Scientific Beyond pigmentation: signs of liver protection during afamelanotide treatment in Swiss patients with erythropoietic protoporphyria, an observational s


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Beyond pigmentation: signs of liver protection during afamelanotide treatment in Swiss patients with erythropoietic protoporphyria, an observational study

First Published December 21, 2021

Erythropoietic protoporphyria (EPP) is an ultra-rare inherited disorder with overproduction of protoporphyrin in maturating erythroblasts. This excess protoporphyrin leads to incapacitating phototoxic burns in sunlight exposed skin. Its biliary elimination causes cholestatic liver injury in 20% and terminal liver failure in 4% of EPP patients. Thereby, the risk of liver injury increases with increasing erythrocyte protoporphyrin concentrations. Afamelanotide, an α-melanocyte-stimulating hormone (MSH) analog inducing skin pigmentation, was shown to improve sunlight tolerance in EPP. Beyond this well-known effect on pigmentation, the MSHs have liver-protective effects and improve survival of maturating erythroblasts, effects described in animal or in vitro models to date only. We investigated whether afamelanotide treatment in EPP has effects on erythropoiesis, protoporphyrin concentrations, and liver injury by analyzing retrospectively our long-term safety data.
From the 47 Swiss EPP-patients treated at our center since 2006, we included those 38 patients in the current analysis who received at least one afamelanotide dose between 2016 and 2018 and underwent regular laboratory testing before and during the treatment. We compared the means of pretreatment measurements with those during the treatment.
Protoporphyrin concentrations dropped from 21.39 ± 11.12 (mean ± SD) before afamelanotide to 16.83 ± 8.24 µmol/L (p < .0001) during treatment. Aspartate aminotransferase decreased from 26.67 ± 13.16 to 22.9 ± 7.76 IU/L (p = .0146). For both entities, patients with higher values showed a more progressive decrease, indicating a risk reduction of EPP-related liver disease. The pre-existing hypochromia and broad mean red-cell distribution width were further augmented under afamelanotide. This was more likely due to an influence of afamelanotide on maturating erythroblasts than due to an exacerbated iron deficiency, as mean zinc-protoporphyrin decreased significantly and ferritin remained unchanged. No serious afamelanotide-related adverse events were observed for a total of 240 treatment years.
Our findings point to a protective effect of afamelanotide on erythroblast maturation and protoporphyrin-induced liver injury.

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@sharelooker great finding 🙏
There were already discussions in the main forum as to whether Clinuvel already had evidence of DNA repair from EPP patients. I think this study clearly points it out and Clinuvel might have even more data. I think that’s the reason they are so confident. Also the safety profile of Afa is just incredible.

„Noteworthy, none of the patients developed precancerous or malignant skin lesions…The 38 patients accumulated a total of 240 treatment years and a total of 254 observation years.“


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And nice to see the social media team putting this out on Twitter and FB and on Christmas Day too. Although the paper has been out since 21 Dec so a good thing CUV staff read this board to help stay up-to-date
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...likely result in a reduced production of excess PPIX and, therefore, supports the hypothesis of a causative treatment effect...

This should justify a much higher price for the implant. It's no more only a preventive/symptomatic treatment!

NICE, did you understand?
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