Spotlight on hereditary angioedema: Clinical trial highlights from EAACI 2026

EAACI 2026 showcased advances in gene editing, oral therapies and long-acting prophylaxis for hereditary angioedema.

New clinical data presented at EAACI Congress 2026 highlighted the continued evolution of hereditary angioedema (HAE) management. Alongside established long-term prophylactic and on-demand treatment strategies, investigational therapies are aiming to reduce treatment burden through oral formulations, longer dosing intervals and, potentially, one-time disease-modifying approaches.

Here, we summarise some of the key HAE clinical trial updates presented at this year’s meeting.

touchIMMUNOLOGY coverage of EAACI 2026

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Gene editing moves closer to clinical practice

Lonvoguran ziclumeran: Positive Phase 3 HAELO results

The phase 3 HAELO study (NCT06634420) evaluated lonvoguran ziclumeran (lonvo-z; NTLA-2002), an investigational in vivo CRISPR-based gene-editing therapy, as a one-time treatment for HAE due to C1 Esterase Inhibitor deficiency.

Primary analyses showed that between Weeks 5 and 28, lonvo-z reduced the mean monthly HAE attack rate by 87% compared with placebo (0.26 vs 2.10 attacks/month, respectively; p <0.0001). Significant reductions were also reported in attacks requiring on-demand treatment, 0.19 with lonvo-z vs 1.79 with placebo (p <0.0001), and moderate-to-severe attacks, 0.11 with lonvo-z vs 1.23 with placebo (p <0.0001). Furthermore, 62% of treated patients remained attack-free from Week 5–28 compared with 11% of those receiving placebo. Improvements in quality of life were also observed.

Lonvoguran ziclumeran was generally well tolerated, with infusion-related reactions being the most common adverse event and no serious or Grade 3 treatment-related adverse events (TRAEs) reported. Longer-term follow-up will determine the durability of this one-time gene-editing approach.

Abstract: HAELO, a Phase 3, Global, Randomised, Double-Blind, Placebo-Controlled Study of Lonvoguran Ziclumeran, a CRISPR-Based Gene Editing Therapy, in Patients with Hereditary Angioedema.

Oral therapies continue to expand treatment options

Deucrictibant: Phase 3 RAPIDe-3 meets key endpoints

Several presentations focused on deucrictibant, an oral bradykinin B2 receptor antagonist under investigation for both on-demand treatment and long-term prophylaxis.

Results from the phase 3 RAPIDe-3 trial (NCT06343779) showed significantly faster symptom relief with deucrictibant compared to placebo. Median time to onset of symptom relief was 1.28 hours with deucrictibant versus >12 hours with placebo (p <0.0001), with median time to substantial symptom relief also significantly reduced with deucrictibant versus placebo (2.85 hours versus >12 hours, respectively; p <0.0001). Complete resolution occurred in a median of 11.95 hours with deucrictibant versus >48 hours with placebo (p <0.0001).

A second RAPIDe-3 analysis examined end of progression, a measure of when attacks stop worsening. Median time to end of progression was 17.47 minutes with deucrictibant compared with 228.67 minutes for placebo (p <0.0001), with 92.8% of treated attacks reaching this endpoint within 12 hours in the deucrictibant-treated arm versus 60.9% with placebo.

Deucrictibant demonstrated a favourable safety profile, with no serious treatment-related adverse events reported.

Abstracts:

• Oral Deucrictibant Immediate-Release Capsule for On-Demand Treatment of Hereditary Angioedema Attacks: Results of the Phase 3 RAPIDe-3 Trial.
• Oral Deucrictibant Immediate-Release Capsule for On-Demand Treatment of Hereditary Angioedema Attacks: End of Progression Results in the Phase 3 RAPIDe-3 Trial.

Deucrictibant: Durable prophylactic efficacy

Long-term results from the CHAPTER-1 open-label extension study (NCT05047185) supported the continued evaluation of deucrictibant as a prophylactic therapy. During the OLE, monthly attack rate remained low at 0.12, irrespective of baseline disease activity, while rates of moderate-to-severe attacks and attacks requiring on-demand treatment remained minimal.

No serious treatment-emergent adverse events (TEAEs) or TEAEs causing discontinuation were reported during the extension, providing further evidence for the long-term safety and efficacy of daily oral prophylaxis.

Abstract: Results of the Phase 2 CHAPTER-1 Open-Label Extension Study on the Long-Term Safety and Efficacy of Oral Deucrictibant for Prophylaxis in Hereditary Angioedema.

Sebetralstat: Oral short-term prophylaxis explored

Preliminary data from the ongoing KONFIDENT-S open-label extension (NCT05505916) evaluated oral sebetralstat, a plasma kallikrein inhibitor, as short-term prophylaxis before medical, surgical, or dental procedures. Currently, sebetralstat is widely approved as the first oral on-demand therapy for HAE attacks.

Among participants who received at least two prophylactic doses, the attack rate within 24 hours of a procedure was 2.3%, with no attacks reported following completion of the full three-dose regimen. Although these findings are based on a small number of procedures, they support further evaluation of sebetralstat as an oral alternative to intravenous short-term prophylaxis.

Abstract: Use of Sebetralstat as Short-term Prophylaxis for Patients with Hereditary Angioedema: Results from the KONFIDENT-S Study.

Berotralstat: Paediatric data support long-term use

The ongoing APeX-P open-label study (NCT05453968) is evaluating berotralstat, an oral small-molecule plasma kallikrein inhibitor, in patients with HAE aged 2 to <12. Berotralstat is already approved as a long-term prophylactic in children aged 2 to <12 years in the US.

Updated 48-week findings demonstrated following treatment initiation, attacks requiring on-demand medication decreased from a median of 0.691 to 0.169 attacks per month, while the number of attacks requiring professional medical care also declined.

Berotralstat continued to demonstrate a favourable safety profile, with no drug-related serious adverse events or AE-related treatment discontinuations reported through 48 weeks. The most common TEAEs were nasopharyngitis, upper respiratory tract infection, and vomiting.

Abstract: Berotralstat Decreased HAE Attacks Treated with On-Demand Therapy or Utilizing Professional Care in Pediatric Patients Aged 2 to <12 years: APeX-P Results Through 48 Weeks.

Longer-acting prophylaxis remains a major area of innovation

BW-20805: Six-monthly prophylaxis shows promise

An open-label, multicenter, phase 2 study is investigating BW-20805, a GalNAc-conjugated siRNA targeting plasma prekallikrein, in adults with HAE types I/II.

Updated data demonstrated reductions in HAE attack rates of 93–99% across the dosing regimens studied, with between 60–83% of participants remaining attack-free. Sustained suppression of plasma prekallikrein supported continued evaluation of six-monthly dosing. Treatment was generally well tolerated, with mainly mild injection-site reactions reported, and no treatment-related serious adverse events.

Abstract: Long-Acting Prophylactic Injection BW-20805: Remarkable and Sustained HAE Attack Reduction — Updated Analysis from an Ongoing Phase 2 Study.

Navenibart: Benefits maintained across patient subgroups

Data from a post hoc analyses of the phase 1b/2 ALPHA-STAR trial (NCT05695248) supported navenibart, a monoclonal antibody targeting plasma kallikrein, as a potential long-acting therapy across patient characteristics.

Findings showed consistent reductions in HAE attack rates across subgroups defined by baseline attack frequency, age and body mass index. Improvements were also observed in attacks requiring on-demand treatment and moderate-to-severe attacks, supporting continued evaluation of navenibart across a broad HAE population.

Abstract: Clinical outcomes with navenibart according to baseline attack rate, body mass index, and age: results of the ALPHA-STAR trial.

Donidalorsen: One-year OASISplus update

Data from the OASISplus open-label extension study (NCT05392114) demonstrated sustained efficacy with donidalorsen, a prekallikrein-directed antisense oligonucleotide approved in the US and Europe for prevention of HAE attacks.

At Week 52, the mean HAE attack rates had decreased by 94% in the Q4W dosing group and 95% in the Q8W dosing group relative to baseline in the original study period. Additionally, 76% of patients were attack-free for at least 6 consecutive months between Weeks 4-52. Clinically meaningful improvements in quality-of-life accompanied reductions in attacks across multiple anatomical sites.

The safety profile remained favourable, with most adverse events being mild or moderate. Injection-site discoloration occurred in 6% of participants, and was the most common treatment-related TEAE.

Abstract: Donidalorsen For The Treatment Of Hereditary Angioedema: 1-Year Results From The OASISplus Open-Label Extension Cohort.

Looking ahead

The studies presented at EAACI Congress 2026 illustrate the breadth of innovation underway in HAE. Gene-editing strategies are moving into late-stage clinical development, oral therapies continue to expand options for both acute treatment and prophylaxis, and next-generation long-acting agents are exploring increasingly convenient dosing schedules.

Although many of these therapies remain investigational, the data presented at this year’s meeting highlight continued progress towards broadening treatment options and reducing the burden of disease management for people living with HAE.