RARE DISEASE
Porphyria
Porphyria
Porphyria
Drug discovery
10
drugs
With orphan designations
Overview
Porphyria encompasses rare genetic disorders disrupting heme synthesis, leading to neurovisceral or cutaneous manifestations. Acute hepatic porphyrias (e.g., AIP, VP, HCP) cause severe abdominal pain, autonomic instability, and neurological symptoms, triggered by medications, fasting, or hormonal changes [1][5][6]. Cutaneous forms (e.g., PCT, EPP) present with photosensitivity and blistering [1][5]. Diagnosis relies on elevated porphyrin precursors in urine/blood and genetic testing [6][13]. Treatments include heme infusion, givosiran, and trigger avoidance [3][6][18].
Burden
≥60% of patients experience chronic symptoms (pain, fatigue, neuropathy), with 29% requiring daily opioids [9][19].
High hospitalization rates, reduced quality of life, and increased hepatocellular carcinoma risk [4][9][14].
Economic impact from recurrent ER visits, missed workdays, and costly therapies [4][9][19].
Categories: rare genetic diseases, rare inborn errors of metabolism, rare renal diseases, rare skin diseases
Research Papers
1,241 drug discovery papers about Porphyria, with 3 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,241 drug discovery papers about Porphyria, with 3 first-in-class and 2 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-14 | Long-term cutaneous and systemic manifestatıons at the 70th anniversary of the porphyria turcica outbreak: a three-case series
This case series a re-evaluation of a historical patient cohort after 42 years provides valuable insights into the natural history of Porphyria Turcica. It has been confirmed that Case 1 is one of the individuals clinically documented in the landmark cohort study published by Cripps, Peters, and others in the *British Journal of Dermatology* in 1984
2026-08-08 | Challenges in Porphyria diagnosis and management: When variegate Porphyria meets HIV.
Variegate Porphyria (VP) is a rare autosomal dominant disorder characterized by deficient activity of protoporphyrinogen oxidase, resulting in the accumulation of potentially neurotoxic heme precursors. We present the case of a 32-year-old woman with HIV receiving antiretroviral therapy (dolutegravir, lamivudine, and ritonavir) who had generalized seizures, psychosis, and polyneuropathy, initially interpreted as secondary to infection. Brain magnetic resonance imaging suggested vasogenic edema, raising suspicion of autoimmune encephalitis. Despite treatment with methylprednisolone and intravenous immunoglobulins, her health worsened, requiring intensive care and extended mechanical ventilation. Markedly elevated urinary porphyrin precursors and porphyrins, a characteristic pattern of elevated fecal porphyrins, and a plasma fluorescence emission peak at 626 nm were diagnostic for VP. Genetic testing identified a pathogenic PPOX missense variant NM_001365398.1:c.428 A > T, p.(Asp143Val), consistent with VP. The patient required repeated courses of hemin and intravenous dextrose, which were followed by transient biochemical improvement. However, symptoms and biochemical markers recurred over time. Clinical stability was only achieved after the withdrawal of ritonavir from her antiretroviral regimen, emphasizing the need for careful medication review in patients with Acute Hepatic Porphyria. This case shows the complex interactions between genetic predisposition, environmental factors, and comorbidities in VP, emphasizing the importance of genetic and biochemical testing for accurate diagnosis, hemin administration during acute attacks, and careful medication review. Clinicians should remain vigilant about interactions between antiretroviral therapy and porphyria when treating HIV-positive patients with suspected or confirmed Acute Hepatic Porphyria.
2026-07-29 | From one-size-fits-all to on-demand: personalized crispr gene editing for rare genetic liver diseases.
Rare genetic liver diseases collectively affect millions of individuals worldwide and encompass a heterogeneous group of monogenic disorders including Wilson disease, alpha-1 antitrypsin deficiency, glycogen storage diseases, urea cycle disorders, progressive familial intrahepatic cholestasis, and acute hepatic porphyrias. While conventional management relies on dietary modification, pharmacotherapy, and ultimately liver transplantation, the advent of clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has opened transformative therapeutic avenues. This review provides a comprehensive and critical appraisal of the current landscape of CRISPR-based therapies for genetic liver diseases, from preclinical proof-of-concept studies to landmark clinical trials. We examine the evolution from conventional Cas9 nuclease-mediated editing to precision tools including base editors and prime editors, which enable single-nucleotide corrections without inducing double-strand DNA breaks. The role of lipid nanoparticle delivery systems in achieving efficient hepatocyte-targeted delivery is discussed, alongside emerging challenges in pediatric dosing and immunogenicity. We highlight the paradigm shift toward personalized, patient-specific CRISPR therapies, exemplified by the first-in-human bespoke gene editing treatment delivered in 2025. Competing nucleic acid technologies, including RNA interference and antisense oligonucleotides, are compared in terms of durability, safety, and cost-effectiveness. Finally, we critically evaluate the evolving regulatory landscape and propose a priority framework for selecting genetic liver diseases most amenable to CRISPR-based correction. This review underscores that CRISPR gene editing is transitioning from experimental promise to clinical reality for genetic liver diseases, with personalized approaches poised to redefine the treatment paradigm.
2026-07-28 | Case Report: HCV-triggered porphyria cutanea tarda in a patient with SEC23B-mutated congenital dyserythropoietic anemia type II.
Porphyria cutanea tarda (PCT) is a hepatic porphyria often triggered by hepatitis C virus (HCV) infection, iron overload, or environmental exposure. Congenital dyserythropoietic anemia type II (CDA II) caused by SEC23B mutations leads to ineffective erythropoiesis and secondary iron accumulation. We report a 34-year-old man with genetically confirmed SEC23B-mutated CDA II who developed photosensitive bullae associated with chronic HCV genotype 1b infection, hyperbilirubinemia, and severe iron overload. Urinary porphyrins were positive, and skin biopsy showed subepidermal bullae with PAS-positive deposits, supporting the diagnosis of PCT. After unsuccessful therapy with hydroxychloroquine, treatment with sofosbuvir/velpatasvir achieved sustained virologic response, resolution of skin lesions, and marked ferritin reduction. This case illustrates that viral and metabolic stressors can trigger PCT in CDA II patients with possible hepatic involvement, underscoring the importance of recognizing combined genetic and infectious factors in rare hematologic disorders.
2026-07-15 | Red lines and green lights: Gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.
Gene therapy is revolutionizing treatment paradigms for inherited haematological and immunological conditions. Recent successes, including the United States Food and Drug Administration (FDA) approval of gene therapy products for sickle cell disease and beta-thalassaemia, highlight the translational path of gene therapies for erythroid-specific disorders. In contrast, gene therapy development for other inherited erythroid disorders remains largely preclinical. Here, we examine the emerging landscape of gene therapies for inherited non-haemoglobinopathy erythroid disorders, focusing on the status of gene therapies for Diamond-Blackfan anaemia (DBA), pyruvate kinase deficiency (PKD), X-linked sideroblastic anaemia (XLSA), congenital erythropoietic porphyria (CEP) and congenital dyserythropoietic anaemia (CDA). We discuss the latest cellular engineering approaches being applied to developing therapies for these erythroid disorders and evolving strategies for conditioning and engraftment of modified cells. Despite the rarity of these disorders individually, several convergent biological and translational themes have emerged. Leveraging shared insights across diseases may accelerate clinical translation and broaden the curative potential of gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.
2026-08-14 | Long-term cutaneous and systemic manifestatıons at the 70th anniversary of the porphyria turcica outbreak: a three-case series
This case series a re-evaluation of a historical patient cohort after 42 years provides valuable insights into the natural history of Porphyria Turcica. It has been confirmed that Case 1 is one of the individuals clinically documented in the landmark cohort study published by Cripps, Peters, and others in the *British Journal of Dermatology* in 1984
2026-08-08 | Challenges in Porphyria diagnosis and management: When variegate Porphyria meets HIV.
Variegate Porphyria (VP) is a rare autosomal dominant disorder characterized by deficient activity of protoporphyrinogen oxidase, resulting in the accumulation of potentially neurotoxic heme precursors. We present the case of a 32-year-old woman with HIV receiving antiretroviral therapy (dolutegravir, lamivudine, and ritonavir) who had generalized seizures, psychosis, and polyneuropathy, initially interpreted as secondary to infection. Brain magnetic resonance imaging suggested vasogenic edema, raising suspicion of autoimmune encephalitis. Despite treatment with methylprednisolone and intravenous immunoglobulins, her health worsened, requiring intensive care and extended mechanical ventilation. Markedly elevated urinary porphyrin precursors and porphyrins, a characteristic pattern of elevated fecal porphyrins, and a plasma fluorescence emission peak at 626 nm were diagnostic for VP. Genetic testing identified a pathogenic PPOX missense variant NM_001365398.1:c.428 A > T, p.(Asp143Val), consistent with VP. The patient required repeated courses of hemin and intravenous dextrose, which were followed by transient biochemical improvement. However, symptoms and biochemical markers recurred over time. Clinical stability was only achieved after the withdrawal of ritonavir from her antiretroviral regimen, emphasizing the need for careful medication review in patients with Acute Hepatic Porphyria. This case shows the complex interactions between genetic predisposition, environmental factors, and comorbidities in VP, emphasizing the importance of genetic and biochemical testing for accurate diagnosis, hemin administration during acute attacks, and careful medication review. Clinicians should remain vigilant about interactions between antiretroviral therapy and porphyria when treating HIV-positive patients with suspected or confirmed Acute Hepatic Porphyria.
2026-07-29 | From one-size-fits-all to on-demand: personalized crispr gene editing for rare genetic liver diseases.
Rare genetic liver diseases collectively affect millions of individuals worldwide and encompass a heterogeneous group of monogenic disorders including Wilson disease, alpha-1 antitrypsin deficiency, glycogen storage diseases, urea cycle disorders, progressive familial intrahepatic cholestasis, and acute hepatic porphyrias. While conventional management relies on dietary modification, pharmacotherapy, and ultimately liver transplantation, the advent of clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has opened transformative therapeutic avenues. This review provides a comprehensive and critical appraisal of the current landscape of CRISPR-based therapies for genetic liver diseases, from preclinical proof-of-concept studies to landmark clinical trials. We examine the evolution from conventional Cas9 nuclease-mediated editing to precision tools including base editors and prime editors, which enable single-nucleotide corrections without inducing double-strand DNA breaks. The role of lipid nanoparticle delivery systems in achieving efficient hepatocyte-targeted delivery is discussed, alongside emerging challenges in pediatric dosing and immunogenicity. We highlight the paradigm shift toward personalized, patient-specific CRISPR therapies, exemplified by the first-in-human bespoke gene editing treatment delivered in 2025. Competing nucleic acid technologies, including RNA interference and antisense oligonucleotides, are compared in terms of durability, safety, and cost-effectiveness. Finally, we critically evaluate the evolving regulatory landscape and propose a priority framework for selecting genetic liver diseases most amenable to CRISPR-based correction. This review underscores that CRISPR gene editing is transitioning from experimental promise to clinical reality for genetic liver diseases, with personalized approaches poised to redefine the treatment paradigm.
2026-07-28 | Case Report: HCV-triggered porphyria cutanea tarda in a patient with SEC23B-mutated congenital dyserythropoietic anemia type II.
Porphyria cutanea tarda (PCT) is a hepatic porphyria often triggered by hepatitis C virus (HCV) infection, iron overload, or environmental exposure. Congenital dyserythropoietic anemia type II (CDA II) caused by SEC23B mutations leads to ineffective erythropoiesis and secondary iron accumulation. We report a 34-year-old man with genetically confirmed SEC23B-mutated CDA II who developed photosensitive bullae associated with chronic HCV genotype 1b infection, hyperbilirubinemia, and severe iron overload. Urinary porphyrins were positive, and skin biopsy showed subepidermal bullae with PAS-positive deposits, supporting the diagnosis of PCT. After unsuccessful therapy with hydroxychloroquine, treatment with sofosbuvir/velpatasvir achieved sustained virologic response, resolution of skin lesions, and marked ferritin reduction. This case illustrates that viral and metabolic stressors can trigger PCT in CDA II patients with possible hepatic involvement, underscoring the importance of recognizing combined genetic and infectious factors in rare hematologic disorders.
2026-07-15 | Red lines and green lights: Gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.
Gene therapy is revolutionizing treatment paradigms for inherited haematological and immunological conditions. Recent successes, including the United States Food and Drug Administration (FDA) approval of gene therapy products for sickle cell disease and beta-thalassaemia, highlight the translational path of gene therapies for erythroid-specific disorders. In contrast, gene therapy development for other inherited erythroid disorders remains largely preclinical. Here, we examine the emerging landscape of gene therapies for inherited non-haemoglobinopathy erythroid disorders, focusing on the status of gene therapies for Diamond-Blackfan anaemia (DBA), pyruvate kinase deficiency (PKD), X-linked sideroblastic anaemia (XLSA), congenital erythropoietic porphyria (CEP) and congenital dyserythropoietic anaemia (CDA). We discuss the latest cellular engineering approaches being applied to developing therapies for these erythroid disorders and evolving strategies for conditioning and engraftment of modified cells. Despite the rarity of these disorders individually, several convergent biological and translational themes have emerged. Leveraging shared insights across diseases may accelerate clinical translation and broaden the curative potential of gene therapy for inherited erythroid disorders beyond the haemoglobinopathies.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
10 orphan drug designations for Porphyria, including 2 approved therapies.
10 orphan drug designations for Porphyria, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Afamelanotide | peptides | EMA | 2024-07-25 | — | Clinuvel Europe Limited |
Dersimelagon | small molecules | EMA | 2022-03-16 | — | Tanabe Pharma GmbH |
(1-{2-[(3S,4R)-1-[(3R,4R)-1-cyclopentyl-3-fluoro-4-(4-methoxyphenyl) pyrrolidine-3-carbonyl]-4-(methoxymethyl)pyrrolidin-3-yl]-5-(trifluoromethyl)phenyl}piperidine-4-carboxylic acid-phosphoric acid (1/1)) | small molecules | FDA | 2020-06-08 | — | Tanabe Pharma America Inc. |
afamelanotide | peptides | FDA | 2016-02-04 | — | Clinuvel Inc. |
Adeno-associated viral vector serotype 5 containing the hydroxymethylbilane synthase gene | gene therapies | EMA | 2009-04-29 | — | uniQure Biopharma B.V |
afamelanotide [SCENESSE®] | peptides | FDA | 2008-07-17 | 2019-10-08 | Clinuvel Inc. |
RECOMBINANT HUMAN PORPHOBILINOGEN DEAMINASE [Porphozym (iv) / Porphogen (sc)] | proteins | EMA | 2002-06-12 | — | Chiesi Farmaceutici S.p.A. |
Hemin and zinc mesoporphyrin | small molecules | FDA | 1993-12-20 | — | Bonkovsky, Herbert L. M.D. |
Histrelin | small molecules | FDA | 1991-05-03 | — | Anderson, Karl E., M.D. |
Hemin [Panhematin] | proteins | FDA | 1984-03-16 | 1983-07-20 | Abbott Laboratories |
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