Clinuvel Pharmaceuticals has reported data from a Phase II CUV156 study of its melanocortin drug, afamelanotide, in xeroderma pigmentosum (XP) patients.
The study was designed for assessing afamelanotide’s safety in XPC patients. It also evaluated the drug’s ability to help reparative processes after ultraviolet (UV) light-provoked DNA damage of the skin.
It was conducted over ten weeks, with a follow up after six months.
In the trial, the participants were given six afamelanotide doses along with controlled UVB radiation on unexposed areas of the skin (buttocks), with assessments of DNA markers.
The company stated that UVB helps in assessing the tolerance (MED) to the point of inducing DNA skin lesions, cyclobutane pyrimidine dimers (CPDs), characteristic for photodamage.
Before and after treatment, the participants’ skin biopsies were taken from UVB irradiated and non-irradiated anatomical sites.
The biopsies were analysed through immunohistochemical staining (IHC; microscopic analyses).
The findings from the three XP participants treated with afamelanotide showed a reduction in CPDs, most specifically in the deeper layer of the skin (basal layer of epidermis), as well as an increase in γH2AX, a DNA marker.
The skin specimens of two patients demonstrated an increase in p53 expression, which indicated the activation of the natural defence mechanisms.
Clinuvel Pharmaceuticals expert genomic scientist Dr Jessica Nucci said: “With great enthusiasm, and most of all to the satisfaction of XPC patients, we have learned for the first time that afamelanotide provides assisted DNA repair by reducing photoproducts and decreasing the risk factors of skin cancer development.
“Although a small sample for now, in many ways this is an immense clinical step forward in systemic photoprotection and addressing photodamage of the skin.
“We are all very much looking forward to the data from other XP patients to speed up the extension of commercial use of this drug for untreated patients.”