Hereditary hemorrhagic telangiectasia: Research & Drug Discovery Data

Drug discovery

drugs

With orphan designations

Overview

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder caused by mutations in ENG, ACVRL1, or SMAD4 genes, leading to abnormal vasculature with telangiectases and arteriovenous malformations (AVMs). Clinical hallmarks include recurrent epistaxis (>90% of adults), mucocutaneous telangiectases, and visceral AVMs (lungs, brain, liver, GI tract). Complications range from chronic anemia to life-threatening strokes or hemorrhages. Diagnosis follows the Curaçao criteria. Management combines antiangiogenics (bevacizumab), antifibrinolytics (tranexamic acid), iron supplementation, and procedural interventions for acute bleeding [1][3][7][16].

Population

Prevalence: ~1 in 5,000–8,000 individuals, though underdiagnosed; higher rates in Afro-Caribbean regions [2][7][12].
Median age of death is 3 years younger than general population, with 50% of patients developing GI bleeding by age 60 [2][4][14].

Burden

Morbidity: 30–50% develop pulmonary, cerebral, or hepatic AVMs; 32% with HHT require iron infusions [4][9][14].
Mortality: Hazard ratio 2.03 vs. controls, driven by stroke, cerebral abscess, and hemorrhage [14][18].
Costs: 40% higher healthcare utilization vs. matched controls, driven by frequent transfusions, imaging, and hospitalizations [9][19].

Therapies

Systemic therapies: Bevacizumab (reduces transfusion needs by >80%) and tranexamic acid (17–54% epistaxis reduction) [3][10][15].
Anemia management: IV iron for severe deficiency; transfusions reserved for hemodynamic instability [10][15].
Procedural: Argon Plasma Coagulation for acute GI bleeds; anticoagulation individualized based on bleeding risk [3][5][10].

Categories: rare circulatory system diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare hepatic diseases, rare neurological diseases, rare ophthalmic disorders, rare respiratory diseases, rare skin diseases, rare systemic and rheumatological diseases

Research Papers

1,129 drug discovery papers about Hereditary hemorrhagic telangiectasia, with 2 first-in-class and 27 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:

2026-07-07 | Expected survival is decreased in hereditary hemorrhagic telangiectasia: Results from a population-based registry study.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder associated with substantial morbidity. The aim of this study was to estimate mortality in a country without centralized national care for HHT patients. Moreover, we identified causes of death and estimated the prevalence of HHT in Sweden. The Swedish National Patient Register (NPR) was used to identify individuals with HHT using the International Classification of Diseases (ICD) code I78.0. Cases included all individuals with this code between January 1, 2001 and December 31, 2003 (n = 393). Five age- and gender-matched controls from the general population were selected by Statistics Sweden (SCB) (n = 1965). Cases and controls were followed for survival until 2018 using the Swedish National Cause of Death Register (DORS). To calculate prevalence, we identified all individuals with the ICD code I78.0 in the NPR over 12 years, from January 1, 2007 to December 30, 2018. Life expectancy for cases with HHT after age 30 was estimated at 73.0 (68.0-77.2) compared to 80.5 (79.1-82.0) years for controls. Ischemic heart diseases, diseases of arteries, arterioles, capillaries, and liver diseases were significantly more common causes of death among HHT patients. The prevalence of HHT was estimated at 9.3 per 100,000 over the 12 years. HHT in Sweden is associated with markedly shorter expected survival compared to the general population, and known complications of HHT are among the most common causes of death. The estimated prevalence of HHT in Sweden was relatively low, possibly due to underdiagnosis of those with milder symptoms.

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2026-06-30 | When Phenotype Outspeaks Genotype: Uncommon Vascular Anomalies in Suspected Hereditary Hemorrhagic Telangiectasia Despite Negative Genetic Testing.

Hereditary hemorrhagic telangiectasia (HHT) is an inherited vascular disorder characterized by abnormal blood vessel formation involving the skin and visceral organs. Establishing the diagnosis can be challenging, particularly in the absence of classic clinical manifestations or confirmatory genetic findings. We report the case of a 42-year-old woman who presented with acute epigastric pain and was found to have extensive vascular abnormalities involving the liver, lungs, aorta, and mesenteric circulation. She had no history of recurrent epistaxis, mucocutaneous telangiectasias, or family history of vascular disease, and genetic testing for known vascular disorders was negative. Despite the absence of typical clinical and genetic features, the distribution and extent of vascular involvement raised a strong suspicion for underlying HHT. This case highlights the potential for a broader phenotypic spectrum of HHT and underscores the limitations of current diagnostic criteria and genetic testing approaches.

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2026-06-29 | Atypical Presentation of Hereditary Hemorrhagic Telangiectasia Without Recurrent Epistaxis Leading to Delayed Diagnosis

Objective:Unusual clinical course Background:Hereditary hemorrhagic telangiectasia (HHT) is a rare vascular disorder characterized by multisystem arteriovenous malformations (AVMs).The earliest symptoms often appear in childhood and typically encompass recurrent epistaxis.Severe outcomes, including cerebral hemorrhage and thrombotic complications, can increase morbidity and mortality.HHT is estimated to have near-complete penetrance, such that 97% of patients exhibit symptoms by age 60. Case Report:A 71-year-old man presented with a 1-month history of progressive shortness of breath, fatigue, dizziness, and lower-extremity edema.Further evaluation revealed severe iron-deficiency anemia (hemoglobin 6.4 g/dL, serum iron 21 µg/dL, total iron-binding capacity 462 µg/dL, transferrin saturation ~ 5%, and ferritin 13 ng/mL).He received 4 units of packed red blood cells, resulting in symptomatic improvement.Imaging did not identify any additional visceral malformations; follow-up esophagogastroduodenoscopy and colonoscopy findings were normal.Despite negative endoscopic findings, intermittent occult gastrointestinal blood loss remained the leading consideration given his prior history of bleeding gastrointestinal AVMs and laboratory findings consistent with iron-deficiency anemia.Capsule endoscopy-recommended to screen for small-bowel telangiectasias-was deferred.His medical history was notable for a delayed diagnosis of HHT.He remained clinically asymptomatic until age 67, when he developed spontaneous bilateral subdural hematomas and gastrointestinal bleeding. Conclusions:This case highlights delayed recognition of HHT in the absence of recurrent epistaxis, followed by serious intracranial and gastrointestinal complications.Overreliance on classic mucocutaneous features may contribute to diagnostic delay.Clinicians should consider HHT in older adults with otherwise unexplained AVM-related hemorrhage or anemia to facilitate timely screening and management.

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2026-07-07 | Expected survival is decreased in hereditary hemorrhagic telangiectasia: Results from a population-based registry study.

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2026-06-30 | When Phenotype Outspeaks Genotype: Uncommon Vascular Anomalies in Suspected Hereditary Hemorrhagic Telangiectasia Despite Negative Genetic Testing.

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2026-06-29 | Atypical Presentation of Hereditary Hemorrhagic Telangiectasia Without Recurrent Epistaxis Leading to Delayed Diagnosis

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Drug Discovery Landscape

14 orphan drug designations for Hereditary hemorrhagic telangiectasia.

Drug	Therapy type	Regulator	Orphan designation	Approval	Sponsor
Human bispecific monoclonal antibody targeting ALK1 and BMPRII	antibodies	EMA	2025-07-18	—	Maxia Strategies-Europe Limited
BMPRII: ALK1 bispecific clustering agonist antibody	antibodies	FDA	2025-06-09	—	Diagonal Therapeutics
6-(4-(1-amino-3-hydroxycyclobutyl)phenyl)-1-ethyl-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one, L-tartrate salt	small molecules	EMA	2023-03-20	—	FGK Representative Service GmbH
6-(4-((1s,3s)-1-amino-3-hydroxycyclobutyl) phenyl)-1-ethyl-7- phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one L-Tartrate salt	small molecules	FDA	2022-12-07	—	Vaderis Therapeutics AG
Bevacizumab	antibodies	FDA	2022-10-12	—	Laboratoires Delbert SAS
pazopanib	small molecules	FDA	2019-10-09	—	HHT Foundation International (d/b/a Cure HHT)
Etamsylate	small molecules	EMA	2018-11-19	—	Dobecure S.L.
thalidomide	small molecules	FDA	2017-07-19	—	PlumeStars s.r.l.
Thalidomide	small molecules	EMA	2017-02-27	—	PlumeStars s.r.l.
Bevacizumab	antibodies	EMA	2014-12-16	—	Laboratoires Delbert
Bazedoxifene acetate	small molecules	EMA	2014-11-19	—	Consejo Superior de Investigaciones Cientificas (CSIC)
bevacizumab	antibodies	FDA	2010-10-21	—	Terence M. Davidson, MD
raloxifene hydrochloride	small molecules	FDA	2010-08-20	—	Consejo Superior de Investigaciones Cientificas
Raloxifene hydrochloride	small molecules	EMA	2010-06-10	—	Consejo Superior de Investigaciones Cientificas (CSIC)

Hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia

Overview

Population

Burden

Therapies

Categories: rare circulatory system diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare hepatic diseases, rare neurological diseases, rare ophthalmic disorders, rare respiratory diseases, rare skin diseases, rare systemic and rheumatological diseases

Research Papers

2026-07-07 | Expected survival is decreased in hereditary hemorrhagic telangiectasia: Results from a population-based registry study.

2026-06-30 | When Phenotype Outspeaks Genotype: Uncommon Vascular Anomalies in Suspected Hereditary Hemorrhagic Telangiectasia Despite Negative Genetic Testing.

2026-06-29 | Atypical Presentation of Hereditary Hemorrhagic Telangiectasia Without Recurrent Epistaxis Leading to Delayed Diagnosis

2026-07-07 | Expected survival is decreased in hereditary hemorrhagic telangiectasia: Results from a population-based registry study.

2026-06-30 | When Phenotype Outspeaks Genotype: Uncommon Vascular Anomalies in Suspected Hereditary Hemorrhagic Telangiectasia Despite Negative Genetic Testing.

2026-06-29 | Atypical Presentation of Hereditary Hemorrhagic Telangiectasia Without Recurrent Epistaxis Leading to Delayed Diagnosis

Drug Discovery Landscape

Updated: Aug 23, 2026