A one-time in vivo CRISPR therapy has significantly reduced attacks in patients with hereditary angioedema in a phase 3 trial.
The double-blind HAELO trial enrolled 80 patients aged 16 years or older with hereditary angioedema due to C1 inhibitor deficiency. Participants were randomly assigned in a 2:1 ratio to receive either a single intravenous infusion of lonvoguran ziclumeran, also known as lonvo-z or NTLA-2002, or placebo. From week 5 to week 28 after infusion, the monthly rate of investigator-confirmed attacks was 0.26 in the lonvo-z group, compared with 2.10 in the placebo group – an 87 percent relative reduction.
Hereditary angioedema is a rare genetic disorder that causes recurrent swelling attacks, which can affect the skin, gastrointestinal tract, or upper airway. Lonvo-z is designed to use CRISPR gene editing to inactivate KLKB1 in the liver, reducing production of plasma prekallikrein and thereby targeting the kallikrein-kinin pathway that drives bradykinin-mediated swelling.
“This is the first time CRISPR therapy has been applied in vivo within a large, double-blind, international Phase 3 trial,” said Danny Cohn, internist at Amsterdam UMC and lead researcher on the study, in the press release. “A total of 80 patients were randomized to receive either lonvoguran-ziclumeran or a placebo.”
Key secondary endpoints also favored lonvo-z. Attacks requiring on-demand treatment were reduced by 89 percent versus placebo, while moderate-to-severe attacks fell by 91 percent. Sixty-two percent of patients receiving lonvo-z were attack-free between weeks 5 and 28 without long-term prophylaxis, compared with 11 percent of patients receiving placebo. Patients in the lonvo-z arm also showed greater improvement on an angioedema-specific quality-of-life measure.
The treatment was generally well tolerated over the reported follow-up period. Adverse events during or after infusion were reported in 92 percent of patients receiving lonvo-z and 86 percent receiving placebo. The most common events seen more often with lonvo-z included infusion-related reactions, headache, fatigue, back pain, and upper respiratory tract infection. No serious or grade 3 or higher adverse events were reported in the lonvo-z group.
“The study demonstrates that the therapy is genuinely effective and safe,” Cohn said in the press release. “This confirmation is exactly what regulatory authorities need to approve the very first in vivo CRISPR gene editing treatment for the market.”
The trial remains limited by sample size and follow-up duration. At the February 10, 2026 data cutoff, median follow-up was 7.5 months, and longer-term monitoring is ongoing. The authors note that additional follow-up will be needed to assess durability and safety, including risks that may emerge outside the controlled setting of a clinical trial.
For patients, the appeal of a single-dose approach is clear. “Patients may no longer need continuous preventative medication, sparing them from the associated side effects,” Cohn said. “Furthermore, this can alleviate treatment burden, reduce drug dependency, lessen the anxiety of future attacks, and ultimately improve quality of life.”
Intellia Therapeutics, which is developing lonvo-z, said it initiated a rolling BLA submission to FDA in April and continues to anticipate potential regulatory approval and a US launch in the first half of 2027. The therapy has received several regulatory designations, including FDA Orphan Drug and Regenerative Medicine Advanced Therapy designations, as well as PRIME designation from the European Medicines Agency.
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