Clinuvel reports breakthrough against UV damage in skin DNA repair study using afamelanotide

Specialty pharmaceutical group Clinuvel Pharmaceuticals (ASX: CUV) has received promising outcomes from the final set of results from a study evaluating the DNA-repair capacity of its afamelanotide candidate.

For the general population, and specifically for individuals with fair skin types who sunburn easily, the results indicate that afamelanotide can reduce oxidative damage and inflammatory reactions after sun exposure and skin damage.

UV radiation exposure

The study on the skin of healthy volunteers exposed to ultraviolet (UV) radiation was conducted at Salford Royal Hospital in Manchester, with afamelanotide dosing found to lead to a reduction in differentially expressed genes (DEGs) in the skin.

“The results from RNA sequencing complement the earlier results we saw from immunohistochemistry, in that afamelanotide consistently seems to assist in the repair of UV-damaged DNA in the skin,” said chief scientific officer Dr Dennis Wright.

“The significance of these results evaluating the use of afamelanotide in reducing oxidative and inflammatory damage caused by UV is high for those at high risk of solar damage, sunburn and skin cancers, hence we will repeat and confirm these results in a final study.”

Fair skin types

The study analysed biopsies from seven patients with fair skin types taken prior to and six days after afamelanotide treatment.

Subsequent RNA sequencing found that without afamelanotide UV irradiation resulted in 625 DEGs in comparison to non-irradiated skin.

With afamelanotide, the DEGs between irradiated and non-irradiated skin reduced by a factor of 3.4 to 183.

The genes evaluated are crucial in the regulation of DNA repair and inflammatory reactions following solar and UV exposure.

The results illustrate that both skin damage – characterised by the UV erythema or provoked sunburn damage dose-response – and DNA damage markers had been significantly reduced.

European ODD grant

Afamelanotide received a positive opinion in late June for an orphan drug designation (ODD) from the European Medicines Agency (EMA) for the treatment of variegate porphyria (VP).

This designation is a step along the regulatory pathway to extend the existing approved label for SCENESSE (afamelanotide) to include VP, a genetic disorder that affects an estimated 1 in 300,000 individuals across Europe.

Assessing afamelanotide as a systemic photoprotective in VP, the EMA accepted a submission on its use as a systemic photoprotective.

The European ODD enables Clinuvel to receive regulatory support and commercial incentives throughout the development pathway, including post-authorisation market exclusivity of 10 years.

The company previously received approval from the US Food and Drug Administration in 2016 for the use of afamelanotide in VP.