# Afamelanotide - Canonical: https://residue.info/c/afamelanotide/ - Also called: Melanotan I, MT-I, Melanotan 1, Scenesse, CUV1647 - Evidence grade: A (Approved / regulatory-grade). FDA-approved (Scenesse, NDA 210797) for erythropoietic protoporphyria on the basis of randomized, placebo-controlled trials. Other uses are graded separately. - Status: FDA-approved (Scenesse implant) · Prescription - PubChem CID: 16197727 - Updated: 2026-10-19 · Reviewed by: Residue Editorial Team Afamelanotide is a synthetic α-melanocyte-stimulating hormone analog and first-in-class melanocortin-1 receptor agonist [1], first synthesized in 1980 [2]. In two randomized, double-blind trials in erythropoietic protoporphyria (EPP), a 16 mg implant every 60 days increased the time patients could spend in direct sunlight without pain [3]. FDA approved it as the Scenesse subcutaneous implant in October 2019 [4]. ## Key findings - In the US trial (94 patients), median pain-free time in direct sunlight over 6 months was 69.4 hours with afamelanotide versus 40.8 hours with placebo (P=0.04) [3]. (anchor: https://residue.info/c/afamelanotide/#kf-pmid-26132941) - In the EU trial (74 patients), median pain-free time was 6.0 versus 0.8 hours (P=0.005), and phototoxic reactions numbered 77 versus 146 [3]. (anchor: https://residue.info/c/afamelanotide/#kf-pmid-26132941-2) - In 26 US clinic patients given at least two implants, median time to symptom onset in sunlight rose from 12.5 to 120 minutes, without improvement in protoporphyrin levels or liver tests [5]. (anchor: https://residue.info/c/afamelanotide/#kf-pmid-38929673) - Subcutaneous dosing had full bioavailability; oral and transdermal dosing produced no measurable plasma levels or pigmentation [2]. (anchor: https://residue.info/c/afamelanotide/#kf-pmid-28063031) - Common adverse events were headache, fatigue, nausea and implant-site reactions [1][6]. (anchor: https://residue.info/c/afamelanotide/#kf-pmid-26979527) ## Effects by system - Erythropoietic protoporphyria (light tolerance) (grade A): Longer pain-free sunlight exposure and fewer phototoxic reactions versus placebo in two RCTs [3]. (anchor: https://residue.info/c/afamelanotide/#effect-erythropoietic-protoporphyria-light-tolerance) - Quality of life (EPP) (grade A): Improved on validated questionnaires in both trials and in a US clinic cohort [3][5]. (anchor: https://residue.info/c/afamelanotide/#effect-quality-of-life-epp) - Skin pigmentation (volunteers) (grade C): Ten daily SC doses produced long-lasting pigmentation, including in fair skin and MC1R variants [2]. (anchor: https://residue.info/c/afamelanotide/#effect-skin-pigmentation-volunteers) - Other skin disorders (grade C): Reported results in polymorphic light eruption, solar urticaria, Hailey-Hailey disease and vitiligo [2]. (anchor: https://residue.info/c/afamelanotide/#effect-other-skin-disorders) ## What is afamelanotide? Afamelanotide is a synthetic analog of α-melanocyte-stimulating hormone. It was synthesized in 1980 and was the first α-MSH analog given to human volunteers, chosen because it is more active and stable than the natural hormone [2]. PubChem lists the formula C78H111N21O19 [7]. It is marketed as Scenesse, a 16 mg biodegradable implant [1]. ## How does afamelanotide work? It binds the melanocortin-1 receptor. MC1R signaling increases melanin synthesis, induces antioxidant activity, enhances DNA repair and modulates inflammation [2]. It can activate eumelanin production without UV exposure [6]. In volunteers, neither MC1R variants nor fair skin reduced the pigmentation response [2]. ## What have studies found? **Erythropoietic protoporphyria.** EPP is an inherited disorder of heme synthesis in which light causes severe burning pain [6]. Two multicenter, randomized, double-blind, placebo-controlled trials tested the 16 mg implant every 60 days. In the US trial, median pain-free time in direct sunlight over six months was 69.4 hours versus 40.8 hours on placebo; in the EU trial it was 6.0 versus 0.8 hours over nine months, with fewer phototoxic reactions. Quality of life improved in both [3]. **Real-world use.** At the Massachusetts General Hospital porphyria center, 29 adults received afamelanotide in 2021–2022. Among the 26 with at least two implants, median time to symptoms in sunlight rose from 12.5 to 120 minutes. Protoporphyrin levels and liver tests did not improve [5]. **Registered trials.** ClinicalTrials.gov lists studies in EPP, vitiligo, polymorphic light eruption, acne and other conditions [8]. ## What is its safety record? In the phase III trial CUV039, no drug-related serious adverse events were reported; headache and implant-site reactions were common [1]. A 2017 review reported no late effects in volunteers 25 years after first exposure or in EPP patients treated for up to 8 years, and that an immunogenic potential had been excluded [2]. Drugs@FDA lists Scenesse (afamelanotide) subcutaneous implant with an original approval on October 8, 2019 and prescription marketing status [4]. Approval covers its labeled use in EPP. Afamelanotide is not on FDA's compounding-risk lists [9]. ## What is still unknown? - **Dosing interval.** The 60-day interval was not based on effectiveness studies, and one review suggests four implants a year may be insufficient for some patients [6]. - **Other indications** such as vitiligo rely on smaller studies [2]. - **Unregulated 'melanotan' products** are a separate problem: case reports link them to changing moles, new dysplastic naevi and four melanomas, without conclusive evidence of cause [10]. ## Frequently asked questions **Is afamelanotide the same as Melanotan 1?** Afamelanotide is the α-MSH analog first synthesized in 1980 and given to volunteers [2], and PubChem lists 'Melanotan' among its synonyms [7]. Products sold online as 'melanotan I' are unregulated and untested; a 2017 review contrasts them with the approved, tested afamelanotide [10]. **Is afamelanotide FDA-approved?** Yes, as Scenesse, a subcutaneous implant with an original approval date of October 8, 2019 [4]. Its approved use is preventing phototoxicity in erythropoietic protoporphyria, not cosmetic tanning [6]. **How is afamelanotide given?** As a biodegradable controlled-release implant containing 16 mg, placed under the skin [1]; the trials used one implant every 60 days [3]. **What is the difference between Melanotan 1 and Melanotan 2?** Afamelanotide (Melanotan I) is approved and has randomized trials behind it [3][4]. Melanotan II is a shorter cyclic analog that was never approved; its controlled human data are three small studies [11][12]. ## Sources [1] Afamelanotide: A Review in Erythropoietic Protoporphyria. Kim ES & Garnock-Jones KP Am J Clin Dermatol. 2016. https://pubmed.ncbi.nlm.nih.gov/26979527/ [2] Pharmacokinetics and Pharmacodynamics of Afamelanotide and its Clinical Use in Treating Dermatologic Disorders. Minder EI et al. Clin Pharmacokinet. 2017. https://pubmed.ncbi.nlm.nih.gov/28063031/ [3] Afamelanotide for Erythropoietic Protoporphyria. Langendonk JG et al. N Engl J Med. 2015. https://pubmed.ncbi.nlm.nih.gov/26132941/ [4] Drugs@FDA: SCENESSE (NDA210797). CLIVUNEL INC; original approval 2019-10-08; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=210797 [5] Afamelanotide for Treatment of the Protoporphyrias: Impact on Quality of Life and Laboratory Parameters in a US Cohort. Leaf RK et al. Life (Basel). 2024. https://pubmed.ncbi.nlm.nih.gov/38929673/ [6] Afamelanotide for prevention of phototoxicity in erythropoietic protoporphyria. Wensink D et al. Expert Rev Clin Pharmacol. 2021. https://pubmed.ncbi.nlm.nih.gov/33507118/ [7] PubChem compound record: Afamelanotide. C78H111N21O19 · MW 1646.8 g/mol. https://pubchem.ncbi.nlm.nih.gov/compound/16197727 [8] ClinicalTrials.gov registry search: afamelanotide OR CUV1647. 23 registered studies at fetch. https://clinicaltrials.gov/search?intr=afamelanotide%20OR%20CUV1647 [9] Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. U.S. FDA, content current as of 04/22/2026. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks [10] Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Habbema L et al. Int J Dermatol. 2017. https://pubmed.ncbi.nlm.nih.gov/28266027/ [11] Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Dorr RT et al. Life Sci. 1996. https://pubmed.ncbi.nlm.nih.gov/8637402/ [12] Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: double-blind, placebo controlled crossover study. Wessells H et al. J Urol. 1998. https://pubmed.ncbi.nlm.nih.gov/9679884/ --- From Residue. Research and education only; not medical advice. Quote with attribution and a link to the canonical page.