PD03 Afamelanotide reduces the ultraviolet radiation erythemal response soon after application in healthy volunteers with skin phototypes II–III

Abstract Afamelanotide is a potent α-melanocyte stimulating hormone analogue that binds to the melanocortin 1 receptor and, over time, promotes tanning, conferring systemic photoprotection. Afamelanotide also has antioxidant properties and may promote repair of ultraviolet (UV) radiation (UVR)-induced DNA damage. The objectives of this study were to examine the short-term impact of afamelanotide on DNA damage repair mechanisms, UVR erythema and melanogenic responses in healthy human skin following exposure to UVR. Healthy men and women (n = 10) volunteers aged 27–43 years (median 34) of skin phototypes II–III were recruited. Reflectance spectrophotometry was performed on six body sites (photoexposed and photoprotected) to assess skin pigmentation, and then a geometric series of erythemally weighted doses (7–80 mJ cm−2) of broadband UVB (∼60% UVB, 40% UVA; Philips TL12) was applied to unexposed upper buttock skin. After 24 h, the minimal erythema dose (MED) was assessed and erythema intensity (CIE a*) was measured at each dose site. A subcutaneous implant of afamelanotide 16 mg was administered; 5 days later, the same UVR dose series was applied to unexposed contralateral upper buttock skin. After 24 h, the MED was assessed and repeat skin reflectance measurements were performed. The overall UVR–erythema dose response (area under curve) showed a significant decrease post-afamelanotide (mean 3.5 vs. 2.7; P = 0.018). There was an apparent increase in the median MED post-afamelanotide (24.5 vs. 29.9 mJ cm−2; not statistically significant). Reflectance measurements showed skin lightness (CIE L*) significantly decreased at only one site (central forehead, from 63.0 to 61.0; P = 0.015), while determination of melanin density by reflectance at 420 and 400 nm showed a statistically significant increase in density at all sites except the right abdomen, with a mean overall increase from 2.5% to 2.9% (P = 0.001). Our results indicate that afamelanotide reduces the overall UVR–erythema dose response in healthy human skin shortly after administration, with a small increase in melanogenesis, suggesting other nonmelanogenic properties of this agent contribute to the erythema protection. Further investigation will examine whether enhanced repair of UVR-induced DNA damage plays a role. Funding sources: research sponsored by CLINUVEL (UK) Ltd.