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

HAELO Phase 3: Lonvo-z Secondary Endpoints, QoL Data Detailed at EAACI

Lonvoguran ziclumeran (lonvo-z; Intellia Therapeutics), a one-time in vivo CRISPR gene-editing therapy for

, continued to demonstrate compelling efficacy across secondary endpoints in the phase 3 HAELO trial. The team presented new HAELO data in a late-breaking oral session at the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress 2026 in Istanbul and simultaneously published it in the 

 following the meeting, 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, said the secondary endpoint data exceeded her expectations despite entering phase 3 with cautious optimism.

“Going into any phase 3 study [is] unpredictable [in terms of] what the efficacy is going to be,” Banerji said. “It was very exciting to see that not only did the data match what was being seen in the prior phase 1 and phase 2 study, but it really exceeded expectations."

Secondary Endpoints and HAE Attack Reductions

As previously reported, HAELO met its primary endpoint with an 87% reduction in mean monthly attacks in the lonvo-z arm versus placebo during the efficacy evaluation period from weeks 5 to 28.

 The newly disclosed secondary data built further on that result.

The monthly rate of moderate and severe attacks was reduced by 91% in patients receiving lonvo-z compared with placebo (0.11 vs. 1.23; 

 <.0001), and the monthly rate of attacks requiring on-demand treatment fell by 89% (0.19 vs. 1.79; 

Banerji called the absence of non-responders a particularly meaningful finding. Patient-level data demonstrated that all patients in the lonvo-z arm experienced attack-rate reductions from baseline during weeks 5 to 28.

"It's rare that we see that when you look across a lot of other trials or even outside of hereditary angioedema," Banerji said.

Quality of Life Improvements With Lonvo-Z

Patients receiving lonvo-z experienced a mean improvement of 17.04 points in the Angioedema Quality of Life (AE-QoL) total score compared with approximately 6.5 points in the placebo arm, a difference that exceeded the 6-point threshold considered clinically meaningful.

Banerji said that threshold context matters when interpreting the magnitude of that gain. “A 17-point change far exceeds what we believe is clinically meaningful," she noted. Patients in the trial reported being able to think differently about work, school, and travel—including activities like taking a cruise—without organizing their lives around the fear of an impending attack.

"It's the constant fear of that next attack and when it's going to occur," Banerji said. "Being able to change that and seeing this significant improvement in quality-of-life matching what we're seeing with efficacy is really promising for the real world."

The HAELO population included patients across a range of prior treatment histories, from those naive to long-term prophylaxis (LTP) to those who were attack-free on existing regimens. Notably, 20% of enrolled patients reported having complete disease control as their best response to prior long-term prophylaxis therapies and yet still chose to enroll.

Banerji addressed why patients already well-controlled on LTP would pursue an investigational gene editing therapy: the burden of treatment itself, including insurance approvals, supply management, and injection schedules.

“Just because they're doing well on long-term prophylaxis in terms of not having attacks or feeling that they are attack-free isn't the only aspect of hereditary angioedema,” she said.

All treatment-emergent adverse events (TEAEs) reported in the lonvo-z arm were mild or moderate, with no serious adverse events observed. The most common TEAEs exceeding placebo rates were infusion-related reactions, headache, fatigue, back pain, and upper respiratory tract infection.

Banerji said the safety monitoring focus centered on liver function, given the hepatic targeting mechanism of an in vivo CRISPR therapy. No transient or persistent elevations in liver function tests were observed, and infusion reactions resolved without interrupting dosing in any patient.

Plasma kallikrein levels decreased substantially by the first measurement at day 15, reached a steady state by week 5, and remained stable through the data cutoff of February 10, 2026, with all patients remaining LTP-free as of that date. 

Banerji said durability questions will require continued follow-up but drew confidence from the longer-term phase 1 and phase 2 data.

A rolling BLA submission for lonvo-z was initiated in April, and the company continues to anticipate regulatory approval and a US launch in the first half of 2027.

 When asked which patients she would prioritize, Banerji said her view has shifted toward broad candidacy.

"I think that every patient is eligible," she said. "The concerns are going to be around insurance and navigating some of those challenges, but in terms of talking to patients… we are going to help them understand that this is a newer treatment that's coming up on the market...and then go through all of the data, the efficacy, the safety concerns, the potential benefit, [and] risks. [We] help them think through this in a shared decision-making process so that they themselves can be the person that decides [if] is this the right treatment for them.”

Editor’s note: Reported disclosures for Banerji include CSL Behring and BioCryst Pharmaceuticals.

Intellia Therapeutics. Intellia Therapeutics Reports Additional Positive Phase 3 Results for Lonvoguran Ziclumeran (lonvo-z) in Patients with Hereditary Angioedema. June 13, 2026. 

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

Derman C. Single-Dose Lonvo-z Cuts HAE Attacks by 87% in Phase 3 Trial, With Aleena Banerji, MD. HCPLive. Published May 11, 2026. 

https://www.hcplive.com/view/single-dose-lonvo-z-cuts-hae-attacks-87-phase-3-trial-aleena-banerji-md

Videos

Aleena Banerji, MD, reviews HAELO secondary data: 91% reduction in moderate/severe attacks, 17-point QoL gain, and zero non-responders for lonvo-z.

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

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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