Afamelanotide

What it is

Melanotan I is the original research name for afamelanotide, [Nle4-D-Phe7]-alpha-MSH, a synthetic 13-amino-acid analogue of alpha-melanocyte-stimulating hormone originally tested in humans for skin tanning without UV exposure. As a 16 mg controlled-release implant sold as Scenesse, afamelanotide is an approved medicine in the European Union and, since 2019, in the United States for adults with erythropoietic protoporphyria. Research peptide material sold as Melanotan I is not that licensed product, and it is a different molecule from Melanotan II.

How it works

Afamelanotide is an agonist at the melanocortin-1 receptor on melanocytes, where it stimulates eumelanin synthesis without UV exposure. The added pigment is thought to reduce skin penetration of the light that triggers phototoxic pain in protoporphyria.

Regulatory status

1. Cosmetic ingredient
2. Research compound
3. In clinical trials
4. Approved medicine

Approved as a medicine by the FDA or the EMA for at least one indication. Approval covers the named indication and formulation only.

What published research is studying

• Pain-free sunlight exposure in erythropoietic protoporphyria (two Phase 3 trials and post-authorisation cohorts)
• Skin darkening and eumelanin content in healthy volunteers
• Reduction of UV-induced sunburn cells and DNA damage in fair-skinned adults
• Repigmentation combined with narrowband UV-B phototherapy in vitiligo

Key findings

1. 01

   In two randomised double-blind Phase 3 trials in erythropoietic protoporphyria, median pain-free time in direct sunlight was 69.4 versus 40.8 hours with placebo after 6 months in 94 U.S. patients, and 6.0 versus 0.8 hours after 9 months in 74 European patients.

   Langendonk JG et al., N Engl J Med 2015
2. 02

   In a post-authorisation cohort of 117 patients with erythropoietic protoporphyria at a Dutch centre, followed for a median 2.0 years, time spent outside rose by 6.1 hours per week and disease-specific quality of life by 14%, while the number of phototoxic reactions did not change significantly.

   Wensink D et al., JAMA Dermatol 2020
3. 03

   In a randomised placebo-controlled trial in 65 fair-skinned volunteers given three 10-day courses over 3 months, melanin density rose 41% in those with low minimal erythemal dose, in whom UV-induced sunburn cells fell by more than 50%, and basal-layer thymine dimers fell 59%.

   Barnetson RS et al., J Invest Dermatol 2006
4. 04

   In a randomised double-blind trial in 28 healthy white men given 10 subcutaneous injections over 12 days, skin darkened significantly in both poor-tanning and good-tanning skin types, with no darkening on placebo and a peak 1 to 3 weeks after dosing ended.

   Levine N et al., JAMA 1991
5. 05

   In a randomised multicentre trial in 55 adults with nonsegmental vitiligo, afamelanotide implants plus narrowband UV-B reached 48.6% repigmentation at day 168 versus 33.3% with narrowband UV-B alone.

   Lim HW et al., JAMA Dermatol 2015

How strong is the evidence?

Common questions