Aygoren-Pursun E, Stobiecki M, Valerieva A, Cancian M, Gompels M, Grigoriadou S, Kiani-Alikhan S, Kinaciyan T, Yang WH, Anderson J, Arcoleo F, Chapdelaine H, Conlon N, Eren E, Guarino MD, Gurugama P, Magerl M, Manning ME, Tarzi MD, Wedner HJ, Zanichelli A, Crabbe R, Mulders S, Levy J, Zhu L, Knolle J, Lesage A, Lu P, Riedl MA

Apr/2026. The Lancet. Haematology

BACKGROUND: Hereditary angioedema is a bradykinin-mediated, rare condition characterised by recurrent and potentially life-threatening attacks of subcutaneous and submucosal swelling. Bradykinin B2 receptor antagonism is a proven mechanism for on-demand treatment of attacks, but no evidence exists on its effects when used prophylactically. Deucrictibant is an investigational orally bioavailable bradykinin B2 receptor antagonist. We aimed to evaluate the efficacy, safety, and tolerability of two dose regimens of oral deucrictibant administered as prophylaxis against hereditary angioedema attacks. METHODS: CHAPTER-1 was a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial conducted in two parts, a double-blind placebo controlled first part and an open-label second part, with only part 1 reported here. Part 1 recruited adults (aged 18-75 years) with hereditary angioedema type 1 or 2 from 37 sites (university hospitals and accredited angioedema centres) across North America, Europe, and Israel. Patients required a documented history of three or more attacks within the last 3 consecutive months before screening or two or more during the screening period (up to 8 weeks) to be eligible. An interactive response technology system randomised eligible patients 1:1:1 to receive oral deucrictibant 20 mg daily, 40 mg daily, or matching placebo for 12 weeks. Randomisation to treatment groups was stratified by the baseline attack rate. Patients, investigators, site personnel, and the sponsor were blinded to treatment assignment. Masking was achieved with identically appearing deucrictibant and placebo capsules. The primary endpoint was the time-normalised number of investigator-confirmed attacks per 4 weeks (monthly attack rate) from weeks 1 to 12 and was assessed using the intention-to-treat set. The endpoint was analysed by comparing each deucrictibant group with the placebo group using a Poisson generalised linear model with a log link function and Pearson's chi2 scaling of SEs to account for potential dispersion. The safety analysis set included all patients who were randomly assigned and who received one or more doses of study drug (deucrictibant or placebo). CHAPTER-1 is registered with ClinicalTrials.gov (NCT05047185) and is now complete. FINDINGS: Between March 9, 2022, and June 19, 2023, 44 patients were screened. Of 34 patients who were randomly assigned, 11 patients received deucrictibant 20 mg, 12 patients received deucrictibant 40 mg, and 11 patients received the placebo, with a median follow-up of 85.0 days (IQR 84.0-86.0). 21 (62%) patients were female, 13 (38%) were male, and 34 (100%) patients were White. The least squares mean monthly attack rate (primary analysis) was 0.40 (95% CI 0.18-0.92) for deucrictibant 20 mg, 0.30 (0.11-0.81) for deucrictibant 40 mg, and 1.93 (1.30-2.88) for placebo; percent reduction in attack rate compared with placebo was 79.2% (95% CI 47.2-91.8) for deucrictibant 20 mg (p=0.0010) and 84.5% (95% CI 53.8-94.8) for deucrictibant 40 mg (p=0.0008). Treatment-related treatment-emergent adverse events were experienced by two (18%) patients receiving deucrictibant 20 mg, one (8%) patient receiving deucrictibant 40 mg, and one (9%) patient receiving the placebo; all were mild in severity (grade 1) and did not require dosing modification of the study drug. There were no serious adverse events or deaths in any treatment group. INTERPRETATION: To the best of our knowledge, this trial provides the first clinical evidence and proof-of-concept for bradykinin B2 receptor antagonism as a therapeutic approach for the prevention of hereditary angioedema attacks and supports further investigation of oral deucrictibant for bradykinin-mediated angioedema. FUNDING: Pharvaris. Copyright The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

13(4):e215-e226

Available online at: https://dx.doi.org/10.1016/S2352-3026(26)00004-9

Busse PJ, Fok JS, Kamdar SS, Longhurst HJ, Riedl MA

Feb/2026. The journal of allergy and clinical immunology. In practice

Hereditary angioedema (HAE) with C1-inhibitor deficiency is a rare condition presenting with episodes of swelling without urticaria. Historically, acute and prophylactic HAE treatment options were limited and associated with considerable side effects, high burden of treatment, and unreliable symptom relief. Over the past decade, newer targeted therapies have been investigated and approved for both acute therapy and long-term prophylaxis. These therapies have dramatically reduced morbidity and mortality of HAE and consequently improved the quality of life of patients. This review article will outline the current and potential future treatments for HAE. Copyright © 2025 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

14(2):375-383

Available online at: https://dx.doi.org/10.1016/j.jaip.2025.11.039

Craig T, Aygoren-Pursun E, Bernstein JA, Busse PJ, Caballero T, Cohn DM, Guilarte M, Farkas H, Jones DH, Kiani-Alikhan S, Manning ME, Maurer M, Riedl MA, Savic S, Wedner HJ, Yong PFK, Zanichelli A, van Kooten S, Iverson M, Hansen E, Hao J, Smith MD, Yea CM, Audhya PK, Lumry WR

Mar/2026. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

BACKGROUND: People with hereditary angioedema (HAE) experience anxiety from the unpredictable nature of attacks and the burden of parenteral on-demand therapies, potentially leading to delays or avoidance of treatment. This analysis assessed factors associated with anxiety during attacks and the impact of oral sebetralstat versus placebo on anxiety in the KONFIDENT trial. METHODS: Participants in the randomised, double-blind, phase 3 KONFIDENT trial (NCT05259917) treated attacks with sebetralstat 300 mg, 600 mg or placebo as early as possible after onset. Anxiety was recorded at treatment administration, every 0.5 h thereafter through 4 h, hourly from 5 to 12 h and every 2 h from 14 to 24 h using an 11-point modified General Anxiety Numeric Rating Scale (GA-NRS). Prespecified exploratory endpoints assessed in all attacks and in attacks rated as inducing moderate-to-extreme anxiety (GA-NRS >= 4) included cumulative GA-NRS score and meaningful reduction in anxiety (defined as >= 2-point reduction in GA-NRS for >= 2 consecutive timepoints); least squares mean change from treatment administration in GA-NRS at 4 and 12 h was also assessed. This study was sponsored by KalVista Pharmaceuticals. RESULTS: Overall, 115 (44%) attacks were rated as inducing moderate-to-extreme anxiety. Female sex, shorter time since HAE diagnosis and greater attack severity were associated with greater anxiety at treatment administration. Reduction in cumulative anxiety after sebetralstat use was significantly greater versus placebo. The time to meaningful reduction in anxiety endpoint showed agreement with time to beginning of symptom relief, reduction in attack severity and complete attack resolution endpoints. CONCLUSION: Moderate-to-extreme anxiety was common in HAE attacks. Reduction in anxiety was significantly greater in attacks treated with sebetralstat compared with placebo. Copyright © 2026 KalVista Pharmaceuticals Inc and The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Available online at: https://dx.doi.org/10.1111/cea.70241

Davis-Lorton M, Soteres D, Lumry WR, Hall J, Connolly H, Fox D, Sing K, Schultz BG, Juethner S

Mar/2026. Allergy and asthma proceedings

Background: Hereditary angioedema (HAE) is a rare, potentially fatal genetic disorder characterized by unpredictable attacks of bodily swelling that substantially impair patients' quality of life (QoL). Lanadelumab is approved for long-term prophylaxis (LTP) in patients with HAE; however, there are limited real-world data that compare lanadelumab with other treatments to guide patient care. Objective: The objective was to describe real-world QoL and related outcomes of patients with HAE who received lanadelumab versus other LTP. Methods: Data were drawn from a real-world, cross-sectional survey of physicians and their consulting patients with HAE in the United States from January 2023 to January 2024. Physician-reported attack and disease severity, pain, fatigue, QoL, and patient-reported outcomes were compared among patients receiving lanadelumab or other LTP. Results: Physicians reported data on 86 patients treated with lanadelumab and 84 treated with other LTP. A statistically significantly higher proportion of patients receiving lanadelumab had no chronic pain (58.1%) and no chronic fatigue (51.2%) at the time of the survey than those receiving other LTP (38.1% [p = 0.0023] and 34.9% [p = 0.0037], respectively). More patients receiving lanadelumab had "very good" physician-reported QoL and less patient-reported QoL impairment at the time of the survey compared with those receiving other LTP (p = 0.0102). A higher proportion of patients receiving lanadelumab compared with other LTP reported complete satisfaction overall with their treatment (30.2% versus 17.9%, respectively; p = 0.0144) and complete satisfaction with the efficacy of their treatment (44.2% versus 11.9%, respectively; p < 0.0001). Conclusion: In this real-world study, physicians reported a higher proportion of patients receiving lanadelumab had no chronic pain or fatigue compared with those receiving other LTP. Both physicians and patients reported higher QoL in those receiving lanadelumab. Continued real-world research in patients with HAE to further assess the effect of lanadelumab on QoL will help guide patient care.

47(2):102-111

Available online at: https://dx.doi.org/10.2500/aap.2026.47.250104

Demidova A, Kiknavelidze N, Purtskhvanidze K, Alieva E, Ebrahimnejad M, Konchina S, Nurmeeva A, Matkovskii I, Elmurzaeva E, Davtian S, Degtyareva N, Drewitz KP, Asmanov A, Banjanin N, Botjes E, Comberiati P, Costa J, Chu DK, Epstein MM, Fedorova L, Galvin AD, Giovannini M, Greenhawt M, Jamalyan KR, Jones CJ, Khaleva E, Knibb RC, Leshem YA, Mack DP, Mafra I, Marchisotto MJ, Mijakoski D, Nurtazina A, Ozdemir C, Peroni D, Protudjer JLP, Del Rio PR, Schoos AM, Schopfer AF, Stoleski S, Upton J, van de Veen W, Genuneit J, Boyle RJ, Apfelbacher C, Munblit D

Apr/2026. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

BACKGROUND: Heterogeneity in outcome reporting and inconsistent use of outcome measurement instruments in allergy and clinical immunology research affects the comparability, synthesis, and clinical applicability of study findings. Harmonisation efforts, particularly Core Outcome Set (COS) development, aim to address these challenges by establishing standardised, evidence-based and consensus-driven outcome recommendations. This systematic review aims to map available COS and other harmonisation processes (HP) in allergy and clinical immunology, evaluate their methodological approaches, and assess their alignment with established development standards. METHODS: We systematically searched MEDLINE, EMBASE, and the COMET Initiative database until June 7, 2024 to identify COS and HP. We included studies if they provided recommendations on 'core' outcomes and/or outcome measurement instruments. Data extraction included disease focus, methodological approach, stakeholder involvement, and adherence to the Core Outcome Set-STAndards for Development criteria. We synthesised the data at the initiative (process) level rather than the publication level because harmonisation initiatives are frequently iterative and reported across multiple papers (e.g., protocol, Delphi rounds, consensus statement, and subsequent instrument-selection outputs). RESULTS: A total of 15,612 records were identified, with 44 studies (representing 22 initiatives both finished and in development) meeting inclusion criteria. The majority of initiatives focused on asthma (n = 9), followed by eczema (atopic dermatitis n = 2; hand eczema = 1; eczema = 1), urticaria (n = 2), allergic rhinitis (n = 2), chronic rhinosinusitis (n = 1), celiac disease (n = 1), Immunoglobulin E (IgE)-mediated food allergy (n = 1), eosinophilic esophagitis (n = 1), and hereditary angioedema (n = 1). No COS or HP addressed drug allergy, anaphylaxis, or other immune-mediated allergic conditions. 'Quality of life' was consistently included in all COS with 'signs and symptoms', 'exacerbations' and 'disease control' frequently selected as well. Methodological approaches to COS development varied widely, with most employing Delphi surveys, consensus meetings, and stakeholder involvement, though levels of engagement differed. COS developers inconsistently adhered to Core Outcome Set-STAndards for Development criteria, with some initiatives demonstrating rigorous methodology while others lacked transparency in key developmental steps. CONCLUSION: This review highlights growing efforts to harmonise outcome assessment in allergy and clinical immunology. Major gaps remain in coverage and methodological rigour. Quality of life and patient-reported symptoms are frequently recommended outcomes, yet definitions and measurement tools are inconsistent. Strengthening methodological consistency and expanding COS development to neglected areas are critical next steps to improve outcome reliability and comparability in the field. Copyright © 2026 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Available online at: https://dx.doi.org/10.1111/cea.70251

Diep JK, Liu M, Singh P, Dorow S, Cohn DM, Bordone L, Newman KB, Gao X

Feb/2026. CPT: pharmacometrics & systems pharmacology

Hereditary angioedema (HAE) is a rare disorder linked to kallikrein-kinin system dysregulation, which leads to uncontrolled activation of plasma prekallikrein. Donidalorsen is an antisense oligonucleotide designed to selectively degrade prekallikrein messenger RNA and thereby reduce prekallikrein production. We aimed to develop population pharmacokinetic and pharmacokinetic/pharmacodynamic models of donidalorsen and evaluate the impact of potential intrinsic/extrinsic covariates on exposure and prekallikrein response. Plasma donidalorsen and prekallikrein data were obtained from phase 1 to 3 studies in healthy volunteers (NCT03263507, 721744-CS9) and adult and adolescent patients with HAE (NCT04030598, NCT05139810). The evaluated doses were 20, 40, 60, and 80 mg every 4 weeks (Q4W) and 80 mg every 8 weeks (Q8W), administered subcutaneously over 13-21 weeks. Donidalorsen pharmacokinetics were well described by a linear 2-compartment model with first-order absorption. The population terminal elimination half-life was 31.4 days. Prekallikrein was well described by an indirect response model with inhibition of prekallikrein production by donidalorsen. Covariate analysis identified body weight as the main factor affecting pharmacokinetic exposure; however, this effect was not considered clinically significant. The developed population pharmacokinetic/pharmacodynamic model well characterized the donidalorsen exposure-prekallikrein response relationship. Modeling analyses support that no dose adjustment is needed with respect to intrinsic/extrinsic factors in adults and adolescents with HAE. The nearly identical simulated pharmacokinetic or prekallikrein time courses for Q4W versus monthly dosing and for Q8W versus every-2-month dosing regimens support switching to more convenient regimens for patients. Copyright © 2026 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

15(2):e70206

Available online at: https://dx.doi.org/10.1002/psp4.70206

Glassman F, Lawo JP, Bica MA, Roberts A, Kormann D, Chialda L, Miethke S, Dziadowiec I, Caltabiano S, Puchalski T

Jan/2026. Journal of clinical pharmacology

Garadacimab is a novel, fully human, anti-activated factor XII monoclonal antibody approved for long-term prophylaxis of patients with hereditary angioedema. This open-label, parallel-group, Phase 1, single-center, bridging study in healthy adults (18-55 years of age) characterized the pharmacokinetics and safety of a single 200 mg subcutaneous injection of garadacimab administered via autoinjector/pre-filled pen (AI/PFP) compared with the pre-filled syringe (PFS) used in previous studies. The aim of the study was to bridge the understanding of the PK and safety of garadacimab between PFS and AI/PFP modes of administration. Participants (N = 132) were stratified by body weight, randomized evenly in six groups by device (AI/PFP or PFS) and injection site (abdomen, thigh, or upper arm). The primary endpoint comprised pharmacokinetic parameter comparison between devices. Safety/tolerability were secondary endpoints. The geometric mean ratio (GMR) for Cmax and AUC0-inf comparing administration by PFS and AI/PFP was close to 1 with 90% confidence intervals within a range of 0.8-1.25, meeting bioequivalence criteria; GMR (90%) was 0.92 (0.81, 1.05) for Cmax and 0.96 (0.87, 1.07) for AUC0-inf. No participants in this study had anti-drug antibodies against garadacimab. Treatment-related emergent adverse events were reported in 9/66 (13.6%) participants in the PFS group and 11/66 (16.7%) participants in the AI/PFP group. Garadacimab 200 mg administered as a single subcutaneous dose via AI/PFP had a consistent safety and tolerability profile to that administered via PFS. These findings support administration of garadacimab via AI/PFP, providing at-home convenience for patients and physicians. Copyright © 2025 The Author(s). The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.

66(1):e70099

Available online at: https://dx.doi.org/10.1002/jcph.70099

Hollers E, Yu Y, Sheetz J, Richwine K, Grim K, Germak-Sovereign R, Luong L, Hitomi H, Al-Shaikhly T, Craig T

Mar/2026. The World Allergy Organization journal

Introduction: Hereditary angioedema (HAE) types 1 and 2 are caused by C1 inhibitor deficiency or dysfunction, leading to increased prekallikrein activity and bradykinin production. HAE causes vasodilation and edema resulting in obstruction of the upper airway, gastrointestinal symptoms, and skin swelling. Evidence of involvement of other organ systems has been sparse. Herein, we demonstrate evidence of creatinine kinase (CK) elevation in HAE patients suggesting an effect of bradykinin on skeletal muscle with subsequent improvement with long term prophylaxis (LTP). Methods: CK levels from participants with type 1 or 2 HAE enrolled in the Phase 2 and 3 clinical trials evaluating the safety and efficacy of donidalorsen for LTP in patients with HAE, was measured at baseline (before treatment initiation) and Week 17 (for participants enrolled in Phase 2 Study) and Week 25 (for participants enrolled in Phase 3 study). Mixed effect model with repeated measures was used to assess the influence of time and treatment (donidalorsen vs. placebo) on serum CK levels. Results: CK levels were available from 20 patients enrolled in the Phase 2 study and the mean CK level was numerically lower by Week 17; however, these results were not statistically significant. Among the 90 participants enrolled in the Phase 3 study who had CK levels checked at baseline and Week 25, a significantly lower CK level at Week 25 was observed among those receiving Q4W donidalorsen, but not among those receiving donidalorsen Q8W or placebo. Conclusion: Bradykinin appears to cause instability of skeletal muscle, causing CK release with even minor exercise. The effect of increases in bradykinin in HAE on muscle needs further research but may account for some of the atypical HAE symptoms patients often describe and which are noted in quality-of-life assessments. LTP, therefore, may confer additional benefits beyond reduction of HAE symptoms, potentially contributing to stabilization of skeletal muscle and improvement of fatigue and weakness. Copyright © 2026 The Authors.

19(3):101350

Available online at: https://dx.doi.org/10.1016/j.waojou.2026.101350

Levrini L, Saran S, Imbesi E, Vanini I, Russo V, Rimoldi V, Carganico A, Giannotta N, Perugini M

Mar/2026. Frontiers in dental medicine

Introduction: Maxillary transverse deficiency (MTD) is a common craniofacial condition associated with posterior crossbite, dental crowding, and compromised respiratory function. This study aimed to evaluate whether the Invisalign Palatal Expander (IPE) can induce midpalatal suture opening and occlusal changes, and to compare these outcomes with those obtained using conventional rapid palatal expansion (RPE). Materials and methods: Thirty subjects (14 females, 16 males; aged 6-18 years) with mixed dentition were enrolled and divided into two groups: 15 treated with IPE and 15 with RPE. Radiographic images and digital dental models were analyzed before (T0) and after treatment (T1) to assess skeletal and occlusal changes, including midpalatal suture opening and transverse arch dimensions. Molar tipping and palatal depth were also measured. Patient-reported side effects during the first month of treatment were evaluated using a questionnaire addressing bulkiness, tongue impression, dysphonia, dysphagia, and gag reflex, scored on a 1-5 scale. Inclusion criteria comprised mixed dentition, erupted first molars, deciduous fourth/fifth teeth or erupting premolars, and complete diagnostic records. Exclusion criteria included previous orthodontic treatment, craniofacial anomalies, extraction therapy, allergies, hereditary angioedema, or active caries. Results: No significant differences were found between groups in the number of activations, radiographic outcomes, or theoretical expansion, indicating comparable skeletal effects. Midpalatal suture opening was achieved in all patients. Baseline occlusal conditions were similar between groups. After normalization for the number of activations, statistically significant differences were observed for arch depth, canine gingival width, canine dental width, and arch perimeter, all of which were greater in the RPE group (p < 0.05). No significant differences were found in intermolar angle or palatal depth changes. Questionnaire analysis revealed no significant differences in reported side effects between groups. Conclusions: The Invisalign Palatal Expander effectively produced transverse maxillary expansion with midpalatal suture opening, yielding skeletal and occlusal outcomes comparable to those of the Hyrax expander. Although the amount of expansion was slightly lower, the IPE demonstrated more controlled and predictable results, supporting its use as a valid alternative in mixed dentition and as a step toward fully digital orthodontic protocols. Copyright © 2026 Levrini, Saran, Imbesi, Vanini, Russo, Rimoldi, Carganico, Giannotta and Perugini.

7:1757094

Available online at: https://dx.doi.org/10.3389/fdmed.2026.1757094

Lobao NTM, Bardou MLD, Vila SYC, Sousa Ferreira LS, Arruda LK, Lemos JES, Ferriani MPL, Dias MM, Toledo EC, Serpa FS, Moyses TR, Chong-Neto HJ, Rosario Filho NA, de Moraes CGFB, Marcelino FC, Mansour E, Coutinho CRE, Mendes RC, Goncalves RF, Valle SOR, Oliva-Alonso ML, Dortas Junior SD, da Silva J, de Souza ALF, Ensina LF, Morato V, de Albuquerque Campos R, Pesquero JB, Constantino-Silva RN, Grumach AS

Jan/2026. The journal of allergy and clinical immunology. In practice

BACKGROUND: Hereditary angioedema (HAE) with normal C1 inhibitor (HAE-nC1INH) is a rare and heterogeneous group of bradykinin-mediated disorders, characterized by diagnostic challenges and limited evidence-based recommendations. OBJECTIVE: To describe the clinical features and therapeutic strategies of Brazilian patients with HAE-nC1INH, supporting individualized, subtype-oriented management. METHODS: This multicenter, cross-sectional analytical study was conducted through the Brazilian Group for the Study of Hereditary Angioedema (GEBRAEH). Data were collected in December 2024 using a standardized online questionnaire and analyzed descriptively and inferentially. RESULTS: A total of 116 symptomatic patients were included: 92 with HAE with mutation in coagulation factor XII, 21 with HAE of unknown genetic cause, and 3 with HAE with mutation in angiopoietin-1. Females accounted for 96%. Abdominal symptoms were predominant, and diagnostic delay decreased in more recent generations. Initial interventions most often involved isolated combined estrogen-progestin oral contraceptive (COC) withdrawal (33 of 116; 28%) or combined with progestins (35 of 116; 30%). In HAE with mutation in coagulation factor XII, COC withdrawal was effective in 97% (29 of 30), further enhanced with progestins (30 of 30; 100%). COC withdrawal reduced median attack days (4.5 to 1; P < .001) and prolonged attack-free intervals (P < .001). Four patients relapsed after more than 10 years of remission, associated with hormonal changes. Tranexamic acid demonstrated variable efficacy (2 of 10 achieved complete cessation, 5 of 10 partial reduction, and 3 of 10 no response). Lanadelumab showed clinical efficacy in HAE of unknown genetic cause (2 of 2) and HAE with mutation in angiopoietin-1 (1 of 1). Androgens showed only limited benefit (7 of 7; all partial reduction). CONCLUSIONS: COC withdrawal is the most effective first-line intervention in HAE with mutation in coagulation factor XII, with greater efficacy when combined with progestins. Tranexamic acid and lanadelumab may serve as complementary options in selected cases. Late relapse highlights the need for long-term follow-up, with intensified monitoring during periods of hormonal fluctuation. Copyright © 2025 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

14(1):233-242.e2

Available online at: https://dx.doi.org/10.1016/j.jaip.2025.10.001

Lumry WR, Davis-Lorton M, Soteres D, Earl L, Wynne-Cattanach K, Fox D, Sing K, Juethner S, Schultz BG

Jul/2026. International archives of allergy and immunology

Introduction: Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, painful swelling attacks that significantly impair patients' quality of life (QoL). Clinical trials of lanadelumab led to its approval for long-term prophylaxis in patients with HAE; however, real-world data on long-term lanadelumab use in patients with HAE are limited. This analysis describes real-world outcomes of patients with HAE who have received lanadelumab as long-term prophylaxis for >=3 years. METHODS: From January 2023 to January 2024, investigators collected data from the Adelphi Wave II Disease Specific Programme TM, a real-world, cross-sectional survey of physicians and their patients with HAE in the USA. Physicians retrospectively reported attack frequency, attack severity, and QoL before lanadelumab initiation, at 12, 24, and 36 months post initiation, and at the time of the survey. RESULTS: Physicians reported data on 51 patients who had received lanadelumab for >=3 years. Before lanadelumab initiation, physicians reported attack severity as mild in 49.0% of patients and very severe in 8.2%; at 36 months post lanadelumab initiation, 62.5% of patients experienced mild attacks and none experienced very severe attacks in the preceding year. The proportion of patients experiencing >=1 attack per month on average decreased from 54.0% before lanadelumab initiation to 9.8% at the time of the survey. The proportion of patients with good or excellent QoL increased from 68.6% before lanadelumab initiation to 88.2% at the time of the survey. CONCLUSION: In this real-world HAE study, patients treated with lanadelumab for >=3 years experienced improvements in attack frequency, disease severity, and QoL. . Copyright © 2025 The Author(s). Published by S. Karger AG, Basel.

187(3):289-298

Available online at: https://dx.doi.org/10.1159/000546987

Lumry WR, Tachdjian R, Craig T, Karakaya G, Gelincik A, Stobiecki M, Jacobs JS, Gokmen NM, Reshef A, Manning ME, Grammatikos A, Giardino F, Guilarte M, Baptist AP, Bordone L, Newman KB, Treadwell S, Lin T, Yarlas A, Riedl MA, Cohn DM.

Feb/2026. Journal of asthma and allergy

Background: Donidalorsen, a prekallikrein-directed antisense oligonucleotide indicated for prophylaxis of hereditary angioedema (HAE) attacks in patients aged >=12 years, demonstrated efficacy and acceptable safety in the phase 3, placebo-controlled OASIS-HAE trial (NCT05139810). Here, we report 1-year results from the corresponding open-label extension (OLE) cohort of the OASISplus study (NCT05392114). Methods: OASISplus included patients who rolled over from OASIS-HAE. Patients who received donidalorsen 80 mg or placebo subcutaneously every 4 weeks (Q4W) in OASIS-HAE received donidalorsen Q4W in OASISplus. Patients who received donidalorsen 80 mg or placebo every 8 weeks (Q8W) in OASIS-HAE received donidalorsen Q8W or Q4W, if not attack-free in the final 8 weeks of OASIS-HAE. The primary endpoint was safety (ie, incidence of treatment-emergent adverse events [TEAEs]). Secondary endpoints included the monthly rate of HAE attacks and Angioedema Quality of Life (AE-QoL). Results: The OLE cohort included 83 patients (Q4W, n=69 [83%]; Q8W, n=14 [17%]). Of these, 75 (90.4%) completed Year 1, and 6 patients receiving donidalorsen Q8W in OASIS-HAE switched to the Q4W dosing group in the OLE. Median donidalorsen exposure was 392.3 days. From Weeks 0 to 52, reductions in mean HAE attack rate from OASIS-HAE baseline were 94% (Q4W) and 95% (Q8W), and patients reported clinically meaningful improvements in mean AE-QoL total score at Week 52 (Q4W, 28.1 points; Q8W, 26.7 points). Twenty-two (27%) patients reported treatment-related TEAEs; none were serious, and injection-site reactions were the most frequently reported. Conclusion: Donidalorsen demonstrated sustained reductions in HAE attack rate, improvements in QoL, and an acceptable safety profile after 1 year of treatment. Copyright © 2026 Lumry et al.

19:592079

Available online at: https://dx.doi.org/10.2147/JAA.S592079

Maurer M, Stobiecki M, Valerieva A, Hakl R, Staevska MT, Bouillet L, Du-Thanh A, Kessel A, Kiani-Alikhan S, Magerl M, Reshef A, Baeza ML, Fain O, Farkas H, Greve J, Guilarte M, Jacobs JS, Li HH, Lleonart R, Manning ME, Sussman GL, Anderson J, Chapdelaine H, Cohn DM, Hagin D, Kralickova P, Ritchie B, Spadaro G, Staubach P, Tarzi MD, Yang WH, Jouvin MH, Crabbe R, van Leeuwen S, Chen H, Zhu L, Knolle J, Lesage A, Lu P, Riedl MA, Aygoren-Pursun E

Apr/2026. The Lancet. Haematology

BACKGROUND: Hereditary angioedema is a bradykinin-mediated disorder characterised by recurrent painful swelling attacks. Treatment relies on medications to prevent attacks and on-demand therapies for attack manifestations. Parenteral administration associated with most available on-demand therapies often leads to treatment being delayed or forgone. Deucrictibant is an orally bioavailable bradykinin B2 receptor antagonist under development for prophylaxis and on-demand treatment of hereditary angioedema attacks. We aimed to investigate the efficacy and safety of deucrictibant for the on-demand treatment of hereditary angioedema attacks. METHODS: RAPIDe-1 was a double-blind, randomised, placebo-controlled, crossover, dose-ranging, phase 2 trial that recruited adults aged 18-75 years with hereditary angioedema type 1 or 2 from 38 sites (eg, university hospitals and accredited angioedema centres) across North America, Europe, and Israel. Participants were required to have experienced two or more attacks within the past 2 months or three or more attacks within the past 4 months before screening. An interactive response technology system randomly assigned eligible patients (1:1:1) to receive a blinded dose of oral deucrictibant (immediate-release capsule) 10 mg, 20 mg, or 30 mg during an attack-free period to assess pharmacokinetics and safety in the part 1 of the study; and, subsequently, to receive a crossover treatment sequence of two administrations of the same deucrictibant dose (10 mg, 20 mg, or 30 mg) and one of placebo to treat three investigator-confirmed angioedema attacks in the part 2. Randomisation was stratified by whether the participant was willing to participate in full pharmacokinetic sampling. Participants , investigators, site personnel, and the sponsor were masked to treatment assignment and capsules of deucrictibant and placebo were identical. For each attack, patients self-administered the oral study drug within 3 h after at least one symptom (skin pain, skin swelling, or abdominal pain) reached a visual analog scale (VAS) individual score of 30 or more out of 100 and within 6 h from symptom onset. The primary endpoint was change in the patient-reported composite VAS-3 score measuring severity of attack manifestations from before treatment to 4 h post-treatment and assessed in the modified intention-to-treat and per-protocol populations. Safety was assessed in all patients who received any dose of study drug. RAPIDe-1 is registered with ClinicalTrials.gov (NCT04618211) and is completed. FINDINGS: Between Feb 3, 2021, and June 23, 2022, 89 patients were screened, of whom 74 were randomly assigned between Feb 23, 2021, and July 26, 2022. For the primary analysis set, the median follow-up was 130.0 (IQR 92.5 to 212.5) days for the deucrictibant 10 mg group, 166.5 (80.0 to 275.0) days for the deucrictibant 20 mg group, and 172.0 (65.0 to 242.0) days for the deucrictibant 30 mg group. The primary efficacy analysis included 147 attacks in 62 patients, of whom 42 (68%) were female and 60 (97%) were White. Least squares mean differences of change in VAS-3 score between deucrictibant and placebo was -16.75 (95% CI -21.52 to -11.97) for 10 mg, -15.02 (-20.22 to -9.81; p<0.0001) for 20 mg, and -16.28 (-21.27 to -11.29; p<0.0001) for 30 mg. In part 1, all treatment-emergent adverse events were grades 1-2, with the most common in two or more patients being headache (two [8%] of 25) and nasopharyngitis (two [8%] of 25) in the deucrictibant 30 mg group. In part 2, no single treatment-emergent adverse event was reported by two or more patients in any treatment group. Most adverse events were considered unrelated to the study drug and there were no grade 3 or worse adverse events. INTERPRETATION: Deucrictibant significantly reduced the severity of hereditary angioedema attacks compared with placebo; these results support continued investigation of antagonism of the bradykinin B2 receptor with an orally available agent as a potentially effective approach, with a safety profile similar to placebo, for on-demand treatment. FUNDING: Pharvaris. Copyright © 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

13(4):e200-e214

Available online at: https://dx.doi.org/10.1016/S2352-3026(25)00341-2

Olson C, Lionetti M, Poulos C, Ray T, Lopez-Gonzalez L, Nestler-Parr S, Gillard P, Soteres D

Mar/2026. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

BACKGROUND: Long-term prophylaxis (LTP) can help manage hereditary angioedema (HAE). With increasing LTP treatment options, understanding patients' preferences is important for shared decision-making. OBJECTIVE: To understand the way individuals with HAE assess the importance of LTP treatment attributes, their LTP treatment preferences, and the impact of disease and treatment attributes on their willingness to switch LTP. METHODS: We conducted an online survey in 2023 among US adults (aged >=18 years) self-reporting an HAE diagnosis and receiving treatment (LTP, on-demand, or both) or experiencing at least 1 attack in the past 3 months. Best-worst scaling and a discrete choice experiment assessed LTP preferences. A behavior change model assessed willingness to switch LTP. RESULTS: A total of 150 individuals completed the survey. Respondents rated effectiveness in preventing attacks and reducing the severity of attacks as the most important LTP attributes. Route of administration and convenience were more than twice as important as dosing frequency. Individuals preferred oral daily therapy to biweekly (54% vs 46%) or monthly injections (54% vs 46%). Most individuals (71%) were at least somewhat willing to switch LTP treatments in the next 6 months, particularly those whose HAE was not well controlled, were anxious about taking LTP, were burdened by treating their HAE, or preferred oral administration. CONCLUSION: Effectiveness was the primary driver of LTP preference; other factors were also important, including convenience. When effectiveness was equivalent, oral administration was preferred to injectable administration. Individuals with HAE were moderately willing to switch their LTP. By better understanding patients' treatment preferences, health care professionals can individualize LTP recommendations. Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.

136(3):322-332

Available online at: https://dx.doi.org/10.1016/j.anai.2025.12.011

Sahli A, C-Gaudreault R, Marceau F

Jan/2026. Peptides

Bradykinin is a nonapeptide derived from the cleavage of circulating kininogens by plasma or tissue kallikreins and is endowed with powerful pharmacologic actions, such as the production of protein-rich exudates and vasodilation. The widely expressed B2 receptor for bradykinin (a G protein-coupled receptor) has been the focus of intense drug development efforts for more than 4 decades, with marked differences in affinities and competitiveness for synthetic antagonists across mammalian species. Many non-peptide ligands of the human B2 receptor have been developed by various industrial organizations. A recurring substituted 8-[(2,6-dichlorophenyl)methoxy]-2-methylquinolinyl ("quinolyl") moiety, or variants thereof, was explored by several pharmaceutical organizations. FR173657, fasitibant, anatibant, deucrictibant and Compound 3 (the non-deuterated version of deucrictibant) are examples of competitive antagonists of the human B2 receptor, some of which having reached the stage of clinical trials. Other compounds structurally related to the common moiety, such as FR190997 and Compound 47a, are partial or nearly full agonists of the B2 receptor. The ongoing clinical development of deucrictibant for the treatment of hereditary angioedema is a first step in clarifying the therapeutic potential of orally bioavailable B2 receptor antagonists. Copyright © 2026 Elsevier Inc. All rights reserved.

195:171466

Available online at: https://dx.doi.org/10.1016/j.peptides.2026.171466

Sundler Bjorkman L, Eswaran H, Grover SP

Feb/2026. Arteriosclerosis, thrombosis, and vascular biology

C1INH (C1-inhibitor) is a multifunctional SERPIN (serine protease inhibitor) that functions as a major negative regulator of the complement, coagulation, and kallikrein-kinin systems. C1INH products were originally developed for the treatment of hereditary angioedema associated with C1INH deficiency. A growing body of literature indicates that C1INH products may find utility in the management of several other disease states. In this review, we detail the key biological activities of C1INH and consider the pathophysiological role of C1INH targets in many conditions. The therapeutic potential of exogenous C1INH is highlighted in the settings of thromboembolism, ischemia-reperfusion injury, sepsis, transplantation, and coronavirus disease 2019.

46(2):e323743

Available online at: https://dx.doi.org/10.1161/ATVBAHA.125.323743

Syed YY

Feb/2026. Drugs

Donidalorsen (DAWNZERA TM) is a first-in-class, RNA-targeted antisense oligonucleotide (ASO), developed by Ionis Pharmaceuticals for the prevention of hereditary angioedema (HAE) attacks. It received its first approval on 21 August 2025 in the USA for the prophylaxis of HAE attacks in adult and paediatric patients aged 12 years and older. Donidalorsen is currently under regulatory review in the EU and in phase III development in several other countries. This article summarizes the key milestones in the development of donidalorsen leading to its first approval for HAE. Copyright © 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

86(2):243-248

Available online at: https://dx.doi.org/10.1007/s40265-025-02257-y

Yarlas A, Feld AJ, Bjorner JB, Thurm C, Bordone L, Newman KB, Treadwell S, Cohn DM

Jan/2026. Clinical and translational allergy

BACKGROUND: Hereditary angioedema (HAE), defined by unpredictable, painful, acute swelling attacks affecting several bodily locations, diminishes patients' quality of life. Assessing disease activity, burden, and treatment response pose challenges in routine care. The patient-reported Angioedema Control Test (AECT) is a subjective measure of HAE disease control. Criterion validity of AECT with objective measures of disease control has not been previously assessed. This study evaluates the criterion validity of AECT using investigator-confirmed HAE attack rate in patients with HAE. METHODS: The Phase 3 OASIS-HAE study (NCT05139810) randomized patients with HAE to receive donidalorsen 80 mg or placebo subcutaneously for 24 weeks. The full analysis population included all dosed patients (N = 90), pooled across treatment arms. This post-hoc analysis examined the correlation between AECT and HAE attacks at Baseline, 12, and 24 weeks. RESULTS: AECT scores correlated moderately to strongly with HAE attack rate (rho = -0.40 to -0.85). Mean attack rates differed significantly between poor (AECT < 10) and well-controlled (AECT >= 10) disease subgroups at study visits. At Week 24, 97.4% of patients reporting complete disease control (AECT maximum score of 16) had an attack rate of 0; the remaining patient had 1 attack. Patients with no attacks had a mean AECT score of 15.1 versus 7.7 for patients with attack rates > 0. CONCLUSION: This study supports the criterion validity of AECT in patients with HAE scores. AECT scores were strongly associated with objective disease control. AECT may be a valuable tool for monitoring disease control in patients with HAE. Copyright © 2026 Ionis Pharmaceuticals, Inc. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.

16(1):e70143

Available online at: https://dx.doi.org/10.1002/clt2.70143