Global clinical trial of HAE gene-editing therapy now fully enrolled
Developer on track to seek FDA approval of lonvo-z late next year
Patient enrollment has been completed in a global Phase 3 clinical trial that’s evaluating lonvoguran ziclumeran, also known as lonvo-z (NTLA-2002), a gene-editing therapy Intellia Therapeutics is developing to prevent swelling attacks in people with hereditary angioedema (HAE).
Dubbed HAELO (NCT06634420), the trial — which began dosing participants early this year — is testing the therapy in about 60 adults and adolescents with HAE types 1 or 2. According to Intellia, nearly half of the enrolled patients are from the U.S.
Top-line data from the study, launched last fall, are anticipated in the first half of 2026.
Meanwhile, Intellia is on track to submit an application to the U.S. Food and Drug Administration (FDA) in the second half of 2026, seeking approval of lonvo-z for HAE. If the therapy wins FDA approval, it would be expected to hit the U.S. market in the first half of 2027.
“Completing HAELO enrollment within nine months since dosing the first patient marks a pivotal moment for the company and reflects the degree of unmet need we are hearing from people living with HAE,” John Leonard, MD, president and CEO of Intellia, said in a company press release announcing the milestone.
“Our momentum remains strong for a planned [application] submission in 2026 as we seek to make this potentially life-changing therapy available to HAE patients starting in the U.S.,” Leonard said.
Swelling attacks in people with HAE are driven by the overproduction of a signaling molecule called bradykinin, which causes blood vessels to widen and become more permeable. That, in turn, allows fluid to leak out and pool into nearby tissues. Bradykinin’s production is controlled by an enzyme called kallikrein.
Global clinical trial testing lonvo-z for preventing HAE swelling attacks
Lonvo-z is a one-time gene-editing therapy that uses CRISPR/Cas9 technology to inactivate the gene that encodes the precursor to the kallikrein enzyme. By reducing kallikrein production and activity, lonvo-z is expected to lower bradykinin production and prevent HAE swelling attacks.
In the Phase 1 part of an ongoing Phase 1/2 clinical trial (NCT05120830), lonvo-z reduced monthly swelling attacks by an average of 98% among 10 adults with HAE after nearly two years of follow-up. All of the participants in this small study were given one of three doses of the gene-editing therapy. More recent data, shared earlier this year, indicated these benefits have been maintained for as long as three years.
In the study’s Phase 2 portion, 27 HAE patients received one of two doses of lonvo-z (25 or 50 mg) or a placebo. Over nearly four months, both doses were shown to substantially lower the number of swelling attacks among participants, with no new safety concerns identified.
Based on results from the Phase 1/2 study, lonvo-z shows great promise to positively transform the HAE treatment paradigm. … We look forward to seeing the Phase 3 top-line data next year.
Intellia expects to present longer-term data from the Phase 2 portion of that trial by the end of this year.
“Based on results from the Phase 1/2 study, lonvo-z shows great promise to positively transform the HAE treatment paradigm,” said Aleena Banerji, MD, HAELO’s principal investigator and a professor at Harvard Medical School. Banerji also serves as clinical director of the allergy and clinical immunology unit at Massachusetts General Hospital.
“We look forward to seeing the Phase 3 top-line data next year,” Banerji said.
HAELO also assessing changes in quality of life among participants
In the HAELO trial, also sponsored by Intellia, participants are being randomly assigned to receive a single 50 mg infusion of lonvo-z or a placebo. The trial’s primary goal is to assess the therapy’s ability to reduce the number of HAE attacks from week five through week 28.
Secondary measures include assessing the proportion of participants who are attack-free within the same timeframe, as well as those achieving responder status — seeing their attack frequency drop by at least 50%, 70%, and 90%.
Changes in quality of life, the number of moderate or severe attacks, and the number of attacks that require on-demand treatment will also be evaluated.
The study’s longer-term goals include assessing the proportion of patients who remain free of prophylaxis — routine treatment to prevent swelling attacks — from week 5 through week 104, or the two-year mark. The percentage of participants who remain attack-free with no long-term prophylaxis will also be examined.
Participants who initially received the placebo in HAELO can switch to the gene-editing therapy at week 28, or after about six months, to assess the impact of lonvo-z on the number of swelling attacks from week 33 through to week 104.
Leonard expressed appreciation to everyone involved in the trial.
“We are deeply grateful to the patients, their families and the trial investigators for their enthusiasm and look forward to sharing topline results from the Phase 3 study next year,” Leonard said.
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