Cambridge, Massachusetts-based Intellia Therapeutics, Inc. (Nasdaq: NTLA) announced that the US FDA has accepted its Biologics License Application (BLA) and granted Priority Review for lonvoguran ziclumeran (lonvo-z; formerly NTLA-2002), an in vivo CRISPR/Cas9 gene editing therapy targeting the KLKB1 gene, for the treatment of hereditary angioedema (HAE). The agency set a Prescription Drug User Fee Act (PDUFA) target action date of March 10, 2027, and advised Intellia it is not currently planning to convene an advisory committee.
The BLA is supported by data from the Phase III HAELO trial, a randomized, double-blind, placebo-controlled study enrolling 80 adults and adolescents aged 16 years and older with Type I or Type II HAE. A single 50 mg intravenous dose of lonvo-z reduced mean monthly HAE attacks by 87% versus placebo during the six-month efficacy evaluation period (weeks 5 to 28; p<0.0001). On the key secondary endpoint, 62% of patients in the lonvo-z arm were entirely attack-free and free from long-term prophylaxis (LTP) therapy for the full evaluation period, compared with 11% in the placebo arm (p<0.0001). Additional data presented at the European Academy of Allergy and Clinical Immunology Annual Congress in June 2026 and simultaneously published in the New England Journal of Medicine showed a 91% reduction in moderate and severe attacks (p<0.0001) and a 17-point improvement in Angioedema Quality of Life score versus placebo (p<0.0001). All treatment-emergent adverse events through week 28 were mild or moderate, with no serious adverse events in the lonvo-z arm.
Lonvo-z works by permanently inactivating the KLKB1 gene in hepatocytes via a single infusion, reducing plasma kallikrein production and suppressing the bradykinin overproduction that drives HAE attacks. Plasma kallikrein levels decreased substantially by day 15 and remained stable through the February 10, 2026 data cutoff, consistent with durable genomic editing.