Afamelanotide in the Treatment of Dermatologic Disease

Morgan M. McNeil, DO; Amanda F. Nahhas, DO; Taylor L. Braunberger, MD; Iltefat H. Hamzavi, MD


Skin Therapy Letter. 2018;23(6) 

In This Article

Abstract and Introduction


Afamelanotide, an α-melanocyte stimulating hormone analogue, has become an emerging therapeutic option for a variety of skin conditions previously refractory to other treatments. Its efficacy has been demonstrated in several dermatologic conditions, including erythropoietic protoporphyria (EPP), solar urticaria, polymorphic light eruption (PMLE), vitiligo, acne, and Hailey-Hailey disease. Its relatively low risk side effect profile makes it an attractive treatment option and also paves the way for innovative use in other disorders.


Afamelanotide (Scenesse®) is a subcutaneous, controlledrelease, injectable α-melanocyte stimulating hormone (α-MSH) analogue.[1] Afamelanotide is composed of a linear peptide of thirteen amino acids, two of which differ from α-MSH. These two different amino acids increase the affinity of afamelanotide to the melanocortin 1 receptor (MC1R), which in turn increase the stability, potency, and half-life of afamelanotide.[1] Afamelanotide, like α-MSH, binds to MC1R in dermal cells and in melanocytes, thereby stimulating melanocyte production of eumelanin as well as melanocyte proliferation.[1] Eumelanin exhibits numerous roles, including photoprotection against ultraviolet (UV) light and scavenging of free radicals, while also filtering out longer wavelengths of visible light.[1] Therefore, afamelanotide is photoprotective against visible light photosensitivity and, thus, it is an effective treatment option for disorders such as erythropoietic protoporphyria (EPP), solar urticaria, and polymorphic light eruption (PMLE). Melanin also has antioxidant effects that help protect the skin against free radicals. Since such oxidative stress is responsible for inducing the painful symptoms experienced by patients with EPP and certain other dermatologic disorders in which oxygen free radicals are created upon visible light exposure, melanin replacement can help alleviate the associated discomfort.[1]

Pharmacokinetics studies reveal that subcutaneous delivery of afamelanotide results in full bioavailability, whereas oral and transdermal routes of administration inhibit measurable plasma concentrations or a pigmentation response, thus establishing its development as a subcutaneous injectable implant.[1] Although not recommended by the manufacturer for use as a sunscreen, afamelanotide has been shown to enhance DNA repair processes following UV damage in keratinocytes through MC1R signaling.[1,2] The side effect profile is reported to be minimal and includes nausea, headache and pigmentation, the latter of which could be seen as either a desirable endpoint in conditions such as vitiligo if inducing new pigment formation in previously depigmented macules or patches, or as an adverse event if new pigment appears hyperpigmented relative to a patient's baseline skin hue.[1] Afamelanotide was first approved for the treatment of EPP in Europe and is currently under study in both the United States and Europe for its use in other dermatologic disorders.[3] We present a discussion of the various conditions that have been treated by afamelanotide and the rationale supporting its use in each condition.