Melanotan I (afamelanotide)
Afamelanotide is an FDA-approved 16 mg controlled-release implant for increasing pain-free light exposure in adults with erythropoietic protoporphyria. That product and indication do not validate cosmetic tanning with an unapproved vial, nasal product, or free peptide.
synthetic alpha-MSH analog
- Also called afamelanotide
- Thirteen-amino-acid alpha-MSH analog
- Scenesse is a controlled-release implant for EPP
- Cosmetic tanning is outside the approved indication
What exactly is Melanotan I?
Melanotan I is afamelanotide, a 13-amino-acid analog of alpha-melanocyte-stimulating hormone. The approved product is Scenesse, a 16 mg controlled-release implant; free peptide sold in a vial is not that finished product.
FDA label · EPP implant evidence
FDA prescribing information
US Food and Drug Administration, NDA 210797, 2019.
Scenesse is a 16 mg subcutaneous controlled-release implant for adults with erythropoietic protoporphyria. In CUV039, 93 participants received three implants over 180 days; median pain-free direct-sunlight time was 64.1 hours with afamelanotide and 40.5 with vehicle. CUV029 enrolled 74 participants, used five implants over 270 days, and measured a different sunlight window.
- Participants / model
- Adults with a history of phototoxic reactions from erythropoietic protoporphyria
- Treatment
- 16 mg controlled-release implant every two months
- Follow-up
- 180 days in CUV039; 270 days in CUV029
- Study design
- FDA label summarizing randomized vehicle-controlled trials
The label does not approve cosmetic tanning or an immediately released vial.
Read the original sourceThree-person PK study · oral exposure absent
Human crossover pharmacokinetic study
Ugwu SO et al. European Journal of Pharmaceutical Sciences, 1997.
Three healthy men received afamelanotide by several routes. The investigators detected exposure after intravenous and subcutaneous dosing but not after oral administration; the reported beta half-life was about 0.8 to 1.7 hours in this tiny study.
- Participants / model
- 3 healthy male volunteers
- Treatment
- Intravenous, subcutaneous, intramuscular, intranasal, and oral administration in crossover periods
- Study design
- Open crossover pharmacokinetic study
Three people cannot define efficacy or uncommon safety, and the free-peptide PK does not describe the controlled-release implant.
Read the original sourceWhat benefit has afamelanotide actually shown?
Randomized trials support increased pain-free direct-sunlight exposure in adults with erythropoietic protoporphyria using the controlled-release implant. The evidence does not establish a medical benefit from cosmetic tanning use.
How many people were in the pivotal trials?
CUV039 enrolled 93 people, split 48 active and 45 vehicle. CUV029 separately enrolled 74, split 38 active and 36 vehicle. Those are separate trial totals, not one combined 93-person program.
FDA label · EPP implant evidence
FDA prescribing information
US Food and Drug Administration, NDA 210797, 2019.
Scenesse is a 16 mg subcutaneous controlled-release implant for adults with erythropoietic protoporphyria. In CUV039, 93 participants received three implants over 180 days; median pain-free direct-sunlight time was 64.1 hours with afamelanotide and 40.5 with vehicle. CUV029 enrolled 74 participants, used five implants over 270 days, and measured a different sunlight window.
- Participants / model
- Adults with a history of phototoxic reactions from erythropoietic protoporphyria
- Treatment
- 16 mg controlled-release implant every two months
- Follow-up
- 180 days in CUV039; 270 days in CUV029
- Study design
- FDA label summarizing randomized vehicle-controlled trials
The label does not approve cosmetic tanning or an immediately released vial.
Read the original sourceFDA label · EPP implant evidence
FDA prescribing information
US Food and Drug Administration, NDA 210797, 2019.
Scenesse is a 16 mg subcutaneous controlled-release implant for adults with erythropoietic protoporphyria. In CUV039, 93 participants received three implants over 180 days; median pain-free direct-sunlight time was 64.1 hours with afamelanotide and 40.5 with vehicle. CUV029 enrolled 74 participants, used five implants over 270 days, and measured a different sunlight window.
- Participants / model
- Adults with a history of phototoxic reactions from erythropoietic protoporphyria
- Treatment
- 16 mg controlled-release implant every two months
- Follow-up
- 180 days in CUV039; 270 days in CUV029
- Study design
- FDA label summarizing randomized vehicle-controlled trials
The label does not approve cosmetic tanning or an immediately released vial.
Read the original sourceFDA review · benefit-risk and pooled safety
FDA regulatory review
US Food and Drug Administration, NDA 210797, 2019.
FDA reviewed three controlled EPP studies enrolling 244 adults. The review reports serious adverse events in 4% of afamelanotide recipients and 3% of vehicle recipients, with implant-site reactions and hyperpigmentation among common adverse reactions, and supported approval only for the EPP indication.
- Participants / model
- Adults in the Scenesse EPP development program
- Treatment
- Controlled-release afamelanotide implant
- Study design
- FDA integrated benefit-risk review
How does it change light tolerance?
Afamelanotide activates melanocortin-1 receptors and increases epidermal eumelanin. FDA considered that a plausible way to reduce phototoxic excitation in EPP, but added pigment is not proof of broad UV protection or prevention of skin cancer.
FDA review · benefit-risk and pooled safety
FDA regulatory review
US Food and Drug Administration, NDA 210797, 2019.
FDA reviewed three controlled EPP studies enrolling 244 adults. The review reports serious adverse events in 4% of afamelanotide recipients and 3% of vehicle recipients, with implant-site reactions and hyperpigmentation among common adverse reactions, and supported approval only for the EPP indication.
- Participants / model
- Adults in the Scenesse EPP development program
- Treatment
- Controlled-release afamelanotide implant
- Study design
- FDA integrated benefit-risk review
Does a tanning study validate cosmetic use?
A seven-person local-injection experiment produced measurable pigment at some sites. It was too small and short to establish durability, cancer protection, or long-term safety.
Seven-person tanning study · local pigment measures
Small human experiment
Barnetson RS et al. British Journal of Dermatology, 2000.
Seven volunteers received ten subcutaneous injections at assigned skin sites. Increased tanning and eumelanin were measured at some active sites. The experiment was small, short, site-specific, and did not establish long-term cosmetic benefit or safety.
- Participants / model
- 7 healthy volunteers
- Treatment
- Ten local subcutaneous injections with site controls
- Follow-up
- Short experimental course
- Study design
- Within-person controlled pigment experiment
Three-person PK study · oral exposure absent
Human crossover pharmacokinetic study
Ugwu SO et al. European Journal of Pharmaceutical Sciences, 1997.
Three healthy men received afamelanotide by several routes. The investigators detected exposure after intravenous and subcutaneous dosing but not after oral administration; the reported beta half-life was about 0.8 to 1.7 hours in this tiny study.
- Participants / model
- 3 healthy male volunteers
- Treatment
- Intravenous, subcutaneous, intramuscular, intranasal, and oral administration in crossover periods
- Study design
- Open crossover pharmacokinetic study
Three people cannot define efficacy or uncommon safety, and the free-peptide PK does not describe the controlled-release implant.
Read the original sourceWhat safety limits matter?
The approved implant has a defined label and monitored manufacturing. Unapproved products add identity, dose, sterility, and release-profile uncertainty; cosmetic exposure has no comparable long-term safety dataset.
- The label reports implant-site reactions and skin hyperpigmentation and directs periodic skin examination.
- Pigment changes can complicate monitoring of existing or new skin lesions.
- Pregnancy, chronic cosmetic exposure, and switching to immediate-release or nasal products are not answered by the pivotal implant trials.
FDA label · EPP implant evidence
FDA prescribing information
US Food and Drug Administration, NDA 210797, 2019.
Scenesse is a 16 mg subcutaneous controlled-release implant for adults with erythropoietic protoporphyria. In CUV039, 93 participants received three implants over 180 days; median pain-free direct-sunlight time was 64.1 hours with afamelanotide and 40.5 with vehicle. CUV029 enrolled 74 participants, used five implants over 270 days, and measured a different sunlight window.
- Participants / model
- Adults with a history of phototoxic reactions from erythropoietic protoporphyria
- Treatment
- 16 mg controlled-release implant every two months
- Follow-up
- 180 days in CUV039; 270 days in CUV029
- Study design
- FDA label summarizing randomized vehicle-controlled trials
The label does not approve cosmetic tanning or an immediately released vial.
Read the original sourceFDA review · benefit-risk and pooled safety
FDA regulatory review
US Food and Drug Administration, NDA 210797, 2019.
FDA reviewed three controlled EPP studies enrolling 244 adults. The review reports serious adverse events in 4% of afamelanotide recipients and 3% of vehicle recipients, with implant-site reactions and hyperpigmentation among common adverse reactions, and supported approval only for the EPP indication.
- Participants / model
- Adults in the Scenesse EPP development program
- Treatment
- Controlled-release afamelanotide implant
- Study design
- FDA integrated benefit-risk review
What is FDA approved?
Scenesse is FDA approved only as a 16 mg controlled-release implant to increase pain-free light exposure in adults with erythropoietic protoporphyria. Cosmetic tanning and other dosage forms are not that approved use.
FDA label · EPP implant evidence
FDA prescribing information
US Food and Drug Administration, NDA 210797, 2019.
Scenesse is a 16 mg subcutaneous controlled-release implant for adults with erythropoietic protoporphyria. In CUV039, 93 participants received three implants over 180 days; median pain-free direct-sunlight time was 64.1 hours with afamelanotide and 40.5 with vehicle. CUV029 enrolled 74 participants, used five implants over 270 days, and measured a different sunlight window.
- Participants / model
- Adults with a history of phototoxic reactions from erythropoietic protoporphyria
- Treatment
- 16 mg controlled-release implant every two months
- Follow-up
- 180 days in CUV039; 270 days in CUV029
- Study design
- FDA label summarizing randomized vehicle-controlled trials
The label does not approve cosmetic tanning or an immediately released vial.
Read the original sourceStudies and sources
FDA label · EPP implant evidence
FDA prescribing information
US Food and Drug Administration, NDA 210797, 2019.
Scenesse is a 16 mg subcutaneous controlled-release implant for adults with erythropoietic protoporphyria. In CUV039, 93 participants received three implants over 180 days; median pain-free direct-sunlight time was 64.1 hours with afamelanotide and 40.5 with vehicle. CUV029 enrolled 74 participants, used five implants over 270 days, and measured a different sunlight window.
- Participants / model
- Adults with a history of phototoxic reactions from erythropoietic protoporphyria
- Treatment
- 16 mg controlled-release implant every two months
- Follow-up
- 180 days in CUV039; 270 days in CUV029
- Study design
- FDA label summarizing randomized vehicle-controlled trials
The label does not approve cosmetic tanning or an immediately released vial.
Read the original sourceFDA review · benefit-risk and pooled safety
FDA regulatory review
US Food and Drug Administration, NDA 210797, 2019.
FDA reviewed three controlled EPP studies enrolling 244 adults. The review reports serious adverse events in 4% of afamelanotide recipients and 3% of vehicle recipients, with implant-site reactions and hyperpigmentation among common adverse reactions, and supported approval only for the EPP indication.
- Participants / model
- Adults in the Scenesse EPP development program
- Treatment
- Controlled-release afamelanotide implant
- Study design
- FDA integrated benefit-risk review
Three-person PK study · oral exposure absent
Human crossover pharmacokinetic study
Ugwu SO et al. European Journal of Pharmaceutical Sciences, 1997.
Three healthy men received afamelanotide by several routes. The investigators detected exposure after intravenous and subcutaneous dosing but not after oral administration; the reported beta half-life was about 0.8 to 1.7 hours in this tiny study.
- Participants / model
- 3 healthy male volunteers
- Treatment
- Intravenous, subcutaneous, intramuscular, intranasal, and oral administration in crossover periods
- Study design
- Open crossover pharmacokinetic study
Three people cannot define efficacy or uncommon safety, and the free-peptide PK does not describe the controlled-release implant.
Read the original sourceSeven-person tanning study · local pigment measures
Small human experiment
Barnetson RS et al. British Journal of Dermatology, 2000.
Seven volunteers received ten subcutaneous injections at assigned skin sites. Increased tanning and eumelanin were measured at some active sites. The experiment was small, short, site-specific, and did not establish long-term cosmetic benefit or safety.
- Participants / model
- 7 healthy volunteers
- Treatment
- Ten local subcutaneous injections with site controls
- Follow-up
- Short experimental course
- Study design
- Within-person controlled pigment experiment
Why is Melanotan I (afamelanotide) in C tier?
C tier covers the broader compound page, including unapproved cosmetic use. The 16 mg controlled-release implant has FDA approval and randomized evidence for EPP, while vials, nasal products, free peptide, and cosmetic tanning remain outside that approval.