Intellia Therapeutics reports Phase 3 data for lonvo-z in hereditary angioedema, showing 87% attack reduction and supporting a one-time CRISPR treatment approach.
Written By: Farha Farheen, Pharm D
Reviewed By: Pharmacally Editorial Team
Intellia Therapeutics has reported positive topline results from its global Phase 3 HAELO trial evaluating lonvo-z, an investigational in vivo gene editing therapy for hereditary angioedema (HAE), a rare genetic disorder characterized by recurrent and potentially life-threatening swelling episodes.
The company has also initiated a rolling biologics license application submission to the U.S. Food and Drug Administration and is targeting a potential U.S. launch in the first half of 2027.
The randomized, double-blind, placebo-controlled Phase 3 trial enrolled 80 patients aged 16 years and older with Type I or Type II HAE, of whom 52 received a single 50 mg dose of lonvo-z and 28 received placebo. Nearly half of participants were from the United States, and 71% were on long-term prophylaxis therapy at baseline, which was discontinued prior to dosing.
Lonvo-z met the primary endpoint, reducing HAE attacks by 87% compared to placebo during the six-month evaluation period, with a mean monthly attack rate of 0.26 versus 2.10 (p<0.0001). All key secondary endpoints were also achieved, including 62% of treated patients remaining both attack-free and therapy-free over six months compared with 11% in the placebo arm. All patients who received lonvo-z remained free from long-term prophylaxis at the data cutoff.
The therapy demonstrated a favorable safety profile, with treatment-emergent adverse events limited to mild to moderate infusion-related reactions, headache and fatigue, and no serious adverse events reported.
These findings build on earlier clinical data presented by Intellia at the American Academy of Allergy Asthma & Immunology Annual Meeting 2026, where Phase 1/2 results showed a 96% reduction in HAE attack rates and 97% of patients remaining attack-free at three years following a single dose of lonvo-z, with additional analyses supporting durability and disease control.
Lonvo-z is designed as a one-time outpatient therapy using CRISPR/Cas9 technology to inactivate the KLKB1 gene, reducing kallikrein and bradykinin levels that drive HAE attacks.
Intellia’s CEO, John Leonard, stated that the data support the potential of a single-dose therapy to provide sustained freedom from attacks and reduce dependence on ongoing treatment, marking a milestone for gene editing.
Clinical investigator Aleena Banerji noted that despite existing therapies, many patients continue to experience breakthrough attacks and treatment burden, and a one-time treatment could offer a meaningful alternative if approved.
Additional data from the trial will be presented at the 2026 European Academy of Allergy and Clinical Immunology Congress.
Hereditary angioedema affects approximately one in 50,000 individuals and typically requires lifelong preventive treatment, with breakthrough attacks remaining common despite current options.
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