Lonvoguran ziclumeran

In HAE type 1 and type 2, the body lacks enough working C1 inhibitor, a protein that keeps swelling signals in check, and the result is too much bradykinin, a small protein that makes blood vessels leak fluid into nearby tissue^[11]. Plasma kallikrein is the enzyme that frees bradykinin^[14], and the KLKB1 gene carries the instructions the liver uses to make it^[7].

Lonvo-z packs the CRISPR/Cas9 gene-editing tools into lipid nanoparticles, tiny fat bubbles given by IV that carry their contents to the liver^[1][9]. Inside liver cells the tools cut the KLKB1 gene so it stops working, which Intellia says is meant to lower kallikrein permanently^[1].

In the Phase 2 study, total kallikrein protein in the blood fell by an average of 86% at week 16 after the 50mg dose, while levels on placebo did not change^[6]. In HAELO, Intellia reported that kallikrein levels dropped by the first check on day 15, settled by week 5 and stayed stable through the February 10, 2026 data cutoff^[3]. Because the change is made to the person's own liver cells and is meant to last, lonvo-z is studied as a single dose rather than a repeat treatment^[1].

HAELO (NCT06634420) is a Phase 3, double-blind, placebo-controlled trial at sites in 9 countries, including the US^[8]. It randomized 80 people 16 and older with HAE type 1 or type 2, 52 to a single 50mg infusion of lonvo-z and 28 to placebo^[5]. Intellia said 49% enrolled in the US and 71% were on long-term preventive treatment before the trial, which they stopped before dosing^[2].

From week 5 through week 28, the average monthly attack rate was 0.26 on lonvo-z and 2.10 on placebo, a relative reduction of 87% (95% confidence interval 78-93%)^[5]. Intellia reported that attacks needing on-demand treatment were 89% lower, moderate or severe attacks were 91% lower, and scores on the AE-QoL angioedema quality-of-life questionnaire improved 17.04 points more than on placebo^[3].

The results were published in the New England Journal of Medicine^[5]. Follow-up continues to week 104, and ClinicalTrials.gov lists an estimated completion of September 2027^[8]. The trial left out people with HAE with normal C1 inhibitor and anyone with a known reaction to lipid nanoparticles^[8].

Earlier, in the Phase 2 part of a Phase 1/2 study (NCT05120830), 27 adults were randomized to 25mg, 50mg or placebo. The 50mg dose lowered the monthly attack rate by 77% compared with placebo from week 1 through week 16, and 8 of the 11 people on 50mg had no attacks and needed no other treatment in that period^[6].

Lonvo-z has no US label yet, so its official side effects and warnings are not set. In HAELO, side effects from day 1 through week 28 were reported in 92% of people on lonvo-z and 86% on placebo^[5]. The ones more common on lonvo-z, each in more than 10% of treated people, included infusion-related reactions, headache, fatigue, back pain and upper respiratory tract infections^[5].

No serious side effects and none of grade 3 or higher were reported in the lonvo-z group^[5], and Intellia said every side effect reported through the February 10, 2026 data cutoff was mild or moderate^[2]. In the earlier Phase 1 dose-finding study of 10 adults, infusion-related reactions and fatigue were the most common side effects, with no serious events and no clinically important lab findings^[7].

Intellia's press releases on HAELO do not report liver test results. Because the edit is meant to be permanent, people treated in the trials are followed for years: a long-term follow-up study lists an estimated completion of April 2040^[10]. Any warnings on a US label are for the FDA to decide.

Results from the Phase 1 part of the NTLA-2002 study were published in the New England Journal of Medicine in 2024^[7], and results from the Phase 2 part in 2025^[6]. HAELO began on January 15, 2025^[8], and Intellia said it enrolled all 80 people in 9 months^[1]. On April 27, 2026 Intellia announced that HAELO met its main goal and all key secondary goals and that it had begun a rolling Biologics License Application to the FDA^[2].

Full results were presented at the EAACI allergy congress and published in the New England Journal of Medicine on June 13, 2026^[3][5]. On September 8, 2026 Intellia announced that the FDA had accepted the application with Priority Review and a target action date of March 10, 2027, and that the FDA was not planning an advisory committee meeting^[1].

Lonvo-z holds FDA Orphan Drug and Regenerative Medicine Advanced Therapy (RMAT) designations, PRIME designation from the European Medicines Agency, EU orphan designation and an Innovation Passport from the UK's MHRA^[1]. On November 5, 2026 Intellia said it was preparing for a planned US launch in the first quarter of 2027^[4]; lonvo-z cannot be sold in the US unless the FDA approves it.

Intellia has not disclosed a price. The FDA had not announced a decision as of November 7, 2026.