Six weeks after Intellia Therapeutics reported that it met its primary endpoint in a phase 3 trial of its in vivo gene-editing therapy lonvoguran ziclumeran (lonvo-z) for patients with hereditary angioedema (HAE), the company released additional data showing that the study also met its secondary endpoints with statistical and clinical significance.
Intellia President and Chief Executive Officer John Leonard, M.D., said the data represent the first phase 3 results demonstrating the promise of in vivo CRISPR gene editing, according to a June 13 release. A Jefferies note described lonvo-z as a “paradigm-shifting” one-time treatment, and the data sent the company's stock up Monday morning.
HAE is a rare genetic condition that causes recurrent, unpredictable and potentially life-threatening swelling of the face, limbs, gastrointestinal tract and airways. Lonvo-z is an in vivo CRISPR gene-editing treatment designed to permanently reduce levels of kallikrein, a subgroup of enzymes, by inactivating the kallikrein B1 (KLKB1) gene with a single dose. Kallikrein releases peptides such as bradykinin, which drives HAE when overproduced.
The Haelo study, which randomized 80 patients with HAE, previously showed an 87% reduction (p<0.0001) in mean monthly HAE attacks in the lonvo-z arm compared with the placebo arm during weeks 5 through 28. The trial also found that 62% of patients treated with lonvo-z were attack-free and treatment-free during the six-month efficacy evaluation period, compared with 11% of patients in the placebo group.
Intellia released data June 13 on additional secondary endpoints, showing an 89% reduction in the monthly rate of attacks requiring on-demand treatment from weeks 5 through 28 and a 91% reduction in the monthly rate of moderate to severe attacks during the same period. The company also reported a 17-point improvement by week 28 in the Angioedema Quality of Life score, or AE-QoL, an angioedema-specific patient-reported outcome measure. A 6-point reduction is considered a clinically meaningful improvement in AE-QoL.
“Regardless of age or prior use of long-term prophylaxis therapies, it was observed that a single lonvo-z treatment significantly reduced HAE attacks for all patients during the efficacy evaluation period, with all patients remaining LTP-free as of the data cutoff,” Leonard said in a statement.
The data also revealed a favorable safety and tolerability profile, with only mild or moderate treatment-emergent adverse events reported through week 28. These included headache, fatigue, back pain and upper respiratory tract infection.
Jefferies said the results compare favorably with existing treatments and “have positive implications for commercial positioning” because of lonvo-z’s potential to eliminate the need for lifelong chronic therapy.
The latest data were presented in an oral session at the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress 2026 in Istanbul, Turkey. The trial results were also published simultaneously in the New England Journal of Medicine.
Additional findings showed that the mean monthly attack rate among patients receiving lonvo-z remained below the rate reported during pre-screening through the data cutoff. An analysis also showed reductions in attack rates across all evaluated subgroups.
The treatment is currently the subject of a rolling Biologics License Application (BLA) submission and is expected to launch in the first half of 2027. If approved, it will compete with Ionis Pharmaceuticals’ Dawnzera, which received FDA approval last year after demonstrating an 81% reduction in attacks compared with placebo. Other approved treatments include Takeda’s blockbuster therapy Takhzyro and BioCryst Pharmaceuticals’ Orladeyo.
The key advantage for Intellia is that all of these therapies require chronic administration, whereas lonvo-z is designed as a one-time treatment. As noted in the NEJM article, limitations of the study include the relatively small patient population, limited follow-up and a carefully selected patient sample, although investigators said the cohort was representative of the broader HAE population.