RARE DISEASE
Hereditary angioedema type 1
Hereditary angioedema type 1
Hereditary angioedema type 1
Synonyms: HAE 1, HAE-I, Hereditary angioneurotic edema type 1
Synonyms: HAE 1, HAE-I, Hereditary angioneurotic edema type 1
Synonyms: HAE 1, HAE-I, Hereditary angioneurotic edema type 1
Drug discovery
1
drug
With orphan designation
Overview
Hereditary angioedema type 1 (HAE-1) is an autosomal dominant disorder caused by SERPING1 gene mutations, resulting in deficiency of functional C1 esterase inhibitor (C1-INH). This leads to dysregulated bradykinin production, causing recurrent, unpredictable swelling attacks involving subcutaneous tissues, visceral organs, and upper airways (risk of asphyxiation) [1][2][15].
Burden
Clinical: 42% experience weekly attacks pre-diagnosis; 69% undergo unnecessary procedures due to delayed diagnosis (avg. 10 years) [4][14]
Economic: High ER utilization (15,000–30,000 annual U.S. visits); productivity losses (~$5,750/year/patient) [9][14]
Humanistic: 56% report anxiety/depression; 63–89% have impaired work/school performance [4][7][9][14]
Therapies
On-demand: IV C1-INH concentrate (e.g., Berinert®), subcutaneous icatibant (bradykinin receptor antagonist), or ecallantide (kallikrein inhibitor) [3][8][13][17]
Short-term prophylaxis: Pre-procedure C1-INH infusion (e.g., Cinryze®) to prevent attack triggers [3][13]
Long-term prophylaxis: Subcutaneous C1-INH (Haegarda®), lanadelumab (monoclonal kallikrein antibody), or oral berotralstat (kallikrein inhibitor) [3][6][18]
Categories: rare allergic disease, rare genetic diseases, rare systemic and rheumatological diseases
Research Papers
509 drug discovery papers about Hereditary angioedema type 1, with 5 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
509 drug discovery papers about Hereditary angioedema type 1, with 5 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-15 | Berotralstat Tolerability and Effectiveness in Hereditary Angioedema: Berolife Study Results.
Berotralstat is a first-line once-daily oral prophylactic treatment for hereditary angioedema (HAE). Berolife was designed to evaluate the tolerability and effectiveness of berotralstat in real-world conditions. Berolife is an open-label, multicenter, observational study conducted in France from September 2021 to January 2024. The primary objective was to assess tolerability, and secondary objectives included characterization of the treated population and assessment of berotralstat effectiveness. HAE attack rate was assessed before and after initiation of berotralstat using the paired Wilcoxon rank-sum test. Altogether, 80 patients were enrolled in the study (75 with HAE-C1INH type 1 or 2 and 5 with HAE-nC1INH) and received at least one dose of berotralstat. At baseline, patients had a mean (standard deviation [SD]) age of 40.0 (17.5) years, and most (67.5%) had received prior long-term prophylaxis treatment. The mean (SD) duration of berotralstat treatment was 11.5 (8.5) months. Treatment-related adverse events (AEs) occurred in 45.0% of patients, with gastrointestinal disorders being the most common (diarrhea: 13.8%, abdominal pain: 12.5%, upper abdominal pain: 7.5%). Importantly, no treatment-related serious AEs were reported. A total of 61 patients were treated with berotralstat for ≥ 6 months and evaluated for effectiveness. At 6 months of treatment, a significant reduction in monthly HAE attack rates was observed (mean [SD]: 0.62 [0.66] vs. mean [SD]: 1.25 [1.10] at baseline; p = 0.001). Berotralstat was generally well tolerated with a tolerability profile consistent with prior clinical trials. Significant reductions in monthly HAE attack rates were observed, confirming its effectiveness in real-world settings.
2026-08-08 | Lanadelumab Use for Hereditary Angioedema Long-Term Prophylaxis Over the Last 7 Years: A Narrative Review of Clinical and Real-World Data.
Hereditary angioedema (HAE) is a rare genetic disease characterized by unpredictable, painful cutaneous and/or subcutaneous swelling attacks; laryngeal attacks can be fatal. For many patients, long-term prophylaxis (LTP) is critical for disease control and quality of life.Lanadelumab, a plasma kallikrein inhibitor, was approved for HAE LTP for adults and adolescents in 2018 and for children aged ≥ 2 years in 2023; it is currently one of the guideline-recommended, first-line LTP options. By integrating 7 years of cumulative clinical trial and real-world data, this narrative review summarizes lanadelumab long-term effectiveness and safety in adult, adolescent, and pediatric HAE populations. Outcomes in 41 peer-reviewed publications were evaluated, including 5 clinical trials involving 262 lanadelumab-treated patients and 28 real-world studies comprising ~ 700 patients. Across clinical trials, lanadelumab reduced attack rates by up to 100%, with an average of 24.9-27.3 patient-reported attack-free days per 28-day period. These findings were largely corroborated by real-world data, including 2 large observational studies with > 100 patients each. Patient-reported disease control and health-related quality of life improved consistently across both settings. The main treatment-related adverse events across studies were injection site reactions. Treatment persistence was generally high in clinical practice. Unmet needs remain for specific populations, including pregnant or lactating patients and those without access to guideline-recommended LTP. Future research should address real-world outcomes in pediatric patients, extended dosing intervals in well-controlled disease, transitions from other LTP therapies, and cost-effectiveness. Overall, sustained effectiveness, safety, and quality-of-life benefits of lanadelumab reinforce its role as a cornerstone of HAE management.
2026-08-07 | Sustained Effectiveness of Lanadelumab in Preventing Hereditary Angioedema Attacks: The ENABLE Study.
Lanadelumab has been approved for hereditary angioedema (HAE) long-term prophylaxis since 2018. The Phase 4, prospective ENABLE Study (NCT04130191) evaluated the long-term effectiveness and safety of lanadelumab in clinical practice across Europe and the Middle East. Patients with HAE aged ≥ 12 years initiating lanadelumab treatment (300 mg every 2 weeks) per approved product labeling were recruited from Austria, Germany, Israel, Italy, Kuwait, Spain, and Switzerland and followed for up to 36 months (± 30 days). The primary objective was to evaluate lanadelumab effectiveness for HAE attack prevention. Safety and patient-reported health-related quality of life (HRQoL) were also evaluated. Outcomes were analyzed in 138 patients (mean [range] age: 41.0 [14-79] years; 62.3% female; 92.0% HAE-C1INH-Type1), of whom > 60% extended dosing intervals by Month 12. Over a mean ± SD treatment duration of 28.6 ± 9.8 months, mean ± SD patient-reported HAE attack rate decreased from 3.88 ± 3.43 attacks/month pre-lanadelumab to 0.30 ± 0.53 attacks/month (mean decrease, 84% [median 96%]). The incidence-rate ratio was 0.07 (95% CI: 0.06-0.10), reflecting a 93% reduction from modeled pre-lanadelumab rates. Overall, 95/138 patients reported treatment-emergent adverse events (TEAEs); most were unrelated to lanadelumab (82.3%). Of the 17.7% of TEAEs considered treatment-related, injection-site reactions, headache, fatigue, and asthenia occurred in > 1 patient. Before lanadelumab initiation, most patients reported moderate-to-large HRQoL impairments; clinically meaningful improvements were observed 1 month after lanadelumab initiation and sustained throughout the study. Real-world data from ENABLE demonstrated long-term effectiveness of lanadelumab in patients with HAE aged ≥ 12 years and a safety profile consistent with previous clinical studies.
2026-08-06 | A plain language summary of oral berotralstat for preventive treatment of hereditary angioedema attacks in children: early safety and efficacy results of the ongoing APeX-P study
What is this summary about? This plain language summary describes the interim results (early findings) of an ongoing study called APeX-P, which was published in the Annals of Allergy, Asthma & Immunology journal in 2025. The study looked at berotralstat, an oral (taken by mouth) medication, as a treatment option for hereditary angioedema (HAE) in children. HAE is a rare genetic disease that causes episodes of swelling (attacks) in different parts of the body, which can be serious. Attacks in the tongue and throat can be life-threatening. Berotralstat is taken once a day. Before the APeX-P study, the medication was approved in several countries to help prevent HAE attacks in people aged 12 and older. Berotralstat is now approved for use in people aged 2 and older in the United States. The APeX-P study researchers looked at which doses of berotralstat are appropriate for children aged 2 to under age 12, how children tolerated the medication, and how well berotralstat helps to prevent HAE attacks. The study also assessed children’s experiences and burdens with HAE. What were the results? Most of the children participating in the APeX-P study started having symptoms of HAE before they were 6 years old. Before beginning the study, children experienced burden because of HAE attacks, including missing school and needing emergency medical care because of their symptoms. After taking berotralstat for 12 weeks, children had fewer HAE attacks. The lower rate of attacks continued for up to 48-weeks (about 1 year—the study was still ongoing). This meant that children had fewer days with HAE symptoms. During the first 12 weeks of treatment with berotralstat, 3 HAE attacks (across all children in the study) needed medical care in a doctor’s office, clinic, or hospital. This need for medical care was 86% less than the 22 attacks needing medical care in the 12 weeks before the children started taking the medication. Most children in the study experienced at least 1 side effect after taking berotralstat; only 2 side effects (mild nausea or ‘feeling queasy’ and moderate headache) in 2 children were considered to be caused by the medication. Side effects were mild to moderate except in 1 patient who had an accident and a broken arm that was not caused by the medication. The most common side effects included a common cold, upper respiratory infection (in the nose, throat, or sinuses), or headache. What do the results mean? In the APeX-P study, children taking berotralstat tolerated the treatment well. The interim results show that berotralstat prevented attacks from HAE in young children. How to say (download PDF and double click sound icon to play sound)… APeX-P: AY-peks-pee Berotralstat: bear-oh-TRAL-stat Bradykinin: bray-DEE-ki-nin Hereditary angioedema: huh-REH-duh-tree AN-jee-oh-eh-DEE-muh Kallikrein: kal-uh-KREE-in Prophylaxis: pro-fuh-LACK-sis Angioedema: Swelling in the tissue under the skin. Genetic disease: Diseases caused by changes in a person’s DNA that can develop spontaneously or be passed on from parents to children. Tolerated: To handle a medication without having side effects that are serious or bothersome, or that are manageable enough for patients to continue taking the treatment. This is an abstract of the Plain Language Summary of Publication article. View the full Plain Language Summary PDF of this article to read the full-text Link to original article here
2026-08-05 | Diagnostic delay, SERPING1 allelic heterogeneity, and real-world lanadelumab prophylaxis in Chinese patients with hereditary angioedema due to C1 inhibitor deficiency
Background Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a rare and potentially life-threatening bradykinin-mediated disorder most commonly associated with pathogenic variants in SERPING1 . Data from Chinese patients remain limited, particularly regarding diagnostic delay, SERPING1 allelic heterogeneity, and real-world use of lanadelumab prophylaxis. Methods In this single-center retrospective observational study, we reviewed 10 consecutive unrelated index patients with confirmed HAE-C1INH managed at Henan Provincial People’s Hospital from January 2022 to May 2026. Clinical data, complement results, and SERPING1 Sanger sequencing findings were analyzed. Variants were classified according to ACMG/AMP criteria. Seven patients received lanadelumab long-term prophylaxis. Annualized attack rates and Angioedema Control Test scores before and during prophylaxis were compared using the Wilcoxon signed-rank test. Results The cohort included 6 females and 4 males, with a mean age of 32.8 ± 9.9 years. Nine patients had HAE-C1INH type 1 and one had type 2. The mean age at symptom onset was 21.7 ± 11.1 years, and the mean diagnostic delay was 9.4 ± 7.0 years. All patients had recurrent peripheral edema, 7 had abdominal attacks, and 6 had facial and/or laryngeal involvement. One patient required emergency tracheotomy. Serum C4 was reduced during attacks in all patients, and C1q levels were normal. Ten distinct heterozygous SERPING1 variants were identified, including 3 frameshift variants, 6 missense variants, and 1 in-frame deletion. Among the 7 patients receiving lanadelumab, the median annualized attack rate decreased from 11 (IQR, 7–23) to 0 (IQR, 0–1) attacks/year, and the median AECT score increased from 3 (IQR, 2–4) to 13 (IQR, 13–13). No serious adverse events were recorded. Conclusions This single-center retrospective study showed substantial diagnostic delay, marked SERPING1 allelic heterogeneity, and favorable real-world outcomes with lanadelumab prophylaxis in Chinese patients with HAE-C1INH. Earlier complement testing and access to appropriate genetic testing may shorten diagnostic delay. Larger prospective studies are needed to define individualized long-term prophylaxis strategies in Chinese patients.
2026-08-15 | Berotralstat Tolerability and Effectiveness in Hereditary Angioedema: Berolife Study Results.
Berotralstat is a first-line once-daily oral prophylactic treatment for hereditary angioedema (HAE). Berolife was designed to evaluate the tolerability and effectiveness of berotralstat in real-world conditions. Berolife is an open-label, multicenter, observational study conducted in France from September 2021 to January 2024. The primary objective was to assess tolerability, and secondary objectives included characterization of the treated population and assessment of berotralstat effectiveness. HAE attack rate was assessed before and after initiation of berotralstat using the paired Wilcoxon rank-sum test. Altogether, 80 patients were enrolled in the study (75 with HAE-C1INH type 1 or 2 and 5 with HAE-nC1INH) and received at least one dose of berotralstat. At baseline, patients had a mean (standard deviation [SD]) age of 40.0 (17.5) years, and most (67.5%) had received prior long-term prophylaxis treatment. The mean (SD) duration of berotralstat treatment was 11.5 (8.5) months. Treatment-related adverse events (AEs) occurred in 45.0% of patients, with gastrointestinal disorders being the most common (diarrhea: 13.8%, abdominal pain: 12.5%, upper abdominal pain: 7.5%). Importantly, no treatment-related serious AEs were reported. A total of 61 patients were treated with berotralstat for ≥ 6 months and evaluated for effectiveness. At 6 months of treatment, a significant reduction in monthly HAE attack rates was observed (mean [SD]: 0.62 [0.66] vs. mean [SD]: 1.25 [1.10] at baseline; p = 0.001). Berotralstat was generally well tolerated with a tolerability profile consistent with prior clinical trials. Significant reductions in monthly HAE attack rates were observed, confirming its effectiveness in real-world settings.
2026-08-08 | Lanadelumab Use for Hereditary Angioedema Long-Term Prophylaxis Over the Last 7 Years: A Narrative Review of Clinical and Real-World Data.
Hereditary angioedema (HAE) is a rare genetic disease characterized by unpredictable, painful cutaneous and/or subcutaneous swelling attacks; laryngeal attacks can be fatal. For many patients, long-term prophylaxis (LTP) is critical for disease control and quality of life.Lanadelumab, a plasma kallikrein inhibitor, was approved for HAE LTP for adults and adolescents in 2018 and for children aged ≥ 2 years in 2023; it is currently one of the guideline-recommended, first-line LTP options. By integrating 7 years of cumulative clinical trial and real-world data, this narrative review summarizes lanadelumab long-term effectiveness and safety in adult, adolescent, and pediatric HAE populations. Outcomes in 41 peer-reviewed publications were evaluated, including 5 clinical trials involving 262 lanadelumab-treated patients and 28 real-world studies comprising ~ 700 patients. Across clinical trials, lanadelumab reduced attack rates by up to 100%, with an average of 24.9-27.3 patient-reported attack-free days per 28-day period. These findings were largely corroborated by real-world data, including 2 large observational studies with > 100 patients each. Patient-reported disease control and health-related quality of life improved consistently across both settings. The main treatment-related adverse events across studies were injection site reactions. Treatment persistence was generally high in clinical practice. Unmet needs remain for specific populations, including pregnant or lactating patients and those without access to guideline-recommended LTP. Future research should address real-world outcomes in pediatric patients, extended dosing intervals in well-controlled disease, transitions from other LTP therapies, and cost-effectiveness. Overall, sustained effectiveness, safety, and quality-of-life benefits of lanadelumab reinforce its role as a cornerstone of HAE management.
2026-08-07 | Sustained Effectiveness of Lanadelumab in Preventing Hereditary Angioedema Attacks: The ENABLE Study.
Lanadelumab has been approved for hereditary angioedema (HAE) long-term prophylaxis since 2018. The Phase 4, prospective ENABLE Study (NCT04130191) evaluated the long-term effectiveness and safety of lanadelumab in clinical practice across Europe and the Middle East. Patients with HAE aged ≥ 12 years initiating lanadelumab treatment (300 mg every 2 weeks) per approved product labeling were recruited from Austria, Germany, Israel, Italy, Kuwait, Spain, and Switzerland and followed for up to 36 months (± 30 days). The primary objective was to evaluate lanadelumab effectiveness for HAE attack prevention. Safety and patient-reported health-related quality of life (HRQoL) were also evaluated. Outcomes were analyzed in 138 patients (mean [range] age: 41.0 [14-79] years; 62.3% female; 92.0% HAE-C1INH-Type1), of whom > 60% extended dosing intervals by Month 12. Over a mean ± SD treatment duration of 28.6 ± 9.8 months, mean ± SD patient-reported HAE attack rate decreased from 3.88 ± 3.43 attacks/month pre-lanadelumab to 0.30 ± 0.53 attacks/month (mean decrease, 84% [median 96%]). The incidence-rate ratio was 0.07 (95% CI: 0.06-0.10), reflecting a 93% reduction from modeled pre-lanadelumab rates. Overall, 95/138 patients reported treatment-emergent adverse events (TEAEs); most were unrelated to lanadelumab (82.3%). Of the 17.7% of TEAEs considered treatment-related, injection-site reactions, headache, fatigue, and asthenia occurred in > 1 patient. Before lanadelumab initiation, most patients reported moderate-to-large HRQoL impairments; clinically meaningful improvements were observed 1 month after lanadelumab initiation and sustained throughout the study. Real-world data from ENABLE demonstrated long-term effectiveness of lanadelumab in patients with HAE aged ≥ 12 years and a safety profile consistent with previous clinical studies.
2026-08-06 | A plain language summary of oral berotralstat for preventive treatment of hereditary angioedema attacks in children: early safety and efficacy results of the ongoing APeX-P study
What is this summary about? This plain language summary describes the interim results (early findings) of an ongoing study called APeX-P, which was published in the Annals of Allergy, Asthma & Immunology journal in 2025. The study looked at berotralstat, an oral (taken by mouth) medication, as a treatment option for hereditary angioedema (HAE) in children. HAE is a rare genetic disease that causes episodes of swelling (attacks) in different parts of the body, which can be serious. Attacks in the tongue and throat can be life-threatening. Berotralstat is taken once a day. Before the APeX-P study, the medication was approved in several countries to help prevent HAE attacks in people aged 12 and older. Berotralstat is now approved for use in people aged 2 and older in the United States. The APeX-P study researchers looked at which doses of berotralstat are appropriate for children aged 2 to under age 12, how children tolerated the medication, and how well berotralstat helps to prevent HAE attacks. The study also assessed children’s experiences and burdens with HAE. What were the results? Most of the children participating in the APeX-P study started having symptoms of HAE before they were 6 years old. Before beginning the study, children experienced burden because of HAE attacks, including missing school and needing emergency medical care because of their symptoms. After taking berotralstat for 12 weeks, children had fewer HAE attacks. The lower rate of attacks continued for up to 48-weeks (about 1 year—the study was still ongoing). This meant that children had fewer days with HAE symptoms. During the first 12 weeks of treatment with berotralstat, 3 HAE attacks (across all children in the study) needed medical care in a doctor’s office, clinic, or hospital. This need for medical care was 86% less than the 22 attacks needing medical care in the 12 weeks before the children started taking the medication. Most children in the study experienced at least 1 side effect after taking berotralstat; only 2 side effects (mild nausea or ‘feeling queasy’ and moderate headache) in 2 children were considered to be caused by the medication. Side effects were mild to moderate except in 1 patient who had an accident and a broken arm that was not caused by the medication. The most common side effects included a common cold, upper respiratory infection (in the nose, throat, or sinuses), or headache. What do the results mean? In the APeX-P study, children taking berotralstat tolerated the treatment well. The interim results show that berotralstat prevented attacks from HAE in young children. How to say (download PDF and double click sound icon to play sound)… APeX-P: AY-peks-pee Berotralstat: bear-oh-TRAL-stat Bradykinin: bray-DEE-ki-nin Hereditary angioedema: huh-REH-duh-tree AN-jee-oh-eh-DEE-muh Kallikrein: kal-uh-KREE-in Prophylaxis: pro-fuh-LACK-sis Angioedema: Swelling in the tissue under the skin. Genetic disease: Diseases caused by changes in a person’s DNA that can develop spontaneously or be passed on from parents to children. Tolerated: To handle a medication without having side effects that are serious or bothersome, or that are manageable enough for patients to continue taking the treatment. This is an abstract of the Plain Language Summary of Publication article. View the full Plain Language Summary PDF of this article to read the full-text Link to original article here
2026-08-05 | Diagnostic delay, SERPING1 allelic heterogeneity, and real-world lanadelumab prophylaxis in Chinese patients with hereditary angioedema due to C1 inhibitor deficiency
Background Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a rare and potentially life-threatening bradykinin-mediated disorder most commonly associated with pathogenic variants in SERPING1 . Data from Chinese patients remain limited, particularly regarding diagnostic delay, SERPING1 allelic heterogeneity, and real-world use of lanadelumab prophylaxis. Methods In this single-center retrospective observational study, we reviewed 10 consecutive unrelated index patients with confirmed HAE-C1INH managed at Henan Provincial People’s Hospital from January 2022 to May 2026. Clinical data, complement results, and SERPING1 Sanger sequencing findings were analyzed. Variants were classified according to ACMG/AMP criteria. Seven patients received lanadelumab long-term prophylaxis. Annualized attack rates and Angioedema Control Test scores before and during prophylaxis were compared using the Wilcoxon signed-rank test. Results The cohort included 6 females and 4 males, with a mean age of 32.8 ± 9.9 years. Nine patients had HAE-C1INH type 1 and one had type 2. The mean age at symptom onset was 21.7 ± 11.1 years, and the mean diagnostic delay was 9.4 ± 7.0 years. All patients had recurrent peripheral edema, 7 had abdominal attacks, and 6 had facial and/or laryngeal involvement. One patient required emergency tracheotomy. Serum C4 was reduced during attacks in all patients, and C1q levels were normal. Ten distinct heterozygous SERPING1 variants were identified, including 3 frameshift variants, 6 missense variants, and 1 in-frame deletion. Among the 7 patients receiving lanadelumab, the median annualized attack rate decreased from 11 (IQR, 7–23) to 0 (IQR, 0–1) attacks/year, and the median AECT score increased from 3 (IQR, 2–4) to 13 (IQR, 13–13). No serious adverse events were recorded. Conclusions This single-center retrospective study showed substantial diagnostic delay, marked SERPING1 allelic heterogeneity, and favorable real-world outcomes with lanadelumab prophylaxis in Chinese patients with HAE-C1INH. Earlier complement testing and access to appropriate genetic testing may shorten diagnostic delay. Larger prospective studies are needed to define individualized long-term prophylaxis strategies in Chinese patients.
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Drug Discovery Landscape
1 orphan drug designation for Hereditary angioedema type 1.
1 orphan drug designation for Hereditary angioedema type 1.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
C1-inhibitor | proteins | FDA | 1990-08-30 | — | Baxter Healthcare Corp. |
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