2026-03-26 | New and currently investigated pharmacotherapies for the erythropoietic protoporphyrias: spotlight on dersimelagon and bitopertin.
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. 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. 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.
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2026-03-12 | Hematopoietic stem cell transplantation for erythropoietic porphyria-induced acute liver failure: a case report and literature review.
Protoporphyrias are rare genetic disorders in heme biosynthesis, causing protoporphyrin IX accumulation with progressive liver injury. Liver transplantation has traditionally treated protoporphyria-induced liver injury but does not correct the underlying hematopoietic defect. We present a 16-year-old male with painful cutaneous photosensitivity who developed cholestatic liver dysfunction and severe abdominal pain. After plasmapheresis, red blood cell (RBC) transfusions, and intravenous hemin, he had transient improvement and subsequently underwent hematopoietic stem cell transplantation (HSCT) without liver transplantation, which normalized his protoporphyrin levels, liver function, and symptoms. This case underscores HSCT as a disease-modifying therapy that may prevent liver transplantation when performed before irreversible hepatic damage.
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2025-12-31 | Congenital Erythropoietic Porphyria with Persistent Severe Biochemical Abnormalities and a Non-Mutilating Clinical Course: A Case Report
Congenital erythropoietic porphyria (CEP), also known as Günther disease, is a rare autosomal recessive porphyria caused by deficiency of uroporphyrinogen III synthase, leading to accumulation of phototoxic type I porphyrins. CEP classically presents in infancy with severe photosensitivity, blistering, scarring, and hemolytic anemia; however, significant phenotypic variability has increasingly been recognized. We report 32-year-old women diagnosed with CEP in early infancy who demonstrated persistently and profoundly elevated erythrocyte porphyrin levels over more than a decade yet followed a relatively non-mutilating clinical course. Genetic testing identified a low penetrance intronic UROS variant typically associated with erythropoietic protoporphyria, underscoring diagnostic challenges and genotype-phenotype discordance. The patient experienced marked improvement in photosensitivity and burning pain after initiation of afamelanotide, without need for transfusion therapy or stem cell transplantation. This case highlights the heterogeneity of CEP, the importance of long-term biochemical follow up, and the potential role of afamelanotide in improving quality of life for selected patients with CEP.
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