Prophylaxis Of Hereditary Angioedema Research Articles

Long-term safety and efficacy of garadacimab for preventing hereditary angioedema attacks: Phase 3 open-label extension study.

Hereditary angioedema (HAE) is a chronic, unpredictable disease. Long-term prophylactic treatments that offer durable efficacy, safety, and convenience are required to assist patients in achieving complete disease control, per international guidelines. We report an interim analysis of an ongoing phase 3 (VANGUARD) open-label extension (OLE) study evaluating the long-term safety and efficacy of garadacimab for HAE prophylaxis. Adults and adolescents aged ≥12 years with HAE previously participating in phase 2 and pivotal phase 3 (VANGUARD) studies were rolled over to an OLE, alongside newly enrolled patients. Patients received garadacimab 200 mg subcutaneously, once monthly for ≥12 months. The primary endpoint was treatment-emergent adverse events (TEAEs) in patients with C1 inhibitor deficiency/dysfunction. At data cut-off (February 13, 2023; N = 161), median (interquartile range) exposure was 13.8 months (11.9-16.3). For the primary endpoint, 133/159 patients experienced ≥1 TEAE (524 events), equivalent to 0.23 events/administration and 2.84 events/patient-year. Garadacimab-related TEAEs (13% of patients, 52 events) were most commonly injection-site reactions (ISRs). No deaths occurred. One patient discontinued treatment due to garadacimab-related moderate ISR. Most TEAEs were mild/moderate; three events were serious (COVID-19, two events; abdominal HAE attack, one event) and not garadacimab related. No abnormal bleeding, thromboembolic, severe hypersensitivity, or anaphylactic events were observed. Mean HAE attack rate decreased by 95% from the run-in period; 60% of patients were attack-free. Almost all patients (93%) rated their response to garadacimab as "good" or "excellent." Garadacimab has a favorable safety profile suitable for long-term use and provides durable protection against HAE attacks.

Assessment of HAE prophylaxis transition from androgen therapy to berotralstat: A subset analysis of the APeX-S trial

BackgroundGiven the recent approval of oral berotralstat in several countries for hereditary angioedema (HAE) prophylaxis, transition from long-term androgens to berotralstat may occur in clinical practice. The open-label, Phase II APeX-S trial provided an opportunity to assess the safety and effectiveness of berotralstat in patients previously treated with differing durations of androgens and shorter transition periods. Therefore, we examined the safety, effectiveness, and impact on quality of life of berotralstat after prior androgen use in patients from the APeX-S trial. Alanine aminotransferase (ALT) elevations were also examined because of the association with androgen exposure and hepatic function impairment. MethodsWe conducted an analysis of a subset of 39 patients from the APeX-S trial aged ≥12 years with HAE due to C1 inhibitor deficiency (HAE-C1-INH) with prior androgen use who discontinued androgen therapy within <60 days of receiving berotralstat. Patients received daily berotralstat (150 mg) and were divided into subgroups for this analysis based on time between androgen discontinuation and berotralstat commencement (<14 days versus 14 to <60 days). ResultsBerotralstat was generally well tolerated, with nasopharyngitis (21%), upper respiratory tract infection (15%), nausea (15%), diarrhea (15%), and abdominal pain (10%) being the most common adverse events occurring in ≥10% of the total subset. Only 7/145 (5%) of all APeX-S study patients with a prior history of androgen therapy experienced ALT elevations, 6 of which were grade 3 or 4 toxicities. All 7 patients recovered without sequelae and belonged to the subgroup of patients who transitioned <14 days after discontinuing androgens (n = 18). A reduction in monthly attack rate versus Month 1 was observed over 12 months for all patients who transitioned from prior androgen therapy to berotralstat prophylaxis in under 60 days, irrespective of duration of prior androgen therapy or timing of transition (N = 39). Similarly, meaningful patient-reported improvements from both Angioedema Quality of Life Questionnaire and Treatment Satisfaction Questionnaire for Medication scores were achieved, with a sustained benefit shown over the berotralstat treatment period. ConclusionsBerotralstat treatment led to sustained HAE symptom control irrespective of duration of prior androgen therapy or timing of transition. Most patients safely transitioned from long-term androgens to berotralstat. Although occurring in a small group of patients, liver-related adverse events following berotralstat treatment may be associated with a shorter androgen washout period, but further research is required to confirm this. Clinical trial registrationNCT03472040. Retrospectively registered March 21, 2018.

Long-term HAE Prophylaxis with Berotralstat Is Well Tolerated and Effective: Analysis for the APeX-S Study

Berotralstat is a first-line once-daily oral prophylaxis for hereditary angioedema (HAE). We report the final long-term safety and effectiveness of berotralstat over 96 weeks for patients enrolled in APeX-S.

Hereditary angioedema and COVID-19 during pregnancy: Two case reports

Hereditary angioedema and COVID-19 during pregnancy: Two case reports

Benefits and Harms of Treatment and Preventive Interventions for Hereditary Angioedema: Protocol for a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: Hereditary angioedema (HAE) is a rare genetic disease that can lead to potentially life-threatening airway attacks. Although novel therapies for HAE treatment have become available over the past decades, a comparison of all available treatments has not yet been conducted. As such, we will perform a systematic review and network meta-analysis to identify the best evidence-based treatments for the management of acute attacks and prophylaxis of HAE. Methods: This study will include both parallel and crossover randomized controlled trials that have investigated prevention or treatment strategies for HAE attacks. We will search electronic databases, including Medline, Embase, PubMed, Cochrane Library, Scopus, and CINAHL, from inception with no language restrictions. Potential trials will be supplemented through a gray literature search. The process of study screening, selection, data extraction, risk-of-bias assessment, certainty assessment and classification of treatments will be performed independently by a pair of reviewers. Any discrepancy will be addressed through team discussion. A two-step approach of pairwise and network meta-analysis will be performed. The summarized effect estimates of direct and indirect treatment comparisons will be pooled using DerSimonion–Laird random-effects models. The incoherence assumption, in terms of the consistency of direct and indirect effects, will be assessed. An evidence-based synthesis will be performed, based on the magnitudes of effect size, evidence certainty, and ranking of treatment effects, with respect to treatment benefits and harms. Discussion: This systematic review and network meta-analysis will summarize evidence-based conclusions with respect to the ratio of benefits and harms arising from interventions for the treatment of acute attacks and prophylaxis of HAE. Evidence from this network estimate could promote the rational use of interventions among people living with HAE in clinical practice settings. PROSPERO registration number: CRD42021251367.

A review of oral kallikrein inhibitor berotralstat for hereditary angioedema.

Orladeyo, a once-daily oral formulation of berotralstat (formerly BCX-7353), is a novel oral small-molecule drug developed by BioCryst Pharmaceuticals for the prevention of hereditary angioedema (HAE) attacks. It was first approved by the U.S. Food and Drug Administration (FDA) in 2020, and in 2021 also gained approval for marketing in Japan and the European Union. Preclinical and phase I studies showed promising efficacy and safety, and several multicenter international Angioedema Prophylaxis (APeX) phase II and III trials have since been initiated to further evaluate berotralstat. The ongoing phase III APeX-2 trial showed a 67% reduction in HAE attacks at the standard 150-mg dosing. Mild to moderate gastrointestinal side effects are most commonly seen and minimal serious adverse effects have been reported. Other first-line therapies for HAE prophylaxis rely on burdensome subcutaneous or intravenous routes. Thus far berotralstat has shown to be effective and well tolerated for HAE prophylaxis with the convenience of once-daily oral dosing.

Orladeyo (Berotralstat): A Novel Oral Therapy for the Prevention of Hereditary Angioedema.

The purpose of this article is to review the available trials that led to the Food and Drug Administration (FDA) approval of berotralstat, an oral kallikrein inhibitor, for the prevention of hereditary angioedema (HAE) attacks. PubMed and ClincalTrials.gov were searched using key term berotralstat to identify phase III clinical trials related to the FDA approval of berotralstat from April 2018 to May 2021. Trials selected were those that influenced the FDA approval of berotralstat or provided novel information regarding the safety and efficacy of this therapy in the treatment of HAE. Both APeX-2 and ApeX-J found clinically significant benefit with berotralstat 150 mg daily for reduction in HAE attacks when compared with placebo (1.31 vs 2.35, P < 0.001, and 1.11 vs 2.18, P < 0.001, attacks in the APeX-2 and APeX-J trials, respectively). APeX-2 also showed a statistically significant benefit for berotralstat 110 mg daily (1.65 vs 2.35 attacks [1.65 attacks, P = 0.024]). An advantage berotralstat has over the other approved therapies is that it is administered orally, which may garner patient preference because of ease of administration. Berotralstat has also shown a potential benefit in reducing the need for standard-of-care treatment for HAE attacks, which has not been studied with alternative agents. Berotralstat 150 mg daily has been proven safe and effective in clinical studies and appears to be a viable oral alternative to parenteral medications currently used in HAE prophylaxis.

Recurrent and acute abdominal pain as the main clinical manifestation in patients with hereditary angioedema.

Background: Hereditary angioedema (HAE) is a rare disease that often leads to misdiagnosis. The delay of diagnosis is > 10 years in China. Recurrent and acute abdominal pain is one of the common symptoms of HAE. Because of the high misdiagnosis rate, it usually results in unnecessary surgical procedures. This study focused on the clinical symptoms and management of HAE-related abdominal attacks in Chinese patients to provide some new insight for the emergency department (ED) physicians and gastroenterologists. Methods: A Web-based survey was conducted among 107 patients with HAE from 94 unrelated families. Detailed questions with respect to the abdominal attacks were asked, including the frequency, symptoms, and duration before and after confirmed diagnosis. The demographic characteristics, diagnosis process, and treatment outcomes were also included. Results: Approximately 70% of the patients with HAE presented with abdominal symptoms during the onset of edema, mostly characterized by pain (94.8%), nausea (83.1%), vomiting (83.1%), diarrhea (59.7%), and constipation (23.4%). The patients were easily misdiagnosed as having gastroenteritis (35.1%) and appendicitis (10.4%), and 24.7% of them received unnecessary appendectomy or laparotomy. Danazol, a widely used drug for long-term prophylaxis of HAE in China, can reduce the attack frequency and alleviate the abdominal symptoms, but the adverse effects are also significant and more severe in women. Conclusions: Abdominal symptoms are common and important clinical features of HAE but are easily confused with other gastrointestinal diseases. ED physicians and gastroenterologists should consider HAE when patients experience recurrent and unexplained abdominal pain. Proper medical treatment should be administered in a timely manner if an HAE diagnosis is confirmed and efforts are required to increase access in China to medications both for on-demand treatment and long-term prophylaxis.

Berotralstat Reduces Use of On-demand Medication in Hereditary Angioedema (HAE) Patients Previously Treated with Prophylactic Therapies

The goal of HAE prophylaxis is to minimize the number of HAE attacks and the associated disease burden, including treatment with on-demand medications. Berotralstat is an oral once-daily selective plasma kallikrein inhibitor that has been shown to reduce attack frequency in a Phase 3 study (NCT03485911). This analysis evaluates reduction in on-demand medication in patients with prior prophylaxis. A double-blind, placebo-controlled study (APeX-2) randomized patients to berotralstat 110 mg (n=41):150 mg (n=40):placebo (n=40) daily for 24 weeks in Part 1. For this post hoc analysis, patients were grouped according to their prior prophylaxis: prior C1 esterase inhibitor (C1-INH), prior androgen, or no prior prophylactic medication. Prior C1-INH and prior androgen categories are not mutually exclusive. In patients with prior C1-INH prophylaxis (berotralstat 150 mg n=21; placebo n=16), the rate of use of on-demand treatment was significantly reduced vs placebo (-59.2%, p=0.002). Similar reductions were noted for patients with prior androgen use (berotralstat 150 mg n=22; placebo n=25) (-51.8%; p=0.004) and in patients without prior prophylaxis (berotralstat 150 mg n=10; placebo n=10) (-71.2%; p=0.019). The rate reduction corresponds to approximately 2.2 fewer doses of on-demand medication per month compared to placebo in patients with prior C1-INH use, 1.6 for those with prior androgen use, and 1.4 for those with no prior prophylaxis. Prophylactic treatment with oral berotralstat 150 mg resulted in significant reductions in on-demand medication compared to placebo irrespective of prior prophylactic treatment.

P154 SAFETY AND TOLERABILITY OF ONCE-DAILY ORAL KALLIKREIN INHIBITOR BCX7353 IN PHASE 3 APEX-2 HAE STUDY

Hereditary angioedema (HAE) is a potentially life-threatening disorder in which C1-esterase inhibitor, which inhibits kallikrein, is low or non-functioning. All current targeted prophylactic treatments for HAE are parenteral. The safety profile of BCX7353, a novel oral kallikrein inhibitor for HAE prophylaxis, was evaluated in a Phase 3 trial (APeX-2; NCT03485911).

Indirect comparison of intravenous vs. subcutaneous C1-inhibitor placebo-controlled trials for routine prevention of hereditary angioedema attacks

IntroductionFor prophylaxis of hereditary angioedema (HAE) attacks, replacement therapy with human C1-inhibitor (C1-INH) treatment is approved and available as intravenous [C1-INH(IV)] (Cinryze®) and subcutaneous [C1-INH(SC)] HAEGARDA® preparations. In the absence of a head-to-head comparative study of the two treatment modalities, an indirect comparison of data from 2 independent but similar clinical trials was undertaken.MethodsTwo similar randomized, double-blind, placebo-controlled, crossover studies were identified which evaluated either C1-INH(SC) (COMPACT; NCT01912456; 16 weeks) or C1-INH(IV) (CHANGE; NCT01005888; 14 weeks) vs. placebo (on-demand treatment only) for routine prevention of HAE attacks. Individual patient data from each trial were used to conduct an indirect comparison of treatment effects. Attack reductions (absolute and percent of mean/median number of monthly HAE attacks reduction over placebo) were compared between the two C1-INH formulations at approved/recommended doses: C1-INH(SC) 60 IU/kg twice weekly (n = 45) and 1000 U of C1-INH(IV) twice weekly (n = 22). Point estimates were adjusted using mixed and quantile regression models that controlled for study design.ResultsThe absolute mean monthly numbers of HAE attack reductions were 3.6 (95% CI 2.9, 4.2) for C1-INH(SC) 60 IU/kg vs. placebo and 2.3 (1.4, 3.3) for C1-INH(IV) vs. placebo; between-product difference, 1.3 (0.1, 2.4; P = 0.034). The mean percent reduction in monthly attack rate was significantly greater with C1-INH(SC) as compared with C1-INH(IV) (84% vs. 51%; P < 0.001). The percentages of subjects experiencing ≥ 50%, ≥ 70%, and ≥ 90% reductions in monthly HAE attack rates versus placebo were significantly higher with C1-INH(SC) 60 IU/kg as compared to C1-INH(IV) 1000 U (≥ 50% reduction: 91% vs. 50%, odds ratio [OR] = 10.33, P = 0.003; ≥ 70% reduction: 84% vs. 46%, OR = 6.19, P = 0.005; ≥ 90% reduction: 57% vs. 18%, OR = 6.04, P = 0.007).ConclusionWithin the limitations of an indirect study comparison, this analysis suggests greater attack reduction with twice-weekly C1-INH(SC) 60 IU/kg as compared to twice-weekly C1-INH(IV) 1000 U for the routine prevention of HAE attacks.

Long-term safety outcomes of prekillikrein (Fletcher factor) deficiency: A systematic literature review of case reports.

Hereditary prekallikrein (Fletcher factor) deficiency is a rare condition characterized by a prolonged activated partial thromboplastin time. Inhibitors of plasma kallikrein have recently been approved for prophylaxis of hereditary angioedema and are under investigation for use in other indications. We attempted to conservatively assess the impact of long-term inhibition of this pathway by reviewing reportedcomorbidities in patients with hereditary prekallikrein deficiency. We searched several medical literature databases for publications that reported data from patients with hereditaryprekallikrein deficiency (<10% of normal and/or shortening of activated partial thromboplastin time on increased incubationtime). Data reporting of cardiovascular, bleeding, and autoimmune-related diseases were extracted. Of 1966 publications screened, 45 publications (which represented 53 patients with prekallikrein deficiency) wereincluded. Among 53 identified patients with prekallikrein deficiency, 25 were explicitly defined as asymptomatic, with no comorbidities mentioned in another three cases. Another 16 of the 53 patients were described as having undergone surgery or dental extractions with no complications. Cardiovascular comorbidities were reported in 19 patients, mainly hypertension (9 patients) and cerebrovascular ischemia or stroke (5 patients). Excessive bleeding episodes after surgery were reported in four patients. Autoimmune-related diseases were reported for three patients (two with Graves disease and onewith systemic lupus erythematosus). This review identified patients with hereditary prekallikrein deficiency who reported a spectrum of health outcomes from asymptomatic to infrequent reports of cardiovascular, bleeding, and autoimmune comorbidities. The majority of the reports did not indicate any association between prekallikrein deficiency and comorbidities; however, additional observation is required to confirm the long-term safety of plasma kallikrein inhibition.

LANADELUMAB SAFETY AND IMMUNOGENICITY: RESULTS FROM THE PHASE 3 HELP STUDY

Introduction Lanadelumab, a fully human monoclonal antibody targeting plasma kallikrein, effectively prevented attacks in patients with hereditary angioedema (HAE) in the phase 3 HELP Study (NCT02586805). Methods In HELP, patients ≥12 years with type I/II HAE and ≥1 attack during a 4-week run-in received SC lanadelumab 300 mg q2wks, 300 mg q4wks, 150 mg q4wks, or placebo over 26 weeks. The safety and immunogenicity of repeated doses of lanadelumab were assessed. Results The safety population consisted of 125 patients who received ≥1 dose of study medication; 84 received lanadelumab and 41 received placebo. 78 [92.8%] and 35 [85.4%] patients in lanadelumab and placebo arms completed the study. Treatment emergent AEs (TEAEs) were reported by 76 (90.5%) patients receiving lanadelumab and 31 (75.6%) patients receiving placebo. No serious treatment-related AEs or deaths were reported. One (1.2%) lanadelumab-treated subject had two related hypersensitivity events, one mild and one moderate in severity. Immunogenicity results included ten (11.9%) lanadelumab-treated subjects and 2 (4.9%) placebo-treated subjects with ≥1 treatment-emergent anti-drug antibody (ADA)-positive sample, all at low titers. Two (2.4%) subjects positive for ADA in the 150 mg q4wks arm had low titer neutralizing antibodies. The development of ADA did not impact pharmacokinetics, pharmacodynamics, or clinical response. No safety signals in terms of clinical laboratory tests, vital signs, physical examinations, or ECGs were identified. Conclusions Lanadelumab was generally well tolerated, with few cases of hypersensitivity and low immunogenicity. Together with its efficacy in preventing HAE attacks, lanadelumab may offer patients a novel and well tolerated therapeutic option for HAE prophylaxis.

Recombinant human C1 esterase inhibitor (Conestat alfa) for prophylaxis to prevent attacks in adult and adolescent patients with hereditary angioedema

ABSTRACTIntroduction: Hereditary angioedema (HAE) due to C1 inhibitor (C1-INH) deficiency is a debilitating and potentially lethal disease. Management includes on-demand treatment of angioedema and their prophylaxis. Plasma derived C1-INH is an established treatment for both on demand and prophylaxis of HAE. Conestat alfa is a recombinant form of human C1-INH (rhC1-INH) produced in transgenic rabbits. It has granted drug’s registration as treatment option for acute HAE attacks in adults and adolescents in Europe, America, and other countries. Long-term prophylaxis with rhC1-INH received recent consideration in clinical trials.Areas covered: This review will critically appraise available information about rhC1-INH (conestat alfa) prophylactic treatment in adult and adolescent patients with congenital C1-INH deficiency. Results from a phase II randomized placebo-controlled trial for prophylaxis of severe HAE evidenced positive treatment outcomes for its application, both twice or once weekly.Expert commentary: Phase II clinical studies suggest that rhC1-INH is a viable option for prophylaxis of HAE. Safety and tolerability data are comparable to other available HAE specific drugs, zeroing the possibility for blood-born viral transmission. Sustainability of modern technologies is granting a practically stable and continuous recombinant production process. With other available options, rhC1-INH facilitates tailoring HAE treatment to patients’ needs.

P159 Attacks avoided and cost offsets associated with subcutaneous C1-inhibitor (human) long-term prophylaxis of hereditary angioedema

P159 Attacks avoided and cost offsets associated with subcutaneous C1-inhibitor (human) long-term prophylaxis of hereditary angioedema

OR032 Hereditary angioedema prophylaxis: effect of an online educational intervention among allergist learners

OR032 Hereditary angioedema prophylaxis: effect of an online educational intervention among allergist learners

Patient satisfaction and experience with intravenously administered C1-inhibitor concentrates in the United States

BackgroundHereditary angioedema (HAE) is a rare genetic disorder with substantial morbidity and mortality. Despite expanded choices for effective acute treatment, prophylactic options are more limited. Intravenous C1 esterase inhibitor (C1-INH[IV]) is licensed and used to prevent HAE symptoms. ObjectiveTo better understand patient experiences with using C1-INH(IV), including level of satisfaction and types and frequency of complications. MethodsFifty adult members (≥18 years of age) of the US HAE Association who had HAE type I or II completed a self-administered internet survey. Eligible participants were experiencing at least 1 HAE attack per month and must have been receiving treatment with C1-INH(IV) as prophylaxis or acute therapy. ResultsAlmost all respondents (n = 47; 94%) were using C1-INH(IV) for HAE prophylaxis. Most patients reported administration of C1-INH(IV) through a peripheral vein (n = 34) and 19 were currently (n = 17) or previously (n = 2) using a central venous port. Most respondents (62%) who used a peripheral vein to administer treatment reported having difficulty finding a usable vein or getting the infusion to work properly at least some of the time. Issues accessing veins, exhausted veins, and frequency of attacks were the main reasons physicians recommended ports to respondents. Although ports allow easier administration of therapy, 47% of respondents with ports experienced problems such as occlusion, thrombosis, and infection. Respondents using C1-INH prophylaxis reported a mean of 2.3 attacks per month during the previous 6 months. ConclusionThe survey results identified clinical challenges with IV HAE medication use, including venous access issues and ongoing monthly attack occurrence despite prophylactic C1-INH(IV) administration.

Self-administered C1 esterase inhibitor concentrates for the management of hereditary angioedema: usability and patient acceptance.

Hereditary angioedema (HAE) is a rare genetic disease characterized by episodic subcutaneous or submucosal swelling. The primary cause for the most common form of HAE is a deficiency in functional C1 esterase inhibitor (C1-INH). The swelling caused by HAE can be painful, disfiguring, and life-threatening. It reduces daily function and compromises the quality of life of affected individuals and their caregivers. Among different treatment strategies, replacement with C1-INH concentrates is employed for on-demand treatment of acute attacks and long-term prophylaxis. Three human plasma-derived C1-INH preparations are approved for HAE treatment in the US, the European Union, or both regions: Cinryze®, Berinert®, and Cetor®; however, only Cinryze is approved for long-term prophylaxis. Postmarketing studies have shown that home therapy (self-administered or administered by a caregiver) is a convenient and safe option preferred by many HAE patients. In this review, we summarize the role of self-administered plasma-derived C1-INH concentrate therapy with Cinryze at home in the prophylaxis of HAE.

Case report: follow-up of long term prophylaxis of hereditary angioedema with an alternative attenuated androgenic drug

Background Hereditary Angioedema (HAE) is a disease caused by defective production or function of C1 inhibitor (C1INH) and transmitted by autossomic dominant inheritance pattern. Treatment of HAE is divided into three parts: short-term and long-term prophylaxis, and treatment of acute attacks. The long-term prophylaxis of HAE is aimed at reducing the frequency and severity of acute attacks. This is usually made using attenuated androgens

Hereditary angioedema: epidemiology, management, and role of icatibant

Hereditary angioedema (HAE) is an autosomal dominant, potentially life-threatening condition, manifesting as recurrent and self-limiting episodes of facial, laryngeal, genital, or peripheral swelling with abdominal pain secondary to intra-abdominal edema. The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000, without major sex or ethnic differences. Various treatment options for acute attacks and prophylaxis of HAE are authorized and available in the market, including plasma-derived (Berinert®, Cinryze®, and Cetor®) and recombinant (Rhucin® and Ruconest™) C1 inhibitors, kallikrein inhibitor-ecallantide (Kalbitor®), and bradykinin B2 receptor antagonist-icatibant (Firazyr®). Some of these drugs are used only to treat HAE attacks, whereas others are only approved for prophylactic therapies and all of them have improved disease outcomes due to their different mechanisms of action. Bradykinin and its binding to B2 receptor have been demonstrated to be responsible for most of the symptoms of HAE. Thus icatibant (Firazyr®), a bradykinin B2 receptor antagonist, has proven to be an effective and more targeted treatment option and has been approved for the treatment of acute attacks of HAE. Rapid and stable relief from symptoms of cutaneous, abdominal, or laryngeal HAE attacks has been demonstrated by 30 mg of icatibant in Phase III clinical trials. Self-resolving mild to moderate local site reactions after subcutaneous injection of icatibant were observed. Icatibant is a new, safe, and effective treatment for acute attacks of HAE. HAE has been reported to result in enormous humanistic burden to patients, affecting both physical and mental health, with a negative impact on education, career, and work productivity, and with substantial economic burdens. The timely and proper use of disease-specific treatments could improve patients’ quality of life, reduce the disease-specific morbidity and mortality, and, last but not least, reduce costs associated with hospitalizations and emergency room visits. Therefore, the paradigm of HAE treatment has the potential to evolve significantly, thereby exponentially improving a patient’s quality of life.