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Afamelanotide
Melanotan I made into a medicine: a two-monthly implant that lets people with EPP tolerate more light
Afamelanotide is [Nle4, D-Phe7]-α-MSH, the melanotan I of early tanning research, a long-lasting copy of the hormone that drives skin pigment. As Scenesse, a 16 mg implant placed under the skin every two months, it was approved in the US in 2019 to increase pain-free light exposure in adults with erythropoietic protoporphyria.
What is it?
In erythropoietic protoporphyria, a pigment precursor builds up in the skin and sunlight triggers burning pain within minutes. Afamelanotide, the [Nle4, D-Phe7] analogue of α-MSH once called melanotan I, does not treat the porphyrin build-up; it activates the melanocortin-1 receptor on melanocytes, raising eumelanin in the skin and the dose of light it takes to cause a reaction.
The pivotal trials measured hours in the sun. In 94 US patients over six months, median pain-free time in direct sunlight was 69.4 hours on the implant against 40.8 on placebo; in 74 EU patients over nine months it was 6.0 against 0.8 hours, and phototoxic reactions fell from 146 to 77. The gains were real but modest in absolute terms, and the label still requires sun protection.
Clinic cohorts report larger changes in what patients can do. In 117 Dutch patients followed for two years, 98% stayed on treatment and time outside rose by 6.1 hours a week. In Switzerland the longest reaction-free time in sun went from a median 10 minutes to 180, and at a US centre the time to symptoms went from 12.5 minutes to 120. These studies compare patients with themselves before treatment, without a placebo group.
The liver is a second question. Protoporphyria can damage the liver, and in a Swiss cohort liver tests improved as the number of implants rose, though a US cohort saw no change in protoporphyrin or liver tests; the label makes no liver claim.
Two practical questions have answers. Moles darken during treatment, but dermoscopy of 103 moles found the changes reversible, with no signs suggesting malignancy and no new moles. And because patients avoid sun, vitamin D stays low: in 230 patients the implant did not raise it, while supplements did.
The medicine is a 16 mg implant placed under the skin every two months. Injected melanotan I is rapidly cleared, with a half-life of 0.8 to 1.7 hours in a 1997 volunteer study, against about 15 hours from the implant. Because it darkens skin, moles and freckles, the label recommends a full-body skin examination twice a year.
Uses beyond protoporphyria are unapproved. Added to narrowband UV-B, a monthly implant sped repigmentation in vitiligo (48.6% against 33.3% at day 168).
Only the Scenesse implant is approved; melanotan I sold in any other form, including injections, is not, and melanotan II is a different, unapproved peptide.
Mechanism of Action
Afamelanotide raises the skin's own pigment so that more light is needed to trigger pain.
MC1R agonist
Selective agonist at the melanocortin-1 receptor on melanocytes, raising tyrosinase activity (dataset mechanism).
Eumelanin
More eumelanin absorbs and dissipates UV and visible light (dataset mechanism).
Slow-release implant
Half-life about 15 hours from the implant, against 0.8-1.7 hours after injection (label 12.3; 1997 study).
Published Research
The studies behind afamelanotide, read from their PubMed abstracts: the pivotal US and EU trials, Dutch, Swiss and US clinic cohorts, a liver-test analysis, early volunteer pharmacokinetics and a vitiligo trial. Dosing from the Scenesse label read September 30, 2026.
The pivotal EPP trials
In trials of 94 US and 74 EU patients with an implant every 60 days, median pain-free time in direct sun was 69.4 against 40.8 hours (US, six months) and 6.0 against 0.8 hours (EU, nine months); EU phototoxic reactions fell from 146 to 77. Quality of life improved and adverse events were mostly mild.
Two years in Dutch practice
In 117 patients treated at Erasmus MC for a median of 2 years, 98% stayed on treatment; time outside rose by 6.1 hours a week, quality of life by 14%, and reactions were less painful, though their number and length did not change.
Swiss cohort: light tolerance
In 39 Swiss patients, the longest time in sunlight without a reaction rose from a median 10 minutes before treatment to 180 minutes on it, the worst reaction's pain fell from 10 to 6 out of 10, and adherence was 97.4%.
US cohort: minutes to symptoms
In 29 patients at a US porphyria centre, median time to symptoms in sunlight rose from 12.5 minutes before treatment to 120 minutes on it, quality of life improved, and protoporphyrin and liver tests did not change.
Liver tests and dose
Across 2,933 liver tests and 1,659 implants in 70 Swiss patients, ALT and bilirubin fell as the number of implants in the past year rose, and protoporphyrin rose with days since the last implant, a dose-dependent association in an observational study.
Melanotan I in volunteers
In three men given melanotan I by vein, mouth and under the skin, the subcutaneous dose was fully absorbed, nothing was detectable after oral dosing, and the elimination half-life was 0.8 to 1.7 hours; the skin darkened.
Vitiligo with UV-B light
In 55 adults with vitiligo, adding a monthly 16 mg implant to narrowband UV-B gave faster repigmentation of face and arms and 48.6% repigmentation at day 168 against 33.3% with light alone. This use is not approved.
Vitamin D
Across 230 patients and 1,774 measurements, vitamin D deficiency stayed common on afamelanotide (71.8% below 50 nmol/L); the implant alone did not raise levels, while cholecalciferol supplements did.
What happens to moles
In 15 patients with 103 moles followed by dermoscopy, the implant caused reversible thickening of the pigment network and more globules, with no changes suggesting malignancy and no new moles.
Acute stroke: a first safety study
In six people with acute ischaemic stroke ineligible for clot removal, 16 mg implants were tolerated; one died of a recurrent stroke judged unrelated, and NIHSS improved from 6 to 2 by day 7 in survivors, without a control group.
Approval in Europe
A drug review describing afamelanotide as the first melanocortin-1 receptor agonist, approved in the EU for preventing phototoxicity in adults with EPP as a 16 mg controlled-release implant, on the strength of improved light tolerance in phase III.
Dosing Data
Dosed by label: one implant inserted above the hip by a professional trained in the procedure.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Scenesse label (version 11).
Contraindications & Cautions
From the label.
Legal Status
Approved in the US and the EU for one disease.
Frequently Asked Questions
?Is afamelanotide the same as melanotan I?
Yes, chemically: both names describe [Nle4, D-Phe7]-α-MSH. The approved medicine is the Scenesse implant; no other form of it is approved.
?Does it cure EPP?
No. It raises the light needed to trigger pain; patients in the trials still needed sun protection.
?How is it different from melanotan II?
Melanotan II is a different, cyclic peptide that also acts on other melanocortin receptors; it has no approval.
?How much does it help in daily life?
In a two-year Dutch cohort, patients spent 6.1 more hours a week outside; Swiss patients' longest reaction-free time rose from 10 to 180 minutes, though without a placebo comparison.
?Does it protect the liver?
Unproven. One Swiss cohort found liver tests improved with more implants, while a US cohort saw no change; the label makes no liver claim.
?How often is the implant given?
Every two months, as a 16 mg implant placed under the skin.
?Why are skin checks needed?
It darkens skin, existing moles and freckles, so the label recommends a full-body skin examination twice a year.
?Is it used for vitiligo?
Not under its label; a trial adding it to UV-B light sped repigmentation, but that use is unapproved.
?Do patients still need vitamin D?
Often. In 230 patients, deficiency stayed common on afamelanotide, and only cholecalciferol supplements raised vitamin D levels.
?Has it been tried outside skin disease?
A six-patient safety study in acute stroke found it tolerated; there is no evidence it helps stroke.
References
- [fda-pi] Scenesse (afamelanotide) implant US prescribing information (DailyMed version 11, effective May 11, 2026); read September 30, 2026.
- [clinical-trial] Langendonk JG, et al. "Afamelanotide for Erythropoietic Protoporphyria." N Engl J Med, 2015;373(1):48-59. PMID: 26132941.
- [pubmed] Ugwu SO, et al. "Skin pigmentation and pharmacokinetics of melanotan-I in humans." Biopharm Drug Dispos, 1997;18(3):259-69. PMID: 9113347.
- [clinical-trial] Lim HW, et al. "Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial." JAMA Dermatol, 2015;151(1):42-50. PMID: 25230094.
- [review] Kim ES, et al. "Afamelanotide: A Review in Erythropoietic Protoporphyria." Am J Clin Dermatol, 2016;17(2):179-85. PMID: 26979527.
- [pubmed] Wensink D, et al. "Association of Afamelanotide With Improved Outcomes in Patients With Erythropoietic Protoporphyria in Clinical Practice." JAMA Dermatol, 2020;156(5):570-575. PMID: 32186677.
- [pubmed] Barman-Aksözen J, et al. "Increased phototoxic burn tolerance time and quality of life in patients with erythropoietic protoporphyria treated with afamelanotide - a three years observational study." Orphanet J Rare Dis, 2020;15(1):213. PMID: 32811524.
- [pubmed] Leaf RK, et al. "Afamelanotide for Treatment of the Protoporphyrias: Impact on Quality of Life and Laboratory Parameters in a US Cohort." Life (Basel), 2024;14(6). PMID: 38929673.
- [pubmed] Minder AE, et al. "Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage Related to Erythropoietic Protoporphyria." Life (Basel), 2023;13(4). PMID: 37109595.
- [pubmed] Kluijver LG, et al. "The effects of cholecalciferol and afamelanotide on vitamin D levels in erythropoietic protoporphyria: a multicentre cohort study." Br J Dermatol, 2024;191(3):357-364. PMID: 38634774.
- [pubmed] Arisi M, et al. "Clinical and dermoscopic changes of acquired melanocytic nevi of patients treated with afamelanotide." Photochem Photobiol Sci, 2021;20(2):315-320. PMID: 33721252.
- [pubmed] Stanislaus V, et al. "A feasibility and safety study of afamelanotide in acute stroke patients - an open label, proof of concept, phase iia clinical trial." BMC Neurol, 2023;23(1):281. PMID: 37496004.
Sources & Citations
Dosing and warnings from the Scenesse label (DailyMed version 11, read September 30, 2026); approval from Drugs@FDA; studies from PubMed abstracts.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.