FDA Accepts Intellia’s Lonvo-z BLA with Priority Review for Hereditary Angioedema

The U.S. Food and Drug Administration (FDA) has accepted Intellia Therapeutics’ Biologics License Application (BLA) for lonvo-z and granted Priority Review for the investigational one-time treatment for hereditary angioedema (HAE), setting a Prescription Drug User Fee Act (PDUFA) target action date of March 10, 2027. If approved, lonvo-z could become the first approved in vivo CRISPR-based therapy.

FDA Review Advances One-Time HAE Treatment

The FDA accepted the BLA based on data from the global Phase 3 HAELO trial, which evaluated a single 50 mg dose of lonvo-z in adults and adolescents aged 16 years and older with Type 1 or Type 2 HAE. The agency is not currently planning an advisory committee meeting for the application, according to Intellia.

HAE is a rare genetic disorder that causes recurrent, unpredictable episodes of swelling affecting the skin, gastrointestinal tract, airway, and other tissues. Attacks can cause severe pain and disability and may become life-threatening when the airway is involved. Current preventive treatments generally require chronic administration, including intravenous or subcutaneous dosing as often as twice weekly or daily oral therapy. Breakthrough attacks can still occur despite prophylaxis.

CRISPR Editing Targets Kallikrein Production

Lonvo-z uses in vivo CRISPR/Cas9 gene editing to reduce kallikrein production by inactivating the KLKB1 gene. Unlike ex vivo cell therapies, the approach delivers the gene-editing machinery directly into the patient, with the goal of producing a durable therapeutic effect after a single administration.

Kallikrein plays a central role in the kallikrein-kinin pathway that drives swelling during HAE attacks. Reducing kallikrein activity is therefore a clinically validated strategy for preventing HAE attacks.

Phase 3 HAELO Trial Demonstrated Major Attack Reduction

HAELO enrolled 80 patients and reached full enrollment within nine months. The trial met its primary and all key secondary endpoints.

• Attack reduction: During the efficacy evaluation period from weeks 5 through 28, patients receiving lonvo-z experienced an 87% reduction in mean monthly HAE attacks compared with placebo (p<0.0001).
• Attack- and therapy-free status: Sixty-two percent of patients receiving lonvo-z remained entirely free of HAE attacks and HAE therapy during the six-month efficacy evaluation period, compared with 11% of patients receiving placebo (p<0.0001).
• Prophylaxis-free follow-up: As of the February 10, 2026 data cutoff, all patients who received lonvo-z at baseline or after crossover beyond week 28 remained free from long-term prophylaxis therapy.

Safety Profile Remained Favorable

Lonvo-z showed a favorable safety and tolerability profile through the reported follow-up period. Treatment-emergent adverse events occurring more frequently with lonvo-z than placebo included infusion-related reactions, headache, fatigue, back pain, and upper respiratory tract infection.

All reported treatment-emergent adverse events were mild or moderate, and no serious adverse events occurred in the lonvo-z group during the primary observation period through week 28.

Intellia President and CEO John Leonard said the Phase 3 results support the potential for lonvo-z to substantially change how HAE is treated and highlighted the significance of the FDA’s Priority Review.

Regulatory Decision Expected in March 2027

In addition to Priority Review, lonvo-z has received FDA Orphan Drug and Regenerative Medicine Advanced Therapy (RMAT) designations, along with Innovation Passport designation from the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), PRIME designation from the European Medicines Agency (EMA), and Orphan Drug Designation from the European Commission.

The FDA’s March 10, 2027 PDUFA date is the key near-term regulatory milestone. If approved, lonvo-z would introduce a fundamentally different treatment model for HAE: a single outpatient administration intended to permanently modify the kallikrein pathway rather than suppress it through repeated chronic dosing.

Reference

Intellia Therapeutics Announces FDA Acceptance of Biologics License Application with Priority Review for Lonvoguran Ziclumeran (Lonvo-z) for Hereditary Angioedema (HAE). Intellia Therapeutics, 08 September 2026