Clinuvel Pharmarceuticals has obtained a positive outcome with the second set of results from a study (CUV151) evaluating the DNA repair capacity of afamelanotide on skin exposed to ultraviolet (UV) radiation.
The study was conducted at Salford Royal Hospital, Manchester, a leading centre in assessing the effects of UV- induced skin damage.
The CUV151 study enrolled 10healthy volunteers with fair skin type, nine of whom received afamelanotide treatment and were included in the analyses. The volunteers were administered SCENESSE and exposed to controlled UV irradiation, both before and after treatment.
Biopsies of irradiated skin showed that DNA photodamage, expressed as bulky DNA adducts (cyclobutane pyrimidine dimers or CPDs), was significantly reduced at several time points following afamelanotide treatment, compared to baseline. Following afamelanotide, the percentage of cells presenting CPDs was reduced significantly at 15 minutes, 24 hours, and 48 hours following UV irradiation.
These results complement those obtained in February, when it was found that damage – characterised by the UV-erythema (“provoked sunburn damage”) dose response – had been reduced,Consistent with earlier studies, melanin density (skin pigmentation) significantly increased following treatment with SCENESSE.
These results will be presented at the European Association of Dermatology and Venereology in Berlin in October 2023. A further set of skin biopsy analyses assessing DNA markers are to follow.
Following the use of controlled UV radiation, a demonstrated reduction of CPDs indicates the potential of systemically administered afamelanotide to significantly reduce DNA skin damage caused by solar radiation and, ultimately, skin cancer. The results also show – for the first time – that afamelanotide treatment results in a significant reduction in DNA damage both shortly after irradiation (15 minutes) and over a subsequently longer time point (48 hours). Results from CUV151 released earlier this year found that individuals who received afamelanotide showed a reduced UV dose-response, and increased melanisation. Both sets of results from CUV151 strongly point to the photoprotective reparative afamelanotide.
The CUV151 analyses from 100 healthy subjects also confirm the results of study CUV156 in xeroderma pigmentosum (XP) patients, who suffer from the 40 highest risk of developing skin cancers due to a defect in DNA repair mechanisms.
The biopsies in three XP patients (CUV156) showed a significant reduction in CPDs following afamelanotide administration.
“These results add to a momentum, when all the pieces of the puzzle and data come together from our DNA Repair Program,” Clinuvel’s Head of Clinical Operations, Dr Pilar Bilbao said. “It is widely accepted that decreasing DNA photoproducts leads to a reduced risk and development of skin cancers, and we are working to evaluate these effects in high-risk populations.
“We are the first company to run a comprehensive programme using a human hormone analogue to show its effects on lessening DNA photodamage caused by UV, both in fair skinned individuals and XP patients, who are at highest risk of developing skin cancers following UV irradiation. It is very exciting for our team to further this programme with more patients, and more centres now prepared to join.
These data not only support our clinical work to pursue a marketing authorisation for the use of afamelanotide in XP patients – who are at high risk of developing multiple skin cancers per year and are left to lead an isolated life – but also for our photocosmetic product lines,” Dr Bilbao said.