Aleena Banerji, MD, professor at Harvard Medical School and director of clinical care at the Center for Drug and Vaccine Allergy at Massachusetts General Hospital.

Aleena Banerji, MD

HAE in 2026: New Therapies, Updated Guidelines, the Case for Early Treatment

The treatment landscape for hereditary angioedema is undergoing one of its most significant evolutions in years. Updated international guidelines, pivotal phase 3 data, and promising early-phase results are collectively reshaping how clinicians approach both prophylaxis and acute management of this rare, potentially life-threatening condition.

 about where the field stands and where it is headed.

Guidelines Put Early Treatment Front and Center

have placed renewed emphasis on early, on-demand intervention, formally recommending sebetralstat (Ekterly) as a first-line option for acute treatment of attacks in patients aged ≥ 12 years.

 The oral plasma kallikrein inhibitor was approved by the US Food and Drug Administration (FDA) in July 2025.

Mauro Cancian, MD, PhD, head of the allergy division at the University of Padua and a KONFIDENT trial investigator, said the shift toward an oral agent has meaningfully changed how quickly patients are able to treat attacks.

"What we are emphasizing with our patients, and obviously as a result of the guideline, is that to make treatment more effective, you have to treat the attacks as early as possible," Cancian said. "That means treating at the onset of the attack, because we know that if there is a delay between attack onset and treatment, the drug will be less effective in reducing both the severity and the duration of the attacks."

Data from the phase 3 KONFIDENT study support this urgency. As of January 31, 2025, the median time from attack onset to treatment was just 4 minutes, with a median time to the beginning of symptom relief of 1.79 hours. In the open-label extension, treatment delays shortened further, to under 10 minutes, a figure Cancian attributed to the portability and ease of oral administration.

Cancian cautioned that even patients on long-term prophylaxis require reliable on-demand treatment, as no prophylactic therapy fully eliminates breakthrough attacks. That reality makes the availability of an effective, easy-to-administer acute option all the more critical.

BW-20805: A Long-Acting RNA Interference Approach

Among the investigational therapies attracting attention is 

, a small interfering RNA conjugated with N-acetylgalactosamine that targets hepatocytes via the asialoglycoprotein receptor. Once inside liver cells, it inhibits messenger RNA responsible for producing prekallikrein: the inactive precursor of plasma kallikrein and a central driver of the bradykinin cascade underlying HAE attacks.

Late-breaking phase 2 data presented at the 2026 American Academy of Allergy, Asthma & Immunology annual meeting in Philadelphia showed that BW-20805 achieved high rates of attack-free outcomes at dosing intervals of up to 6 months. Among 10 patients with post-dose efficacy data beyond day 29, 80% remained completely attack-free during the observation period. The highest dose cohort (600 mg every 24 weeks) achieved a 100% reduction in time-normalized HAE attack rate.

Within the first month after administration, prekallikrein levels declined by approximately 90% to 97% depending on the dosing regimen, with reductions remaining stable throughout follow-up.

"The drug BW-20805 is doing what we expect it to do, educing plasma kallikrein activity by more than 90% in a very stable way," said investigator Markus Magerl, MD, of Charité-Universitätsmedizin Berlin.

The therapy's safety profile has been favorable in early analyses, with most adverse events mild and transient, primarily injection-site reactions , and no treatment-related serious adverse events reported. Magerl noted the current findings come from a relatively small phase 2 cohort, and additional data from the completed phase 2 study and an eventual phase 3 trial will be needed to confirm durability and characterize long-term safety.

Lonvoguran Ziclumeran: One-Time CRISPR Therapy Shows 87% Attack Reduction

Perhaps the most headline-generating data came from the 

phase 3 HAELO trial of lonvoguran ziclumeran (lonvo-z)

, an in vivo CRISPR/Cas9 gene editing therapy that targets and inactivates the KLKB1 gene in hepatocytes, reducing kallikrein production and downstream bradykinin generation. Intellia Therapeutics reported top-line results in April 2026.

Patients receiving lonvo-z achieved a mean monthly attack rate of 0.26 compared with 2.10 in the placebo arm — an 87% reduction. More than half (62%) of patients in the treatment arm became both attack-free and free from long-term prophylaxis, compared with 11% on placebo.

Lead investigator Aleena Banerji, MD, professor at Harvard Medical School and director of clinical care at the Center for Drug and Vaccine Allergy at Massachusetts General Hospital, highlighted the significance of those findings, particularly the one-time dosing.

"The biggest benefit that we're seeing here is a one-time treatment that is leading to a significant reduction in attacks similar to the other long-term prophylactic treatments, except that this one does not require any ongoing long-term treatment," Banerji said.

Safety findings to date have been consistent with earlier studies, with no serious adverse events reported during the primary observation period. Common adverse events, all mild to moderate, included infusion-related reactions, headache, and fatigue. Banerji noted that continued follow-up will be essential to monitor for any delayed risks associated with in vivo gene editing.

Intellia has begun a rolling biologics license application submission, expected to be completed in the second half of 2026, with a potential US launch in 2027 pending approval.

These developments reflect a field moving with unusual speed. Patients with HAE now have access to 11 approved treatments in the United States — 6 of them for long-term prophylaxis — with potentially more on the horizon.

"This certainly adds another novel treatment option for prevention of attacks," Banerji said of lonvo-z. "It moves the needle quite a bit for our patients with hereditary angioedema as a one-time treatment with a significantly high rate of efficacy and very good safety data."

For clinicians, the evolving landscape underscores the importance of individualized decision-making, weighing treatment burden, patient preference, and the persistent need for effective on-demand options alongside any prophylactic strategy. As Cancian put it, the goal has not changed, even as the tools to achieve it multiply.

"The main goal [remains] to reduce the number of attacks and to improve the quality of life of patients,” Cancian said.

Check out other allergy news this year here: 

Farkas H, Martinez-Saguer I, Bork K, et al. International Guideline on the Diagnosis and Management of Pediatric Patients With Hereditary Angioedema. 

Zhi Y, Zhao X, Zhu R, et al. Significant HAE Attack Reduction with BW-20805, a Long-Acting Prophylactic Injection- An Ongoing Phase 2 Study in Adult with Hereditary Angioedema. Journal of Allergy and Clinical Immunology. 2026;157(2):AB426. 

doi:https://doi.org/10.1016/j.jaci.2025.12.948

Derman C. Single-Dose Lonvoguran Ziclumeran Cuts HAE Attacks by 87% in Phase 3 Trial. HCPLive. Published April 27, 2026. Accessed April 27, 2026. 

https://www.hcplive.com/view/single-dose-lonvoguran-ziclumeran-cuts-hae-attacks-87-phase-3-trial

Videos

Experts weigh in on a rapidly evolving treatment landscape, from a first-line oral option to a one-time CRISPR therapy showing 87% attack reduction.

Single-Dose Lonvo-z Cuts HAE Attacks by 87% in Phase 3 Trial, With Aleena Banerji, MD

A single dose of lonvoguran ziclumeran (lonvo-z) reduced 

 attack rates by 87% compared with placebo in the phase 3 HAELO trial, Intellia Therapeutics shared on April 27, 2026.

, lead investigator Aleena Banerji, MD, professor at Harvard Medical School and director of clinical care at the Center for Drug and Vaccine Allergy at Massachusetts General Hospital, highlighted the efficacy and safety of lonvoguran ziclumeran for HAE observed over 6 months. Lonvoguran ziclumeran, an in vivo CRISPR-based gene editing therapy, uses CRISPR/Cas9 technology to target and inactivate the KLKB1 gene in hepatocytes, reducing kallikrein production and downstream bradykinin generation.

Patients receiving lonvoguran ziclumeran achieved a mean monthly attack rate of 0.26 compared with 2.10 in the placebo arm (

 <.0001). Furthermore, a substantial proportion of patients became both attack-free and free from long-term prophylaxis (62% vs 11% on placebo; 

“The biggest benefit that we're seeing here is a one-time treatment that is leading to a significant reduction in attacks similar to the other long-term prophylactic treatments, except that this one does not require any ongoing long-term treatment,” Banerji said.

Safety findings to date have been consistent with earlier studies, with no serious adverse events reported during the primary observation period. Common adverse events, all mild to moderate, included infusion-related reactions, headache, and fatigue. Banerji addressed the need for continued follow-up to monitor for delayed risks associated with in vivo CRISPR gene editing.

The trial design required discontinuation of baseline prophylaxis before treatment, which Banerji described as a “higher bar to meet” to demonstrate efficacy. Despite this, lonvoguran ziclumeran achieved significant reductions in attack rates, supporting its potential effectiveness in real-world settings.

Banerji noted that all patients with HAE are candidates for prophylaxis, and shared decision-making will guide adoption if approved. She added that ongoing follow-up, including multi-year safety and efficacy data, will be critical in defining the therapy’s role.

“[Lonvoguran ziclumeran is a] really exciting advance for our patients with hereditary angioedema,” she said. “We have 11 available treatments in the United States, 6 of them for long-term prophylaxis, and so this certainly adds another novel treatment option for prevention of attacks. It moves the needle quite a bit for our patients with hereditary angioedema as a one-time treatment with a significantly high rate of efficacy and very good safety data.”

Intellia Therapeutics has begun a rolling biologics license application (BLA) submission, which is expected to be completed in the second half of 2026, with a potential US launch in 2027 if approval is granted.

Intellia Therapeutics. Intellia Therapeutics reports positive phase 3 results in hereditary angioedema, marking a global first for in vivo gene editing. April 27, 2026. 

https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-reports-positive-phase-3-results

Intellia Therapeutics Initiates Rolling Submission of Biologics License Application to FDA for Lonvoguran Ziclumeran (lonvo-z) as a One-Time Treatment for Hereditary Angioedema - Intellia Therapeutics. Intellia Therapeutics. Published on April 27, 2026. Accessed April 27, 2026. 

https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-initiates-rolling-submission-biologics

Phase 3 HAELO data show an 87% reduction in hereditary angioedema attack rates with a one-time CRISPR therapy. Banerji discusses efficacy, safety, and durability.

Aleena Banerji, MD

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