Study summary · research use only
Advances in the management of erythropoietic protoporphyria - role of afamelanotide
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review article (species: human) discusses management of erythropoietic protoporphyria (EPP) and the phenotypically similar X-linked protoporphyria (XLPP), inherited disorders involving overproduction of protoporphyrin (PP) linked to a ferrochelatase gene defect in EPP and, in XLPP, typically a four-base deletion mutation in the gene encoding 5-aminolevulinic acid synthase-2. The excess PP is described as causing photosensitivity activated by light in the 380-420 nm range. The review discusses afamelanotide (Scenesse), a synthetic analog of α-melanocyte stimulating hormone reported to increase melanin production and sunlight tolerance in people with EPP/XLPP, notes it is approved in the European Union and Switzerland and was under US FDA review at the time of writing, and summarizes results from several Phase II and Phase III clinical trials without citing specific numeric outcomes here.
Abstract
Erythropoietic protoporphyria (EPP) and the phenotypically similar disease X-linked protoporphyria (XLPP) are inherited cutaneous porphyrias characterized clinically by acute non-blistering photosensitivity, intolerance to sunlight, and significantly reduced quality of life. They are due to marked overproduction of protoporphyrin (PP) chiefly by erythroblasts and reticulocytes. In EPP, the underlying genetic defect is in the ferrochelatase gene, which encodes the final enzyme in the heme synthetic pathway. In XLPP, the genetic defect is a gain-of-function mutation, usually a four-base deletion, in the gene that encodes the enzyme 5-aminolevulinic acid synthase-2, the first and rate-controlling enzyme of heme synthesis in developing red blood cells. The excess PP causes acute and painful photosensitivity, being activated by light in the long ultraviolet to blue spectrum (380-420 nm, the Soret band). Although several treatments have been proposed, presently no very effective treatment exists for EPP or XLPP. Afamelanotide (Scenesse®) is a first-in-class synthetic analog of α-melanocyte stimulating hormone. Afamelanotide mimics the naturally occurring hormone to increase skin pigmentation by increasing melanin production in melanocytes, resulting in increased sunlight tolerance in those with EPP/XLPP. Afamelanotide is currently approved for use in the European Union and Switzerland, and it is under review in the United States by the Food and Drug Administration for use in patients with EPP/XLPP. This paper provides a review of the clinical characteristics and current therapies for EPP/XLPP. We discuss the pharmacology, clinical efficacy, safety, and tolerability of afamelanotide and summarize the results of several key Phase II and III clinical trials. These data indicate that afamelanotide is a promising therapy for those with these debilitating diseases.
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