Breakthrough Clinical Results
KalVista Pharmaceuticals announced positive data from the KONFIDENT-S trial at the EAACI Congress 2025, showcasing sebetralstat's efficacy as an oral, on-demand treatment for hereditary angioedema (HAE) attacks, even in patients already on long-term prophylaxis (LTP). The study demonstrated rapid symptom relief with sebetralstat, regardless of the type of LTP used. Real-world data also highlighted significant challenges with LTP adherence, emphasizing the need for effective on-demand options like sebetralstat. KalVista has filed multiple regulatory applications for sebetralstat's approval.
Key Highlights
- Sebetralstat demonstrated rapid and consistent relief for HAE breakthrough attacks in patients receiving various LTPs.
- Real-world data revealed significant challenges with LTP adherence, leading to increased on-demand treatment needs.
- Sebetralstat offers a potential solution as a fast-acting, easily administered oral treatment for HAE attacks.
- Multiple regulatory applications for sebetralstat have been filed globally.
Incidence and Prevalence
Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of swelling affecting various body parts, including the skin, gastrointestinal tract, and airways. While several sources mention a prevalence of approximately 1 in 10,000 to 1 in 50,000 individuals worldwide, more recent or precise global estimates are difficult to pinpoint from the provided PubMed abstracts.
Several studies focus on specific regions or countries, highlighting variations in prevalence and incidence. For instance, a 2009 nationwide survey in Japan suggested a lower prevalence than estimates from Europe and North America. A 2019 study in Mexico estimated a prevalence of 0.9 per 50,000 inhabitants. A 2016 meta-analysis of studies primarily from North America and Europe estimated the prevalence of HAE due to C1 inhibitor deficiency (C1-INH-HAE) to be between 1.1 and 1.6 per 100,000.
It's important to note that HAE encompasses different types, including Type I, Type II, and HAE with normal C1-INH. The prevalence of HAE with normal C1-INH is considered much lower than HAE types I and II. Additionally, diagnostic challenges and underdiagnosis can affect prevalence estimates.
While the provided abstracts don't offer a definitive, up-to-date global prevalence or incidence figure, they consistently emphasize the rarity of HAE and the need for increased awareness and improved diagnostic tools to better capture the true burden of this disease worldwide.
Economic Burden
Economic Burden of HAE in the USA:
- A 2019 study estimated the total economic burden of rare diseases in the US, including HAE, at $997 billion. This included $449 billion in direct medical costs, $437 billion in indirect costs, $73 billion in non-medical costs, and $38 billion in uncovered healthcare costs.
- A 2009 study estimated the annual per-patient cost of HAE at $42,000, with costs varying by attack severity: $14,000 for mild, $27,000 for moderate, and $96,000 for severe attacks. Hospital costs accounted for 67% of direct medical costs, and indirect costs (missed work, lost productivity) totaled $16,000 annually per patient.
- A 2021 physician survey estimated 1230-1331 HAE-nl-C1INH patients in the US. The mean time to diagnosis was approximately 6 years.
- A 2013 patient survey found that 72% of HAE-C1INH patients and 76% of HAE-nlC1INH patients reported a significant impact of HAE on their quality of life. Most patients had access to on-demand treatment, but fewer HAE-nlC1INH patients (50%) had individual treatment plans compared to HAE-C1INH patients (76%).
- A 2017 patient survey found that most patients (78.7%) experienced an attack within the past month. The most common symptoms were abdominal and extremity swelling, pain, and abdominal and non-abdominal swelling. Most patients (68.5%) received long-term prophylaxis. Many patients reported anxiety (49.9%) and depression (24.0%). The mean impairment percentages were 5.9% for absenteeism, 23.0% for presenteeism, 25.4% for work productivity loss, and 31.8% for activity impairment.
- A 2018 patient survey found that over half (52%) of patients on prophylactic treatment found it burdensome. 98% of these patients would prefer an oral treatment if available, primarily due to convenience.
- A 2022 patient survey found that 86% of respondents delayed on-demand treatment, despite recognizing the onset of an attack. Reasons for delay included attack severity, cost, anxiety about refills, pain associated with treatment, lack of privacy for administration, lack of time to prepare treatment, and fear of needles.
Economic Burden of HAE in Europe:
- A 2014 study (HAE-BOIS-Europe) found that 59% of patients had at least one attack per month, 67% reported moderate-to-severe pain during their last attack, and 74% reported moderate-to-severe swelling. The most common attack sites were the abdomen and extremities. HAE significantly impacted daily activities both during and between attacks. Patients reported substantial anxiety about future attacks, traveling, and passing HAE to their children. 38% had clinically meaningful anxiety and 14% had clinically meaningful depression.
- A 2020 study (HDBOI) estimated the annual costs of Huntington's disease (which shares some similarities with HAE in terms of genetic basis and impact on quality of life) in five European countries and the USA. The average annual direct medical cost was €12,663, non-medical cost was €2984, and indirect cost was €47,576. Costs increased with disease stage.
- A 2018 study found that the annual per-patient direct medical cost of Crohn's disease (another chronic condition) was approximately €3500 and ulcerative colitis was approximately €2000, with substantial indirect costs from work productivity loss (€1900 per patient yearly).
It is important to note that the economic burden of HAE can vary significantly depending on disease severity, access to treatment, and healthcare system factors. More recent studies with larger sample sizes and standardized methodologies are needed to provide more precise and up-to-date estimates of the economic burden of HAE in both the USA and Europe.
Drug used in other indications
The provided text focuses on Sebetralstat for the on-demand treatment of Hereditary Angioedema (HAE) attacks. It highlights its benefits as an oral plasma kallikrein inhibitor, offering a convenient alternative to injections. The text does not mention Sebetralstat being trialled for any other indications besides HAE.