Kalbitor (ecallantide) / Takeda - LARVOL DELTA

Diverse Trial Designs, Populations, and Outcomes: A Systematic Literature Review of Trials for the Treatment of Hereditary Angioedema Attacks. (PubMed, Adv Ther) - "Substantial heterogeneity in trial design, attack eligibility criteria, redosing and rescue protocols, censoring rules, and endpoint definitions limit cross-trial comparability of on-demand HAE therapies. Future comparative efficacy research should prioritize harmonization of endpoint definitions, map across PRO instruments, and adjust for treatment effect modifiers."

Clinical • Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hereditary Angioedema

ON-DEMAND TREATMENTS FOR HEREDITARY ANGIOEDEMA AND HEALTHCARE RESOURCE UTILIZATION IN PEDIATRIC (2-11 YEARS) PATIENTS: A US CLAIMS DATABASE ANALYSIS (ISPOR 2026) - "A standardized dose was defined as one icatibant syringe, one rhC1INH vial, three ecallantide vials, or two pdC1INH (Berinert) vials. On-demand treatment options are limited for the US pediatric HAE population with only IV pdC1INH being FDA-approved. This analysis found that most (62%) pediatric patients had claims of pdC1INH, which contributed 40% of total on-demand doses. This contrasts with icatibant where 24% of patients contributed to the same total on-demand dose share."

Claims database • Clinical • HEOR • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pediatrics

RECENT TRENDS IN ON-DEMAND TREATMENT PRESCRIPTIONS FOR HEREDITARY ANGIOEDEMA: A US CLAIMS DATABASE ANALYSIS (ISPOR 2026) - "OD doses were calculated among patients with ≥1 claims of OD; a standardized OD dose was defined as one icatibant syringe, two rhC1INH vials, three ecallantide vials, or four pdC1INH vials. While overall LTP utilization increased and shifted somewhat toward oral therapy, on-demand treatment utilization remained constant. Current LTP strategies have not eliminated the need for acute intervention, highlighting the continued clinical importance of OD therapy."

Claims database • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Sebetralstat (Ekterly) for treatment of hereditary angioedema attacks. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Barely There But Existent: Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema. (PubMed, Cureus) - "On this occasion, she presented with upper airway swelling secondary to angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema, requiring endotracheal intubation. Initial management in the A&E department, under differential consideration for anaphylaxis and Ludwig's angina, included oxygen via a non-rebreather mask (NRM), intramuscular adrenaline, intravenous dexamethasone, nebulization with Pulmicort, and antibiotic coverage with ceftriaxone and metronidazole...ACEI-induced angioedema is a rare but potentially life-threatening adverse effect of ACEIs, which are widely prescribed for hypertension, heart failure, and chronic kidney disease. A thorough medication history is essential for the timely recognition and management of this condition."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Hypertension • Infectious Disease • Nephrology • Obstructive Sleep Apnea • Renal Disease • Respiratory Diseases • Sleep Disorder

Unmasking an Uncommon Complication of a Common Drug: A Case of Severe Angioedema Post tPA (ATS 2025) - "Given ACEi's associated angioedema risk, his home lisinopril was held...Fresh frozen plasma, Icatibant, Ecallantide, or a C1-esterase inhibitor have been tried in refractory cases. Although angioedema after Tenecteplase administration is a rare complication, providers must maintain a high degree of caution before its administration, especially when patients are on ACEi. As angioedema can evolve rapidly, it may be prudent to prophylactically administer diphenhydramine to high-risk patients such as patients on ACEi."

Clinical • Atrial Fibrillation • Cardiovascular • Diabetes • Dyslipidemia • Hypertension • Ischemic stroke • Metabolic Disorders • Pain • Pruritus

Systematic Literature Review of Recombinant C1 Esterase Inhibitor (rhC1-INH) and Other Products for the On-Demand Treatment of Hereditary Angioedema Attacks (ISPOR 2025) - "Eligible publications included phases 2, 3, and 4 randomized controlled trials (RCTs) and open-label extension (OLE) studies assessing HAE attacks in patients aged ≥12 years with the following interventions: Ruconest ® (conestat alfa), Firazyr ® (icatibant), Kalbitor ® (ecallantide), sebetralstat (KVD900), and Berinert (C1 esterase inhibitor, human). The study populations and end point definitions used in clinical trials assessing acute HAE treatments have changed over time. Key study differences included route of administration, trial setting, time of treatment, attack severity at enrollment, attack location, redosing and rescue therapy criteria, patient-reported outcome assessments, and outcome definitions. Further investigation is warranted to evaluate these differences and determine whether they affected study outcomes."

Review • Cardiovascular • Complement-mediated Rare Disorders • Genetic Disorders • Hereditary Angioedema

Indirect treatment comparison of oral sebetralstat and intravenous recombinant human C1 esterase inhibitor for on-demand treatment of hereditary angioedema attacks. (PubMed, Allergy Asthma Clin Immunol) - P2/3, P3 | "This ITC found no significant differences in time to beginning of symptom relief and overall treatment-related treatment-emergent adverse events between sebetralstat and rhC1INH."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • STAT3

Targeting the Contact-Kinin System: A Cyclopeptide with Anti-Thromboinflammatory Properties Against Stroke. (PubMed, Eur J Pharmacol) - "The peptide also exerted comparable anti-ischemic stroke effects to those of ecallantide (DX-88), a kallikrein inhibitor approved for the treatment of hereditary angioedema, in a mouse model of transient middle cerebral artery occlusion. Thus, this short peptide CycloSD6, which dual targets FXII and PKa, harbors anti-thromboinflammation and anti-stroke properties with low bleeding risk. And these findings suggest that cycloSD6 may serve as a potential therapeutic candidate or template for the development of agents targeting ischemic stroke."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hereditary Angioedema • Infectious Disease • Inflammation • Influenza • Ischemic stroke • Respiratory Diseases • Thrombosis • IGH

A Case of Status Epilepticus in a Patient Experiencing an Acute Attack of Hereditary Angioedema. (PubMed, Clin Pract Cases Emerg Med) - "We present a case of status epilepticus in a patient with HAE-nl-C1-INH. The focus of emergent medical management of status epilepticus includes airway protection, respiratory support, and administration of abortive and prophylactic antiepileptic drugs. The emergency medicine physician should also consider and treat possible underlying etiologies. The treatment of an acute attack of HAE should focus on replacing C1-INH and preventing the formation and limiting the action of bradykinin."

Journal • Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Dermatology • Epilepsy • Genetic Disorders • Hereditary Angioedema • Immunology • Pruritus • Urticaria

Interplay between on-demand treatment trials for hereditary angioedema and treatment guidelines. (PubMed, J Allergy Clin Immunol) - "Pivotal trials for on-demand injectable treatments (plasma-derived C1 esterase inhibitor [C1INH], icatibant, ecallantide [US only], recombinant C1INH), which were approved in the US and EU between 2008-2014, were designed accordingly. This approach remains the cornerstone of current treatment guidelines and has shaped the design of recent clinical trials, such as those for the investigational agents, oral plasma kallikrein inhibitor sebetralstat and oral bradykinin B2 receptor antagonist deucrictibant. This narrative review discusses the evolution of on-demand treatment guidelines, the clinical trial and real-world data that prompted significant revisions, and the subsequent changes to trial designs introduced to facilitate guideline compliance."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

A mechanistic model of in vitro plasma activation to evaluate therapeutic kallikrein-kinin system inhibitors. (PubMed, PLoS Comput Biol) - "The present model represents a valuable framework for studying the intricate interactions within the plasma KKS and provides a better understanding of the mechanism of action of various KKS-targeted therapies."

Journal • Preclinical • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Hypertension • Inflammation

Perioperative Hereditary Angioedema Exacerbation Necessitating Diverse Management (ASA 2024) - "She was immediately given famotidine, diphenhydramine, and ecallantide which resolved her symptoms. Despite optimization, the stress of surgery and general anesthesia can be potential triggers of hereditary angioedema requiring aggressive medical management with different classes of medications."

Anesthesia • Cardiovascular • Complement-mediated Rare Disorders • Dysphonia • Gastrointestinal Disorder • Hereditary Angioedema

ACE – inhibitors induced angioedema (EUSEM 2024) - "A suspected angioedema after a pill of Ramipril...In the ICU angioedema specific treatment consisted of : hydrocortisone infusion, 1g of TXA i/v and 2 units of FFP...While some of the drugs as C1 inhibitor concentrate, ecallantide and icatibant are definitely unavailable in all the ED's. TXA and FFP might be helpful and should be easily reachable for many. TXA of 1 g is sufficient for most presenting with ACE – inhibitors induced angioedema and 2 units of FFP is the recommended dose for the adults.Having all this knowledge, facing a patient with a condition of ACE – inhibitors induced angioedema will not look that scary anymore."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Extension of the circulatory half-life of recombinant ecallantide via albumin fusion without loss of anti-kallikrein activity. (PubMed, J Biotechnol) - "HSA fusion decreases rEcall clearance in vivo, but LRP1-mediated clearance remains more important than FcRn-mediated recycling for rEcall fusion proteins. The properties of H6-rEcall-HSA warrant investigation in a murine model of HAE."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Dyslipidemia • Hereditary Angioedema • LRP1

Enhanced Long-Term Efficacy of an AAV8-DX88-HSA Vector for Treating Hereditary Angioedema (ASGCT 2024) - "In vitro and in vivo data demonstrated that AAV8-DX88-HSA robustly inhibited pKal activity. A single injection of the vector stably expressed DX88-HSA for at least 24 weeks in mice. These results support further development of expressing DX88 fusion protein mediated by AAV as a potential approach to treat HAE."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Gene Therapies • Hereditary Angioedema

Design, expression and biological evaluation of DX-88mut as a novel selective factor XIa inhibitor for antithrombosis. (PubMed, Bioorg Chem) - "Here, we designed the FXIa inhibitory peptide DX-88mut by replacing Loop1 (DGPCRAAHPR) and Loop2 (IYGGC) in DX-88, which is a clinical drug targeting PKa for the treatment of hereditary angioedema, using Loop1 (TGPCRAMISR) and Loop2 (FYGGC) in the FXIa inhibitory peptide PN2KPI, respectively...Additionally, DX-88mut did not show a significant bleeding risk at a dose of 5 µmol/kg. Taken together, these results show that DX-88mut is a potential candidate for the development of a novel antithrombotic agent."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hereditary Angioedema • Myocardial Infarction • Thrombosis • Venous Thromboembolism

Reasons Not To Treat HAE Attacks And Satisfaction For On-Demand Treatment (ACAAI 2023) - "76% of patients treated their most recent attack with icatibant (59.1%), pdC1-INH (26.9%), rhC1-INH (10.8%), or ecallantide (1.1%). Conclusion Physicians reported some patients reserve ODT for more severe attacks, despite the US HAEA Medical Advisory Board and WAO/EAACI recommendation that all attacks are considered for on-demand treatment. Physicians reported some dissatisfaction with the route of ODT administration and the ease of portability associated to it."

Pain

Pseudo-Allergies in the Emergency Department: A Common Misdiagnosis of Hypersensitivity Type 1 Allergic Reaction. (PubMed, Cureus) - "Histamine-mediated reactions, such as SFP, histamine-mediated angioedema, and mast cell degranulation induced by NSAIDs, and opioids can be treated with antihistamines, epinephrine, and corticosteroids. Bradykinin-induced angioedema, including hereditary angioedema and acquired angioedema, can be treated with fresh frozen plasma. Hereditary angioedema can be treated with many FDA-approved targeted medications, such as plasma-derived C1-INH, plasma kallikrein inhibitor (Ecallantide), and selective bradykinin-2 receptor antagonist (Icatibant). However, these targeted agents are not well-studied enough to be used for acquired angioedema. It is crucial for emergency medicine physicians to be familiar with and predict these reactions to prevent misdiagnosis, be prepared to treat these life-threatening conditions appropriately without delay and eliminate patients' exposure to any unnecessary investigations or treatments."

Journal • Review • Addiction (Opioid and Alcohol) • Allergy • Cardiovascular • Celiac Disease • Complement-mediated Rare Disorders • Eosinophilic Esophagitis • Gastrointestinal Disorder • Hereditary Angioedema • Immunology

"Management is awesome 1: icarubant 2: ecallantide @Sthanu5 @AaronGoodman33" (,@kumar_inguva34)

Specificity of contact pathway inhibitors with regard to other coagulation and fibrinolysis proteases. (ISTH 2023) - "CTI was very specific for factor XIIa with little inhibition of other factors (Figure). SBTI, ecallantide, and avoralstat were, as expected, very potent inhibitors of kallikrein. Avoralstat, at concentrations well above therapeutic levels, had weak inhibitory effect on many other coagulation enzymes."

Cardiovascular • Hematological Disorders • Thrombosis

Extending the Circulatory Half-life of an Engineered Kallikrein-Specific Inhibitor (ISTH 2023) - "Several drugs are licensed for HAE treatment and/or prophylaxis, including C1INH concentrates and recombinant Ecallantide (rEcall)... Fusion to HSA increased Ki values by 31% (Ki 2.9 ± 0.4 nM for H6-rEcall-HSA vs. 2.2 ± 0.1 nM for H6-rEcall, p = 0.008). 2h post-injection, 26 ± 2 % of H6-rEcall-HSA remained in circulation vs."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Study to Assess the Tolerability and Safety of Ecallantide in Children and Adolescents With Hereditary Angioedema (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: NYU Langone Health | N=10 ➔ 0 | Unknown status ➔ Withdrawn

Enrollment change • Trial withdrawal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Reporting of Adverse Drug Reactions with Parenteral Drugs for the On-Demand Treatment of Hereditary Angioedema Attacks – Analysis of the FAERS Database 2009 to 2022 (AAAAI 2023) - "This analysis suggests the real-world reporting rates of ADRs generally correspond to those included in the labels of parenteral HAE drugs. Significantly increased risk for hypersensitivity was found for ecallantide. Reporting rates of injection site reactions were significantly increased for pdC1-INH, and showed a trend for icatibant and rhC1-INH."

Adverse drug reaction • Cardiovascular • Complement-mediated Rare Disorders • Gastrointestinal Disorder • Hereditary Angioedema • Immunology • Pain

Safety of Medications for Hereditary Angioedema During Pregnancy and Lactation. (PubMed, Expert Opin Drug Saf) - "Additional research is needed to increase safe access to other therapy options. We are hoping that future clinical studies, registries, and databases will shed additional light on this subject."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema