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
501 drug discovery papers related to Hereditary angioedema type 1, with 5 first-in-class and 0 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
501 drug discovery papers related to Hereditary angioedema type 1, with 5 first-in-class and 0 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-08 | Donidalorsen for the Treatment of Hereditary Angioedema: A Review of Clinical Studies.
Hereditary angioedema (HAE) is a rare disease characterized by recurrent attacks of severe tissue swelling caused by dysregulation of the kallikrein-kinin system. Donidalorsen is a triantennary N-acetyl galactosamine-conjugated antisense oligonucleotide designed to specifically and reversibly reduce plasma prekallikrein production by binding to plasma prekallikrein messenger RNA in the liver. This report reviews donidalorsen's mechanism of action and data on the pharmacodynamics, efficacy, patient-reported outcomes, and safety of donidalorsen from clinical trials in adolescent and adult participants. In a Phase 1 trial, subcutaneous (SC) administration of donidalorsen led to dose-dependent reductions in plasma prekallikrein concentrations. In a subsequent Phase 2, randomized, placebo-controlled study, donidalorsen 80 mg SC once every 4 weeks (Q4W) for 16 weeks resulted in a 90% mean reduction in monthly HAE attack rate vs placebo, which was sustained for up to 4 years in an open-label extension (OLE). In the Phase 3, randomized, placebo-controlled OASIS-HAE study, patients receiving donidalorsen 80 mg Q4W or once every 8 weeks (Q8W) experienced significant mean reductions in HAE attack rates vs placebo over Weeks 0 to 24 (Q4W: 81%; Q8W: 55%). Mean attack rates were reduced by 87% (Q4W) and 60% (Q8W) vs placebo over Weeks 4 to 24. Reductions in attack rate from OASIS-HAE baseline were sustained for up to 1 year in the OASISplus OLE (Q4W: 94%; Q8W: 95%). A notable study in the clinical program included a cohort of patients who switched from berotralstat, C1 inhibitor, or lanadelumab to donidalorsen for up to 1 year; mean attack rates were reduced by 68% vs baseline (on prior HAE prophylaxis). Donidalorsen treatment improved quality of life at all assessments. Across studies, donidalorsen had an acceptable safety and tolerability profile, with mostly mild to moderate adverse events reported. Overall, the clinical data are promising for donidalorsen as a long-term prophylactic medication for HAE.
2026-07-07 | Living-Donor Kidney Transplantation Between Mother and Son With Clinically Confirmed Hereditary Angioedema.
Hereditary angioedema (HAE) is a rare autosomal dominant disorder resulting from SERPING1-related C1-inhibitor deficiency. Surgical stress and airway manipulation may precipitate life-threatening attacks. Experience with kidney transplantation in patients with HAE remains extremely limited. We describe a 19-year-old male with end-stage kidney disease secondary to congenital obstructive uropathy and nephrolithiasis, who underwent successful living-donor kidney transplantation from his mother, also diagnosed with HAE type I. Because danazol is unavailable in Argentina, both donor and recipient received compounded stanozolol 2 mg daily, starting 5 days preoperatively and continuing for 5 days postoperatively. Fresh frozen plasma (FFP, 10 mL/kg) was administered before extubation to raise C1-inhibitor levels, and icatibant was kept on standby for rescue. Neither donor nor recipient experienced perioperative angioedema. Both had uneventful recoveries, with the recipient maintaining stable graft function over 10 months of follow-up (latest serum creatinine 1.4 mg/dL). This report demonstrates that living-donor kidney transplantation between two individuals affected by HAE can be performed safely with individualized prophylaxis and multidisciplinary coordination.
2026-06-25 | Icatibant for acute hereditary angioedema attacks in pediatric patients: A systematized review.
Background: Hereditary angioedema (HAE) is a rare, potentially life-threatening bradykinin-mediated disorder with limited pediatric treatment options and little comparative evidence. Icatibant, a bradykinin B2 receptor antagonist, has demonstrated efficacy in adults and has emerging evidence in children. Objective: To evaluate and synthesize clinical evidence on the efficacy and safety of icatibant for acute HAE attacks in pediatric patients. Methods: A literature search was performed by using medical literature data bases, clinical trial and research registries, and key journals through January 2026. The primary outcome was the time to onset of symptom relief. Secondary outcomes included the time to minimum symptoms, pain scores, adverse events, and feasibility of self- or caregiver administration. All included studies were nonrandomized, single-arm trials with heterogeneous designs and outcomes definitions; therefore, a meta-analysis was not performed, and all studies were descriptively evaluated. Results: This systematic review identified three clinical studies of icatibant for acute HAE attacks in children ages 0 to 17 years. Three open-label, phase III studies, which included 43 pediatric patients were reviewed. Icatibant demonstrated rapid symptom relief, with a median onset at ∼1 hour and minimum symptoms within 2 hours, although repeated dosing showed variability. Icatibant was well tolerated, with injection-site reactions as the most common adverse events and no serious treatment-related events. Self- or caregiver administration was feasible and effective in adolescents. Conclusion: Icatibant was safe and effective in the pediatric studies, providing rapid symptoms relief and a favorable tolerability profile. Despite limitations from small sample sizes and lack of comparator trials, current evidence supports icatibant as a targeted, practical option for treating acute HAE attacks in children.
2026-07-08 | Donidalorsen for the Treatment of Hereditary Angioedema: A Review of Clinical Studies.
Hereditary angioedema (HAE) is a rare disease characterized by recurrent attacks of severe tissue swelling caused by dysregulation of the kallikrein-kinin system. Donidalorsen is a triantennary N-acetyl galactosamine-conjugated antisense oligonucleotide designed to specifically and reversibly reduce plasma prekallikrein production by binding to plasma prekallikrein messenger RNA in the liver. This report reviews donidalorsen's mechanism of action and data on the pharmacodynamics, efficacy, patient-reported outcomes, and safety of donidalorsen from clinical trials in adolescent and adult participants. In a Phase 1 trial, subcutaneous (SC) administration of donidalorsen led to dose-dependent reductions in plasma prekallikrein concentrations. In a subsequent Phase 2, randomized, placebo-controlled study, donidalorsen 80 mg SC once every 4 weeks (Q4W) for 16 weeks resulted in a 90% mean reduction in monthly HAE attack rate vs placebo, which was sustained for up to 4 years in an open-label extension (OLE). In the Phase 3, randomized, placebo-controlled OASIS-HAE study, patients receiving donidalorsen 80 mg Q4W or once every 8 weeks (Q8W) experienced significant mean reductions in HAE attack rates vs placebo over Weeks 0 to 24 (Q4W: 81%; Q8W: 55%). Mean attack rates were reduced by 87% (Q4W) and 60% (Q8W) vs placebo over Weeks 4 to 24. Reductions in attack rate from OASIS-HAE baseline were sustained for up to 1 year in the OASISplus OLE (Q4W: 94%; Q8W: 95%). A notable study in the clinical program included a cohort of patients who switched from berotralstat, C1 inhibitor, or lanadelumab to donidalorsen for up to 1 year; mean attack rates were reduced by 68% vs baseline (on prior HAE prophylaxis). Donidalorsen treatment improved quality of life at all assessments. Across studies, donidalorsen had an acceptable safety and tolerability profile, with mostly mild to moderate adverse events reported. Overall, the clinical data are promising for donidalorsen as a long-term prophylactic medication for HAE.
2026-07-07 | Living-Donor Kidney Transplantation Between Mother and Son With Clinically Confirmed Hereditary Angioedema.
Hereditary angioedema (HAE) is a rare autosomal dominant disorder resulting from SERPING1-related C1-inhibitor deficiency. Surgical stress and airway manipulation may precipitate life-threatening attacks. Experience with kidney transplantation in patients with HAE remains extremely limited. We describe a 19-year-old male with end-stage kidney disease secondary to congenital obstructive uropathy and nephrolithiasis, who underwent successful living-donor kidney transplantation from his mother, also diagnosed with HAE type I. Because danazol is unavailable in Argentina, both donor and recipient received compounded stanozolol 2 mg daily, starting 5 days preoperatively and continuing for 5 days postoperatively. Fresh frozen plasma (FFP, 10 mL/kg) was administered before extubation to raise C1-inhibitor levels, and icatibant was kept on standby for rescue. Neither donor nor recipient experienced perioperative angioedema. Both had uneventful recoveries, with the recipient maintaining stable graft function over 10 months of follow-up (latest serum creatinine 1.4 mg/dL). This report demonstrates that living-donor kidney transplantation between two individuals affected by HAE can be performed safely with individualized prophylaxis and multidisciplinary coordination.
2026-06-25 | Icatibant for acute hereditary angioedema attacks in pediatric patients: A systematized review.
Background: Hereditary angioedema (HAE) is a rare, potentially life-threatening bradykinin-mediated disorder with limited pediatric treatment options and little comparative evidence. Icatibant, a bradykinin B2 receptor antagonist, has demonstrated efficacy in adults and has emerging evidence in children. Objective: To evaluate and synthesize clinical evidence on the efficacy and safety of icatibant for acute HAE attacks in pediatric patients. Methods: A literature search was performed by using medical literature data bases, clinical trial and research registries, and key journals through January 2026. The primary outcome was the time to onset of symptom relief. Secondary outcomes included the time to minimum symptoms, pain scores, adverse events, and feasibility of self- or caregiver administration. All included studies were nonrandomized, single-arm trials with heterogeneous designs and outcomes definitions; therefore, a meta-analysis was not performed, and all studies were descriptively evaluated. Results: This systematic review identified three clinical studies of icatibant for acute HAE attacks in children ages 0 to 17 years. Three open-label, phase III studies, which included 43 pediatric patients were reviewed. Icatibant demonstrated rapid symptom relief, with a median onset at ∼1 hour and minimum symptoms within 2 hours, although repeated dosing showed variability. Icatibant was well tolerated, with injection-site reactions as the most common adverse events and no serious treatment-related events. Self- or caregiver administration was feasible and effective in adolescents. Conclusion: Icatibant was safe and effective in the pediatric studies, providing rapid symptoms relief and a favorable tolerability profile. Despite limitations from small sample sizes and lack of comparator trials, current evidence supports icatibant as a targeted, practical option for treating acute HAE attacks in children.
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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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