Intellia Therapeutics is set to seek US approval of its in vivo CRISPR gene therapy in hereditary angioedema (HAE) after it showed benefit in a Phase III trial.
The global Phase III HAELO trial, in which HAE patients were treated with a one-time infusion of lonvo-z, met its primary endpoint of reducing attacks by 87% versus placebo, with a mean monthly attack rate of 0.26 in the lonvo-z arm compared with 2.10 in the placebo arm.
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All patients who received lonvo-z at baseline or in crossover after week 28 remained free of long-term prophylaxis (LTP) therapy.
Intellia has reported favourable safety and tolerability data for lonvo-z, with the most common treatment-emergent adverse events (TEAEs) during the primary observation period (infusion through week 28) being infusion-related reactions, headache and fatigue. All TEAEs reported as of 10 February were mild or moderate.
Additional clinical data from HAELO will be presented at the 2026 European Academy of Allergy and Clinical Immunology Congress (EAACI), taking place between 12-15 June in Istanbul, Turkey.
Intellia said it has initiated a rolling Biologics Licence Application (BLA) submission to the US Food and Drug Administration (FDA) to seek regulatory approval, with a potential launch in H1 2027.
Dr Aleena Banerji, Director of Clinical Care, Center for Drug and Vaccine Allergy at Massachusetts General Hospital, and a HAELO principal investigator, said: “Despite the availability of several HAE treatments, many patients continue to experience significant burdens related to the disease, including breakthrough attacks and challenges associated with chronic treatment. The results we are seeing from lonvo-z demonstrate its potential to eliminate the need for chronic medication and related challenges. If approved as a one-time treatment, I would expect lonvo-z to be an appealing option for many patients.”
HAE is a rare genetic condition in which patients experience recurrent and potentially life-threatening swelling (angioedema) attacks in various parts of their body, including the face, upper airway, abdomen and extremities due to an overproduction of bradykinin. Designed as a one-time treatment that is administered in an outpatient setting, lonvo-z is an in vivo CRISPR gene editing candidate that is intended to inactivate the kallikrein B1 (KLKB1) gene to permanently lower kallikrein and bradykinin levels.
Dr John Leonard, Intellia President and CEO, said that this trial marks the first positive readout for an in vivo gene therapy at Phase III.
Leonard said: “For those patients who have spent years battling unpredictable breakthrough swelling attacks, anxiety about their next attack or the many burdens associated with chronic prophylactic treatment, lonvo-z represents a potential paradigm shift in treatment. These data affirm lonvo-z’s potential, with one dose, to offer prolonged freedom from both attacks and the need for ongoing therapy.”
After four years of inactivity, the FDA approved three novel products for HAE in 2025, taking the total number of marketed innovator drugs within the US to 11. FDA approvals in HAE were sparse before 2025, with only one each in 2017, 2018, and 2020. This was followed by a lack of approvals for four years.
Intellia is also investigating another gene therapy, nexiguran ziclumeran (nex-z), in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). Two Phase III trials were put on hold by the FDA due to safety concerns, but the pause has since been lifted in both studies.
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