Intellia Therapeutics Reports Positive 3-Year Phase 1 Data for Lonvo-z in Hereditary Angioedema — Highlights Durable Benefit and Safety
Intellia Therapeutics, a leading clinical-stage genome-editing biotechnology company, today presented updated and extensive follow-up data from the Phase 1 portion of its ongoing Phase 1/2 study evaluating lonvoguran ziclumeran (lonvo-z, also known as NTLA-2002) in patients with hereditary angioedema (HAE). The data, which encompass up to 3 years of follow-up after a single infusion of the treatment, were shared in an oral presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2025, held from June 13–16 in Glasgow, United Kingdom.
Intellia’s ongoing study stands at the intersection of biotechnology and genomic medicine, employing its proprietary CRISPR/Cas9 platform to enable permanent, targeted genome-editing. This approach holds the promise of delivering durable, possibly one-time treatments for patients suffering from HAE — a rare, autosomal dominant condition that typically involves unpredictable attacks of swelling — by directly reducing plasma kallikrein, a key driver of attacks.
Durable Benefit and Positive Clinical Outcomes
“Today’s results underscore the promising potential of Intellia’s approach to genome-editing therapy — a one-time treatment that has been well tolerated and offers a highly differentiated, durable effect for patients suffering from a serious disease,” said John Leonard, M.D., President and Chief Executive Officer of Intellia Therapeutics. “It’s profoundly encouraging to see all 10 patients in the Phase 1 portion of this study remain free from both attacks and chronic therapy nearly two years after their infusion — a reflection of the strong and sustained kallikrein reduction we’re seeing — and we’re looking forward to the eventual results from our ongoing Phase 3 HAELO study, which we anticipate delivering in the first half of 2026. This data further highlights the strong value we believe this approach can bring to patients, physicians, and payers.”
Hereditary angioedema typically involves attacks of severe swelling — often affecting the face, limbs, gastrointestinal tract, or upper airways — which can be painful, disfiguring, and, in some cases, life-threatening. Currently, many patients remain dependent on prophylactic or rescue medications to reduce attack severity and frequency. The ability to produce a durable, attack-free state with a single infusion could profoundly improve patients’ quality of life.
Patient Impact and Quality of Life Improvement
“People living with HAE often report a reduced quality of life because they constantly live with the uncertainty of their next attack — whether or when it might come — or are reminded of their condition by their reliance on chronic prophylactic therapy,” said Dr. Joshua Jacobs, Medical Director, Allergy and Asthma Clinical Research, Inc. “Based on these data, it’s reasonable to expect that lonvo-z could enable patients to be free from both physical attacks and the daily burden of prophylactic treatments, offering them greater peace of mind and a significant improvement in their overall well-being.”
Deep, Durable Reduction in Kallikrein and Attacks
In the Phase 1 portion of the study, a total of 10 patients received a single intravenous infusion of lonvo-z at one of the following dose levels: 25 mg (n = 3), 50 mg (n = 4), or 75 mg (n = 3). The study’s main endpoints included plasma kallikrein protein levels and attack rate, with follow-up extending up to 3 years after infusion.
As of the February 12 data cutoff, all 10 patients remained attack-free and treatment-free for a medial follow-up of nearly two years. Furthermore, a single infusion of lonvo-z resulted in a dramatic 98% mean reduction in attack rate, which was sustained over the follow-up period, when measured against their respective baseline attack rates. Importantly, plasma kallikrein was profoundly reduced in a dose-dependent manner across all patient cohorts and remained suppressed through the most recent follow-up.
This sustained reduction in plasma kallikrein directly correlates with the dramatic and durable attack-free state observed in all patients — a strong affirmation of the potential for a “one-and-done” genomic medicine approach in hereditary angioedema.
Safety Profile and Tolerance
Across all the investigated dose cohorts, lonvo-z was well tolerated and demonstrated a favorable safety profile, consistent with previously presented data at the 2024 EAACI meeting. The most frequently reported adverse events during follow-up were infusion-related reactions (IRRs), which were predominantly grade 1 (mild) and resolved without further complications. Importantly, all patients successfully received their full infusion dose without needing to discontinue due to side effects.
With up to 3 years of follow-up, there have been no treatment-emergent serious adverse events or treatment-related adverse events after the initial 28-day follow-up period — further validating the strong safety profile for this one-time intervention.
Clinical Development Plans and Future Outlook
Intellia’s ongoing Phase 3, randomized, double-blind, placebo-controlled HAELO trial is currently assessing the safety and efficacy of lonvo-z at the 50 mg dose in a larger patient population. The Company recently successfully completed its patient screening process ahead of schedule, with more than half of the participants screened in the United States. This trial is no longer enrolling, and additional enrollment details will be provided in future announcements.
Looking forward, new and longer-term data from the Phase 2 portion of the ongoing Phase 1/2 study is expected to be presented in the second half of 2025, adding depth to the growing body of knowledge surrounding lonvo-z. Furthermore, Intellia plans to submit a biologics license application (BLA) in 2026 in support of a potential U.S. launch in 2027 — a significant milestone in its mission to bring forward a one-time, potentially curative treatment for hereditary angioedema.
This ongoing progress highlights the strong potential for genome-editing therapy to redefine the standard of care for HAE — freeing patients from a lifelong regimen of prophylactic treatments and allowing them to live their lives without the shadow of attacks.
