New and currently investigated pharmacotherapies for the erythropoietic protoporphyrias: spotlight on dersimelagon and bitopertin.
This narrative review examines the current and investigational pharmacological treatments for erythropoietic protoporphyrias (EPP), a group of ultra-rare inherited disorders of heme biosynthesis causing severe, painful phototoxic reactions triggered by visible light exposure. The authors searched PubMed and clinical trial databases to synthesize available evidence on two investigational agents—dersimelagon (a melanocortin-1 receptor agonist) and bitopertin (a glycine transport inhibitor)—alongside the only currently approved therapy, afamelanotide. The review notes that afamelanotide effectively reduces pain and extends tolerable sun exposure time but does not address the underlying disease mechanism and is approved only for adults, leaving pediatric patients without a treatment option. The authors report that available trial data for both dersimelagon and bitopertin suggest treatment effects versus placebo, though they emphasize that the safety and efficacy profiles of both agents require further characterization. A key limitation highlighted is the absence of head-to-head comparison data against afamelanotide, which the authors argue is necessary to inform regulatory decisions and ensure meaningful patient access. The review concludes that both agents hold promise but that additional robust clinical evidence is needed before their roles in EPP management can be fully established.
Why this grade: This is a narrative review synthesizing existing trial data and literature rather than generating new primary clinical evidence, so it is graded as "review" rather than a direct human evidence tier.
Introduction The erythropoietic protoporphyrias (EPP) are ultra-rare inborn errors of the heme biosynthesis characterized by painful and debilitating phototoxic reactions in the blood vessels upon exposure to visible light. Afamelanotide is the only approved treatment for EPP and effectively prevents pain and prolongs the time patients can spend in sunlight. However, afamelanotide does not address the underlying disease mechanism and is currently only approved for use in adult patients, leaving children and adolescents without a treatment option. The two investigational pharmacotherapies, dersimelagon and bitopertin, could offer benefits such as treatment options for children and prevention of some of the associated disease complications. Areas covered This narrative review (using Pubmed and trial databases) aims to provide an overview of the status of development of dersimelagon and bitopertin, with a focus on the prevention of phototoxicity. Expert opinion The currently available trial data on dersimelagon and bitopertin suggests treatment effects in EPP as compared to placebo control groups. However, safety and efficacy of dersimelagon and bitopertin need to be further characterized. Moreover, to ensure benefit for patients and access to therapy after regulatory approval, it also would be important to generate data on the relative safety and efficacy as compared to afamelanotide.
Educational summary of published research — not medical advice. License: cc by-nc-nd. Full text is shown only where licensing permits.