Clinuvel Pharmaceuticals Limited announced the first positive results from a study evaluating the protective effects of afamelanotide on skin exposed to ultraviolet (UV) radiation (CUV151). The study, conducted at Salford Royal Hospital, Manchester, showed that systemic treatment with afamelanotide decreased the UV-erythema dose-response following ultraviolet radiation (UVR), indicative of reducing the first signs of UV-induced DNA damage. Analyses of biopsies that were taken during the study, assessing the drug's influence on DNA repair capacity, are pending.

Study design CUV151: The objective of the study was to assess the impact of afamelanotide on UV-induced DNA-damage and repair capacity in healthy volunteers with fair skin types (Fitzpatrick I-III)¹ by measuring: changes in UVR erythema dose response following treatment with afamelanotide; changes in minimal erythema dose (MED) following treatment with afamelanotide - an increased MED indicates a greater resistance to the mutagenic effects of UVR; the amount of DNA damage, and DNA damage repair following exposure to controlled doses of UVR. Manchester University is a renowned specialist centre which undertakes advanced clinical research in skin cancer, and its affiliate hospital (Salford Royal) was chosen for the study. Nine healthy adult volunteers were administered UVR by a solar simulator under controlled clinical conditions.

Evaluation of the skin occurred before and after UVR. Results CUV151: From a safety perspective, afamelanotide was well tolerated with two patients reporting mild headache and one patient experiencing mild nausea. It was found that following UV irradiation, the UV-erythema (‘provoked sunburn damage') dose response was reduced (p=0.018).

The observed decrease of the UV dose-response indicates the reduction of DNA damage incurred following afamelanotide treatment. Consistent with earlier studies, skin melanin density increased following treatment with SCENESSE® (p<0.05). Relevance of the results: Scientific research has long focused on the identification of principal skin cancer risk factors, among which are DNA damage defects incurred due to solar radiation.

Short exposure to UVR, and evidently a first sunburn, causes loss of DNA integrity through the formation of helical breaks, and the formation of single-strand dimers (cyclobutane pyrimidine dimers, CPDs), thereby increasing the risk of skin cancer(s). The scope of this study is limited to erythemal UVR and direct DNA damage. Following the use of solar-simulated UVR, reduction of UV dose-response, and increased melanisation shows the potential of systemically2 used afamelanotide to significantly reduce solar skin damage, erythema, and therefore first DNA lesions.

These results in healthy subjects confirm the earlier results of study CUV156 in xeroderma pigmentosum (XP) patients, who suffer from the highest risk of developing skin cancers due to a defect in DNA-repair mechanisms (‘Afamelanotide Reduces DNA Photodamage in Xeroderma Pigmentosum', 16 January 2023). The results in CUV156 showed a reduction in CPDs following dosing of afamelanotide. As seen in previous studies, in CUV151 it was confirmed that afamelanotide increases human skin pigmentation, which is strongly associated with photoprotection against systemic oxidative stress caused by solar radiation, and which may further reflect the drug's and melanin's antioxidative properties.