180 days ^1,4.
In study CUV029 (EU, NCT00979745), 38 of 74 adults with EPP received a subcutaneous implant containing 16 mg afamelanotide every 2 months (five implants) and 36 received vehicle, with follow-up for 270 days ^1,4.
In the vitiligo trial (NCT01430195), after 1 month of narrowband UV-B phototherapy, the combination group received 16 mg afamelanotide subcutaneously monthly for 4 months while phototherapy continued (28 participants), versus phototherapy alone (27 participants) ^5.

Afamelanotide draw calculator

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Published adverse-event data

Reported in the cited trials or product labels. Frequencies apply to the stated population and do not transfer to other settings.

Label warnings

Contraindication: history of severe hypersensitivity reaction to afamelanotide or to any of the excipients in SCENESSE. ¹
Hypersensitivity: serious hypersensitivity reactions, including anaphylaxis, have been reported with postmarket use; if a serious reaction occurs, appropriate therapy should be initiated, the implant removed if needed, and the patient should not receive further treatment with SCENESSE. ¹
Skin monitoring: SCENESSE may lead to generalized increased skin pigmentation and darkening of pre-existing nevi and ephelides; a full body skin examination twice yearly is recommended to monitor pre-existing and new pigmentary lesions. ¹
The label directs that sun and light protection measures be maintained during treatment to prevent phototoxic reactions related to EPP. ¹
Pregnancy and lactation: there are no data on use in pregnant women or on presence in human milk; safety and effectiveness in pediatric patients have not been established. ¹

Implant site reaction
26 of 125 (21%) vs 12 of 119 (10%) vehicle
Adults with EPP in studies CUV039, CUV030 and CUV029, through month 6 ¹ · Most common implant site reaction was discoloration (10%); includes bruising, erythema, pain, pruritus, swelling and expelled implant
Nausea
24 of 125 (19%) vs 17 of 119 (14%) vehicle
Adults with EPP, through month 6 ¹ · Not graded in the label table
Oropharyngeal pain
9 (7%) vs 6 (5%) vehicle
Adults with EPP, through month 6 ¹ · Not graded in the label table
Cough
8 (6%) vs 4 (3%) vehicle
Adults with EPP, through month 6 ¹ · Not graded in the label table
Fatigue
7 (6%) vs 3 (3%) vehicle
Adults with EPP, through month 6 ¹ · Not graded in the label table
Skin hyperpigmentation
5 (4%) vs 0 (0%) vehicle
Adults with EPP, through month 6 ¹ · Includes lip pigmentation and pigmentation disorder
Melanocytic nevus
5 (4%) vs 2 (2%) vehicle
Adults with EPP, through month 6 ¹ · Not graded in the label table
Dizziness
5 (4%) vs 4 (3%) vehicle
Adults with EPP, through month 6 ¹ · Not graded in the label table
Hypersensitivity (urticaria, angioedema, anaphylaxis)
Postmarketing reports; frequency not estimable
Post-approval use ¹ · Serious reactions, including anaphylaxis, reported

Emerging safety signals

Serious hypersensitivity reactions, including anaphylaxis, urticaria and angioedema, were added to the label from postmarketing reports; the label's highlights list Dosage and Administration, Contraindications and Warnings and Precautions revisions dated 08/2024 (regulatory label evidence) ^1. ¹ (2024)
Because afamelanotide increases skin pigmentation, darkening of pre-existing nevi and new melanocytic nevi were reported (melanocytic nevus 4% vs 2% vehicle), and carcinogenicity studies have not been conducted (label evidence) ^1. ¹ (2026)
In a long-term antibody study of 26 patients exposed for up to 6 years, afamelanotide did not elicit new anti-drug antibodies (observational evidence) ^7. ⁷ (2015)

What is not known: The effect of renal or hepatic impairment on afamelanotide pharmacokinetics is unknown, no drug interaction studies were conducted, and the metabolic profile has not been fully characterized ^1. Carcinogenicity studies have not been conducted ^1. Safety and effectiveness in pediatric patients, and in pregnancy and lactation, have not been established ^1. The approved indication is limited to erythropoietic protoporphyria; the vitiligo trial was a single randomized study of 55 participants without a vehicle implant control ^5.

Background viewing

We haven't found a clinician video focused on Afamelanotide yet. Meanwhile, this widely watched talk covers the science of aging in general. It does not discuss Afamelanotide.

David Sinclair, PhD (Harvard Medical School) on the biology of aging

The Diary Of A CEO · 6.9M views · 2026

These creators are not affiliated with Amiravo and do not endorse Amiravo or any product linked on this site. Nothing here is medical advice. Video views counted on YouTube as of Oct 24, 2026.

Regulatory status

Status: Approved by the FDA as SCENESSE (afamelanotide) implant, NDA 210797, original approval 8 October 2019, to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria (EPP) ^1,2. In the EU it was authorised on 22 December 2014, under exceptional circumstances, for prevention of phototoxicity in adults with EPP ^3.
United States (FDA): Approved under NDA 210797 (SCENESSE, original approval 8 October 2019) per the Drugs@FDA application record ^2; the current label was reviewed from DailyMed ^1.
Sport (WADA): Afamelanotide is not named on the WADA 2026 Prohibited List ^9. Because it holds governmental approval for human therapeutic use, the S0 non-approved-substances class, which covers substances without such approval, does not describe it ^9.

Status varies by country and changes over time. How we describe regulatory status.

Quality and testing notes

The approved product is a finished implant, not a powder: afamelanotide acetate admixed with poly(DL-lactide-co-glycolide) in a sterile bioresorbable rod, with the peptide content stated as 16 mg afamelanotide (equivalent to 18 mg afamelanotide acetate) [1]. For any afamelanotide reference material, a certificate of analysis would typically show HPLC purity with chromatogram, identity by mass spectrometry against the anhydrous free-base molecular weight of 1646.85 stated in the label, acetate counter-ion content (the label gives 3 to 4 acetate equivalents), net peptide content and, for material intended for sterile handling, endotoxin and sterility testing [1]. Because the D-Phe7 and Nle4 substitutions do not change nominal mass relative to some isomers, chiral or orthogonal methods add confidence in identity.

How purity testing works · Reading a certificate of analysis

Check a Afamelanotide certificate of analysis against its expected mass (1,646.8 Da)

Storage and handling

Per the FDA label, SCENESSE implants are stored in a refrigerator at 2 to 8 degrees C (36 to 46 degrees F) and protected from light [1]. Research material should be handled according to the supplier's documentation.

Frequently asked questions

Is afamelanotide FDA-approved?

Yes. It is approved as SCENESSE implant (NDA 210797, 2019) to increase pain-free light exposure in adults with a history of phototoxic reactions from erythropoietic protoporphyria ^1,2.

Is afamelanotide the same as Melanotan I?

Afamelanotide is the INN for [Nle4, D-Phe7]-alpha-MSH, and PubChem lists 'Melanotan' among its synonyms ^8. Melanotan II is a different, cyclic peptide.

How does afamelanotide work?

It is an alpha-MSH analogue that binds predominantly to MC1-R and increases eumelanin production in the skin independently of sunlight or UV exposure ^1.

What did the pivotal trials measure?

Hours spent in direct sunlight on days without phototoxic pain; in CUV039 the median over 180 days was 64.1 hours with afamelanotide versus 40.5 hours with vehicle per the label ^1.

What adverse reactions are listed on the label?

The most common (more than 2%) were implant site reaction, nausea, oropharyngeal pain, cough, fatigue, dizziness, skin hyperpigmentation, somnolence, melanocytic nevus, respiratory tract infection, non-acute porphyria and skin irritation; postmarketing hypersensitivity including anaphylaxis has been reported ^1.

What is its half-life?

The label gives an apparent half-life of approximately 15 hours from the controlled-release implant ^1.

Is afamelanotide approved in Europe?

Yes, the EU authorised Scenesse in December 2014 under exceptional circumstances for prevention of phototoxicity in adults with EPP ^3.

Latest indexed research

No new studies were filed in the last sweep.

Search all studies on Afamelanotide (PubMed, Europe PMC, ClinicalTrials.gov)

Listed by publication type from the index record. Inclusion is not an endorsement; open the source to read the findings.

Revision history

Meaningful changes to this entry, with dates and sources. Last reviewed Oct 23, 2026. Typo and layout fixes are not listed.

New section· Schedules by time periodOct 23, 2026
Added week-by-week schedules from the FDA label (1 group, 1 arms).
Source: SCENESSE (afamelanotide) implant, for subcutaneous use - prescribing information

References

SCENESSE (afamelanotide) implant, for subcutaneous use. Prescribing information, CLINUVEL Inc. (SPL published May 13, 2026) DailyMed (FDA label). 2026
Drugs@FDA application record for SCENESSE (afamelanotide), NDA 210797, original approval 8 October 2019 openFDA / Drugs@FDA. 2026
Scenesse (afamelanotide): EPAR, medicine overview (authorised 22 December 2014 under exceptional circumstances) European Medicines Agency. 2026
Afamelanotide for Erythropoietic Protoporphyria N Engl J Med. 2015
Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial JAMA Dermatol. 2015
Pharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders Clin Pharmacokinet. 2017
Evaluation of the immunogenicity of the synthetic alpha-melanocyte-stimulating hormone (alpha-MSH) analogue afamelanotide ([Nle4-D-Phe7]-alpha-MSH, Scenesse) in erythropoietic protoporphyria patients by ELISA detecting both anti-afamelanotide and anti-alpha-MSH antibodies Skin Pharmacol Physiol. 2015
PubChem compound record for afamelanotide (CID 16197727; CAS 75921-69-6) PubChem. 2026
International Standard: Prohibited List 2026 World Anti-Doping Agency. 2026

Last reviewed October 23, 2026 by the Amiravo editorial team.

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Specifications

Molecular formula: C₇₈H₁₁₁N₂₁O₁₉
Molecular weight: 1,646.8 g/mol
CAS number: 75921-69-6
PubChem CID: 16197727
DrugBank: DB04931
Sequence: Ac-Ser-Tyr-Ser-Nle-Glu-His-D-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2
Format: Lyophilized vial
Type: Single compound

Identifiers from PubChem. Verify against the supplier’s documentation for your lot.

Research stats

How much has been published, not how good it is.

PubMed records: 297
Indexed as human research: 172
Animal-only research: 84
Randomized controlled trials: 5
Registered trials: 23
Trials with posted results: 12
FDA adverse-event reports (FAERS): 19
NIH-funded projects naming it: 22

PubMed records per year (current year is partial).

Counts from title/abstract searches of PubMed, ClinicalTrials.gov, openFDA and NIH RePORTER, checked 2026-10-24. Names shared with other substances can inflate counts. FAERS reports are spontaneous and do not establish cause. Funding shows interest, not evidence. Method

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