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 hereditary angioedema (HAE) attack rates by 87% compared with placebo in the phase 3 HAELO trial, Intellia Therapeutics shared on April 27, 2026.1,2

In an interview with HCPLive, 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.1

Patients receiving lonvoguran ziclumeran achieved a mean monthly attack rate of 0.26 compared with 2.10 in the placebo arm (P <.0001). Furthermore, a substantial proportion of patients became both attack-free and free from long-term prophylaxis (62% vs 11% on placebo; P <.0001).1

“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.1

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.1

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.3

References

1. 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

2. 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

3. 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