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Melanotan I (Afamelanotide)

Afamelanotide ([Nle4, D-Phe7]-alpha-MSH)

PhotoprotectionEPP treatmentEumelanin stimulation13 amino acids

What it is

A synthetic 13 amino acid linear analog of alpha-melanocyte-stimulating hormone (alpha-MSH), approved in the US, EU, and Australia as Scenesse for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP). Afamelanotide is a selective MC1R agonist that stimulates eumelanin production independent of UV exposure, providing systemic photoprotection. Substitutions at positions 4 (norleucine) and 7 (D-phenylalanine) confer approximately 4-fold greater MC1R potency and significantly improved enzymatic stability compared to native alpha-MSH. It is administered as a bioresorbable subcutaneous implant by a healthcare professional.

Community-reported ranges

Dosing and side effects sourced from FDA prescribing information (NDA 210797) and EMA SmPC. Clinical data from published phase III trials. Not dosing guidance.

Reported dose range

1600016000 mcg

Estimated half-life

~30 min (intrinsic peptide); ~15 hours (apparent, from sustained-release implant)

Source: FDA prescribing information (NDA 210797) and EMA SmPC

Reported cycle length

852 weeks on

Per label: implant every 60 days; year-round use approved in EU (2025) and US weeks off

Route

subcutaneous_implant

Common vial sizes

16mg implant

Reported timing

Implant administered every 60 days; no specific daily timing

Reported frequency

One 16mg subcutaneous implant every 60 days, administered by a healthcare professional

Frequently discussed alongside

Based on community forum discussions. Not a recommendation to combine compounds.

Published research

Afamelanotide was evaluated in multiple phase II and III clinical trials for EPP. The pivotal phase III trial (Langendonk et al., NEJM 2015) demonstrated a significant increase in pain-free time in direct sunlight (median 69.4 hours vs. 40.8 hours placebo over 6 months, p=0.005). The drug has 4-fold greater MC1R potency than native alpha-MSH with an extended duration of action via bioresorbable implant. Peak plasma levels (~3.7 ng/mL) occur at ~36 hours post-implant; >90% of drug is released by day 5. The EMA initially restricted use to seasonal months but approved year-round treatment in September 2025. Investigational applications include vitiligo, polymorphic light eruption, and xeroderma pigmentosum.

Reported side effects

From community self-reports. Not from controlled studies.

Per FDA/EMA prescribing information: implant site reactions (21%, including bruising, erythema, pain, swelling), nausea (~19%), headache (~20%), fatigue, dizziness, somnolence, abdominal pain, diarrhea, vomiting, flushing, generalized skin darkening, darkening or appearance of new nevi, oropharyngeal pain, cough, and musculoskeletal pain. Postmarketing: rare anaphylaxis. Skin examinations every 6 months are recommended due to changes in moles and pigmentation. Contraindicated in severe hepatic impairment or hepatic porphyria.

Regulatory status

FDA (United States)

FDA-approved (October 8, 2019). NDA 210797. Marketed as Scenesse for EPP in adults. Orphan Drug and Priority Review designations. Approved only for EPP — not for tanning, photoprotection in healthy individuals, or any other indication.

Health Canada

Not yet authorized. CLINUVEL filed a New Drug Submission (NDS) on October 1, 2024; review is ongoing as of March 2026.

WADA (Competitive Athletes)

Not explicitly named on the WADA Prohibited List, but as a synthetic alpha-MSH analog it is likely captured under S2 (Peptide Hormones) catch-all provisions. Athletes with EPP would require a Therapeutic Use Exemption (TUE).

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