Breakthrough Clinical Results
KalVista Pharmaceuticals announced that the FDA will not meet the June 17, 2025 PDUFA goal date for sebetralstat, an investigational oral on-demand treatment for hereditary angioedema (HAE). The delay is attributed to the FDA's heavy workload and limited resources. The FDA has not raised concerns about sebetralstat's safety or efficacy, and expects a decision within four weeks. KalVista remains confident in the near-term approval of sebetralstat, which has the potential to become a foundational therapy for HAE management.
Key Highlights
- FDA will not meet the June 17, 2025 PDUFA goal date for sebetralstat due to resource constraints.
- The FDA has not raised safety or efficacy concerns regarding sebetralstat.
- The FDA expects to deliver a decision within approximately four weeks.
- Sebetralstat is a potential first oral, on-demand treatment for HAE.
Incidence and Prevalence
Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of swelling in various parts of the body. Several studies provide insights into the incidence and prevalence of this condition.
A 2023 systematic review examining the global burden of HAE found an overall prevalence between 0.13 and 1.6 cases per 100,000 individuals. This review encompassed all types of HAE, including Type 1, Type 2, and HAE with normal C1-INH. The study also highlighted the diagnostic challenges associated with HAE, with a mean or median delay in diagnosis ranging from 3.9 to 26 years after the initial onset of symptoms.
Another study, focusing specifically on HAE with normal C1-INH (HAE-nl-C1INH) in the United States, estimated a prevalence of 1,230 to 1,331 cases within the country between May 2019 and April 2020. This study also reported a mean diagnostic delay of approximately 6 years (range 2.4-13.5 years). It's important to note that HAE-nl-C1INH is considered less common than HAE types associated with C1-INH deficiency.
An earlier publication from 2018 stated that the prevalence of HAE with C1 inhibitor (C1-INH) deficiency varies widely, ranging from 1:50,000 to 1:100,000. The prevalence of HAE with normal C1-INH was described as unknown but likely much lower. This source also emphasized the significant disease burden associated with HAE, including unpredictable attacks, emotional impairment, reduced quality of life, and potential career impacts.
In summary, the prevalence of all HAE types combined is estimated to be between 0.13 and 1.6 per 100,000 globally. For HAE with C1-INH deficiency, the prevalence ranges from 1 in 50,000 to 1 in 100,000. HAE with normal C1-INH is less common, with a US-specific estimate of roughly 1,200-1,300 cases. It's crucial to recognize that these are estimates, and the true prevalence may vary due to diagnostic challenges and underreporting.
Economic Burden
Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of swelling. Several studies from PubMed provide insights into the economic burden of HAE in the USA and Europe.
USA:
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A 2010 study estimated the annual per-patient cost at $42,000, ranging from $14,000 for mild cases to $96,000 for severe attacks. Hospital costs accounted for 67% of direct medical costs, and indirect costs due to missed work and lost productivity totaled $16,000 annually for the average patient. A 2021 study reiterated these findings, emphasizing the substantial direct and indirect costs, particularly for severe cases. A 2011 study highlighted the potential for disease-specific treatments to improve quality of life and reduce costs associated with hospitalizations.
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A 2017 study reviewed the economic burden of rare diseases in the US, including 379 rare diseases. The total economic burden was estimated at $997 billion, with direct medical costs accounting for $449 billion (45%), indirect costs $437 billion (44%), non-medical costs $73 billion (7%), and uncovered healthcare costs $38 billion (4%). While this study doesn't isolate HAE, it underscores the significant economic impact of rare diseases in general.
Europe:
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A 2014 study aimed to assess the real-world experience of HAE in Europe through patient surveys and interviews. The study highlighted the significant impact of HAE on quality of life, including unnecessary treatments and procedures, symptom triggers, attack impacts, caregiver impacts, and long-term impacts like reduced work/school productivity and limited career advancement. While this study didn't provide specific cost estimates, it emphasized the substantial burden on patients and their families.
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A 2014 study focused on the humanistic and economic burden of HAE in Europe. The study collected data on healthcare resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning. While specific cost estimates were not provided in the abstract, the study aimed to characterize the burden from the patient perspective.
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A 2014 study assessed the direct and indirect resource utilization associated with HAE in Spain, Germany, and Denmark. The study found that attack severity was the most significant predictor of medical resource utilization. Among patients seeking medical care during an attack, over half used the emergency department. The last attack caused patients to miss an average of 4-12 hours of normal activities. Among working or studying patients, an estimated average of 20 days were missed from work/school per year due to HAE, and 51% reported that HAE hindered their career/educational advancement.
Overall:
The economic burden of HAE is substantial in both the USA and Europe, encompassing direct medical costs, indirect costs from lost productivity, and intangible costs related to reduced quality of life. While precise cost estimates vary across studies and regions, the available evidence consistently points to the significant economic impact of HAE on patients, families, healthcare systems, and society.
Sebetralstat is primarily known for its use in treating Hereditary Angioedema (HAE). The provided text focuses heavily on this application, discussing its efficacy, safety, and pharmacokinetic properties in the context of HAE. There is no mention of sebetralstat being trialed for any other indications besides HAE.