{"id":"afamelanotide","name":"Afamelanotide (Melanotan I)","aliases":["Melanotan I","Melanotan-1","Scenesse","CUV1647","NDP-MSH"],"url":"https://lyoresearch.com/compounds/afamelanotide","class":{"id":"melanocortins","name":"Melanocortin agonists","url":"https://lyoresearch.com/classes/melanocortins"},"summary":"Afamelanotide is a linear analogue of the pigment hormone α-MSH, developed in the 1980s as the first 'Melanotan'. It is an approved medicine — as a subcutaneous implant replaced every two months — for erythropoietic protoporphyria, a genetic disorder in which sunlight causes severe pain within minutes. In two randomised trials it roughly doubled the hours patients could spend in direct sun without pain. The same molecule is sold illegally as a tanning injection; for that use there is no approval and no controlled evidence of safety.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"2 phase 3 RCTs (n=168) + long-term registry data","regulatory_status":"Approved (Rx) — erythropoietic protoporphyria","molecule":{"formula":"C78H111N21O19","molecular_weight":"1646.8","cas":"75921-69-6","pubchem_cid":16197727,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous implant, every 2 months","half_life":"About 15 hours (apparent, from implant)","licensed_regimen":"Single 16 mg implant inserted subcutaneously every 2 months","product":"Scenesse","source":{"title":"Scenesse prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94f53286-11dd-7fbb-e053-2a95a90a7c48"}},"outcomes":[{"outcome":"Pain-free sun exposure in erythropoietic protoporphyria","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"2 phase 3 RCTs (EU n=74, US n=94)","evidence":"In both trials patients on afamelanotide implants spent significantly longer in direct sunlight without pain; the EU trial also counted fewer phototoxic reactions. Quality of life improved in both.","references":[{"citation":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","where":"N Engl J Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/"}],"verbatim":{"text":"In the U.S. study, the duration of pain-free time after 6 months was longer in the afamelanotide group (median, 69.4 hours, vs. 40.8 hours in the placebo group; P=0.04).","citation":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/"}},{"outcome":"Skin pigmentation (tanning)","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"Early trials + the phase 3 programme","evidence":"It darkens skin reliably — that is its mechanism, and hyperpigmentation is the expected effect in every trial. What has never been studied is the safety of using it for cosmetic tanning in healthy people, and no regulator has approved that use.","references":[{"citation":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","where":"N Engl J Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/"}]},{"outcome":"Vitiligo repigmentation","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Small RCTs with phototherapy","evidence":"Small trials combining the implant with narrowband UVB reported faster repigmentation than phototherapy alone. Not an approved indication.","references":[{"citation":"Afamelanotide with narrowband UV-B phototherapy for vitiligo — randomised trials.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=afamelanotide+vitiligo+randomized+narrowband"}]},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":true,"human_studies":"Phase 3 + registry","evidence":"Nausea, headache and implant-site reactions; darkening of skin and moles, which requires skin monitoring on treatment. Serious events in the trials were not judged drug-related.","references":[{"citation":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","where":"N Engl J Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/"}],"verbatim":{"text":"Adverse events were mostly mild; serious adverse events were not thought to be related to the study drug.","citation":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Centrally authorised (Scenesse) in 2014 under exceptional circumstances for erythropoietic protoporphyria. Tanning use is not authorised; injectable 'Melanotan' products are illegal."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved October 2019 for erythropoietic protoporphyria, implant only."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Licensed for erythropoietic protoporphyria. The MHRA has repeatedly warned against injectable tanning products."},{"region":"Australia","status":"Registered, prescription-only","note":"On the ARTG for erythropoietic protoporphyria; the developer is Australian."},{"region":"Canada","status":"Not authorised","note":"LYO found no Health Canada authorisation at review."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the Prohibited List."}],"faq":[{"q":"Is Melanotan I the same as Melanotan II?","a":"No. Melanotan I is linear and selective for the pigment receptor; Melanotan II is cyclic and hits several melanocortin receptors, which is why it also causes erections and nausea. Melanotan I became an approved medicine; Melanotan II did not."},{"q":"Can you get afamelanotide for tanning?","a":"Not lawfully. It is approved only for erythropoietic protoporphyria, as an implant placed by a clinician. The injectable 'Melanotan I' sold online is an unlicensed product of unknown content."},{"q":"Does it cause skin cancer?","a":"Unknown; it is the main open safety question. It darkens moles, so treated patients have regular skin checks. Registry data over years of licensed use have not shown an excess so far."}],"references":[{"cite":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","where":"N Engl J Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/","note":"Two phase 3 trials; EU n=74, US n=94."},{"cite":"Scenesse (afamelanotide) — European public assessment report.","where":"EMA, 2014 onward","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/scenesse","note":"Licensed indication and conditions."},{"cite":"Afamelanotide with narrowband UV-B phototherapy for vitiligo — randomised trials.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=afamelanotide+vitiligo+randomized+narrowband","note":"Small trials; not an approved indication."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade A for erythropoietic protoporphyria on two phase 3 RCTs."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}