Hereditary angioedema patients would prefer newer-generation oral prophylaxis

Geba, Daniela; Sani, Johan Mohd; Gascon, Michaela; Hahn, Rebecca; Aggarwal, Kamal; Rosselli, Jinky

doi:10.1080/21556660.2020.1863699

Cited by 18 publications

(20 citation statements)

References 29 publications

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“…Therefore, most patients have high expectations toward new oral prophylactic medication. 41 In addition, previous studies reported that HAE therapies have been associated with unintended pharmacologic event including thrombosis, anaphylaxis, liver adenomas, and emboli. 42,43 For this reason, certain drugs are not recommended for pregnant women or patients with porphyria, cancer, or heart disease.…”

Section: Discussionmentioning

confidence: 99%

“…Although all currently marketed drugs show efficacy in controlling symptoms, most require IV or subcutaneous injection for administration, which is not only inconvenient to patients but also causes side effects including bleeding, rash, infection, inflammation, and itching at the injection site. Therefore, most patients have high expectations toward new oral prophylactic medication 41 . In addition, previous studies reported that HAE therapies have been associated with unintended pharmacologic event including thrombosis, anaphylaxis, liver adenomas, and emboli 42,43 .…”

Section: Discussionmentioning

confidence: 99%

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CU06‐1004 alleviates vascular hyperpermeability in a murine model of hereditary angioedema by protecting the endothelium

Lee

Kim

et al. 2023

Allergy

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Background: Over-release of the vasoactive peptide bradykinin (BK) due to mutation in the SERPING1 gene is the leading cause of hereditary angioedema (HAE). BK directly activates endothelial cells and increases vascular permeability by disrupting the endothelial barrier, leading to angioedema affecting face, lips, extremities, gastrointestinal tract, and larynx. Although various pharmacological treatment options for HAE became available during the last decade, they are presently limited and pose a major economic burden on patients. To identify additional therapeutic options for HAE, we evaluated the effect of CU06-1004, an endothelial dysfunction blocker, on BK-induced vascular hyperpermeability and the HAE murine model. Methods:To investigate the effect of CU06-1004 on BK-induced vascular hyperpermeability in vivo, we pre-administrated WT mice with the drug and then induced vascular leakage through intravenous injection of BK and observed vascular alternation.Then, SERPING1 deficient mice were used for a HAE murine model. For an in vitro model, the HUVEC monolayer was pre-treated with CU06-1004 and then stimulated with BK.Results: Bradykinin disrupted the endothelial barrier and formed interendothelial cell gaps, leading to hyperpermeability in vivo and in vitro. However, CU06-1004 treatment protected the endothelial barrier by suppressing Src and myosin light chain activation via BK and alleviated hyperpermeability. Conclusion:Our study shows that CU06-1004 oral administration significantly reduced vascular hyperpermeability in the HAE murine model by protecting the endothelial barrier function against BK stimulation. Therefore, protecting endothelium against BK with CU06-1004 could serve as a potential prophylactic/therapeutic approach for HAE patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CU06‐1004 alleviates vascular hyperpermeability in a murine model of hereditary angioedema by protecting the endothelium

Lee

Kim

et al. 2023

Allergy

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“… 52 , 78 In a survey study of 75 patients with HAE-C1-INH, almost all users of prophylactic therapy indicated that, despite liking their current medication, they would prefer an oral option if available because they believed that this would be a better fit with their lifestyle versus an injectable treatment. 79 In this same study, 67% of users of prophylactic therapy (including both intravenous and subcutaneous therapies) agreed that avoiding needles was the primary reason they would try an oral prophylactic medicine.…”

Section: Treatment Of Hae-ni-c1-inhmentioning

confidence: 93%

Managing Diagnosis, Treatment, and Burden of Disease in Hereditary Angioedema Patients with Normal C1-Esterase Inhibitor

Jones¹,

Zafra²,

Anderson³

2023

JAA

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Hereditary angioedema (HAE) is a rare, chronic, and debilitating genetic disorder characterized by recurrent and unpredictable swelling episodes that primarily affect the subcutaneous and/or submucosal tissues of the extremities, larynx, face, abdomen, and genitals. Most cases of HAE are caused by mutations in the serpin family G member 1 gene ( SERPING1 ), which encodes C1-esterase inhibitor (C1-INH) protein. Mutations in SERPING1 lead to deficient (type I HAE-C1-INH) or dysfunctional (type II HAE-C1-INH) C1-INH protein and subsequent dysregulation of the kallikrein–bradykinin cascade. However, some patients present with a third type of HAE (HAE-nI-C1-INH), which was first described in the year 2000 and is characterized by an absence of mutations in SERPING1 . Although mutations in the coagulation factor XII, angiopoietin-1, plasminogen, kininogen-1, myoferlin, and heparan sulfate-glucosamine 3-O-sulfotransferase-6 genes have been identified in some patients with HAE-nI-C1-INH, genetic cause is still unknown in many cases, hindering full elucidation of the pathology of this HAE subtype. Diagnosis of HAE-nI-C1-INH is also further complicated by the fact that patients typically demonstrate normal plasma levels of C1-INH and complement component 4 protein and normal C1-INH functionality during laboratory analysis. Therefore, we review the challenges associated with diagnosing, treating, and living with HAE-nI-C1-INH. We conclude that raising awareness of the presenting features of HAE-nI-C1-INH within the clinical setting and among the general public is critical to aid earlier suspicion and diagnosis of the disease. Furthermore, adopting an individualized approach to HAE-nI-C1-INH treatment is essential to help address the current and significant unmet needs in this patient population.

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“…However, due to the need for commitment to more frequent office visits for medication administrations, monitoring for potential injection-site reactions, and other infusion-/injection-specific side effects, many studies have reported patients' preference for oral medications over medications delivered by other routes of administration. [1][2][3] Because different medication formulations are typically associated with competing benefits and risks, it is critical that patients, providers, and formulary decision makers have a clear path for assessing the value of new formulations.…”

Section: Introductionmentioning

confidence: 99%

Quantifying the Value of Introducing an Oral Drug Delivery Option for Edaravone: A Review of Analyses Evaluating the Economic Impact of Oral versus Intravenous Formulations

Ronquest¹,

Paret²,

Lucas³

et al. 2022

CEOR

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Background Drug formulation and route of administration can have an impact on not only patients’ quality of life and disease outcomes but also costs of care. It is essential for decision makers to use appropriate economic modeling methods to guide drug coverage policies and to support patients’ decision-making. Purpose To illustrate key cost considerations for decision makers in economic evaluation of innovative oral formulations as alternatives to intravenous medication. Materials and Methods A structured literature review was conducted using the PubMed database to examine methods used for quantifying the economic impact of introducing a new oral pharmaceutical formulation as an alternative to intravenous medication. To illustrate the methods described in this review, a cost-minimization analysis was conducted to quantify the impact of introducing an oral formulation of a medication originally developed as an intravenous treatment for amyotrophic lateral sclerosis. Results We identified 14 published evaluations of oral and intravenous formulations from 10 countries across a variety of disease areas. The identified studies used cost-effectiveness (n=10), cost-minimization (n=2), and cost-calculation (n=2) modeling approaches. All but one (13/14) reported outcomes from payers’ perspective, while societal perspectives were also incorporated in 3 of the reviewed evaluations. One study estimated costs from a public hospital’s perspective. Only a subset of the identified studies accounted for the effects of safety (n=6) or efficacy (n=8) differences on treatment costs when estimating the costs of a formulation choice. Many studies that omitted these aspects did not include rationales for their decisions. Conclusion We found significant design variations in published models that estimated the impact of an additional formulation option on the treatment costs to payers and the society. Models need to be accompanied with clear descriptions on rationales for their time horizons and assumptions on how different formulations may affect healthcare costs from the selected perspectives.

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Hereditary angioedema patients would prefer newer-generation oral prophylaxis

Cited by 18 publications

References 29 publications

CU06‐1004 alleviates vascular hyperpermeability in a murine model of hereditary angioedema by protecting the endothelium

CU06‐1004 alleviates vascular hyperpermeability in a murine model of hereditary angioedema by protecting the endothelium

Managing Diagnosis, Treatment, and Burden of Disease in Hereditary Angioedema Patients with Normal C1-Esterase Inhibitor

Quantifying the Value of Introducing an Oral Drug Delivery Option for Edaravone: A Review of Analyses Evaluating the Economic Impact of Oral versus Intravenous Formulations

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