Melanotan-1 (Afamelanotide)
/ Synthetic alpha-MSH analog; cyclic 13-residue peptide; MC1R-selective melanocortin agonistALIAS · Afamelanotide · Scenesse (trade — Clinuvel) · MT-I · Melanotan-1 · Melanotan I
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Tier 1. Afamelanotide (Scenesse, Clinuvel Pharmaceuticals) was FDA-approved in 2019 for the prevention of phototoxicity in adults with erythropoietic protoporphyria (EPP) — the first approved melanocortin therapeutic. Approved as a long-acting subcutaneous controlled-release implant. Phase 3 RCTs in EPP (Langendonk 2015 NEJM) supported the approval. Vendor-sold 'melanotan-1' research powder is not pharmaceutically equivalent to Scenesse and has no human use approval.
Afamelanotide is a synthetic linear 13-residue analog of alpha-melanocyte-stimulating hormone (alpha-MSH) with two key substitutions — the methionine at position 4 replaced by norleucine (Nle) and the L-phenylalanine at position 7 replaced by D-phenylalanine — that confer markedly increased metabolic stability and prolonged receptor activation compared with native alpha-MSH. The peptide is a melanocortin-receptor agonist with relative selectivity for MC1R, the receptor expressed on epidermal melanocytes; agonism stimulates eumelanogenesis, increasing melanin synthesis and skin pigmentation. In erythropoietic protoporphyria, the increased melanin acts as an optical filter that reduces accumulated photon dose to porphyrin-loaded skin and so reduces phototoxic pain on light exposure.
Tier 1. The Phase 3 EU/US trial (Langendonk 2015 NEJM) randomised approximately 168 EPP patients to subcutaneous afamelanotide controlled-release implants every two months versus placebo and reported increased pain-free sun exposure time and improved quality-of-life measures. Italian/Swiss observational and earlier Phase 2 work (Biolcati 2014) also supported the EPP indication. Other clinical investigations have included vitiligo (combination with narrowband UVB) and Hailey-Hailey disease, with smaller datasets.
In the Scenesse EPP trial database the most common adverse events were nausea, headache, fatigue, implant-site reactions (haematoma, pain, erythema), and skin pigmentation changes including new naevi and darkening of existing naevi. Long-term registry surveillance for melanoma and other dermatological neoplasia is ongoing as a post-marketing requirement. The implant is administered every two months by trained healthcare providers.
Regulatory status
- FDA status:
- FDA-approved
- Compounding:
- Not eligible for compounding (approved, not in shortage)
The most important practical distinction for an evidence site: vendor-sold 'melanotan-1' research powder marketed for self-injected tanning is not the same product as Scenesse, and the vendor material has no Phase 3 safety database, no controlled formulation, and no monitoring framework. The combination of MC1R agonism, sustained dosing, and the recognised acceleration of new naevi has driven public-health concerns about over-the-counter melanotan-1 use; case reports of dysplastic and atypical naevi following recreational melanotan use exist in dermatology literature but are not rigorously aggregated. Melanotan-1 (afamelanotide) and melanotan-2 are pharmacologically distinct (different sequences, different receptor selectivity profiles) and should not be conflated.