Pooled phase 1/2 results indicate that lonvo-z achieves durable reductions in plasma kallikrein, with most patients remaining attack-free and prophylaxis-free for up to three years.
Positive pooled phase 1/2 data, shared in an oral presentation at the American College of Allergy, Asthma & Immunology (ACAAI) 2025 Annual Scientific Meeting in Orlando, Florida, show that a one-time treatment with lonvoguran ziclumeran (lonvo-z) led to deep, durable, and stable reductions in plasma kallikrein levels in patients with hereditary angioedema (HAE). Among patients receiving a single 50 mg dose, nearly all remained attack-free and long-term prophylaxis (LTP)-free for extended periods, with a well-tolerated safety profile observed for up to three years of follow-up.1
About lonvoguran ziclumeran
Lonvoguran ziclumeran (lonvo-z) is an investigational CRISPR/Cas9-based in vivo gene-editing therapy designed to prevent HAE attacks by inactivating the kallikrein B1 (KLKB1) gene, which encodes prekallikrein, the precursor of plasma kallikrein. By directly targeting the source of kallikrein overproduction, lonvo-z aims to provide a long-lasting, one-time treatment for patients with HAE Types I or II, potentially eliminating the need for lifelong prophylactic therapy.
Study design and methodology
The pooled analysis combined data from all 32 participants who received a single 50 mg intravenous infusion of lonvo-z in the ongoing global phase 1/2 clinical trial (NCT05120830). The study is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics in adults living with HAE Types I or II.
Of these patients, 15 received the 50 mg dose in the initial study phase, while 17 additional participants were treated following unblinding of the Phase 2 portion. Data were analyzed as of 29 August 2025.
Efficacy outcomes
Deep and sustained reductions in plasma kallikrein levels were observed in all patients, with an average reduction of 89% at 24 months. Among the 32 participants, 31 (97%) remained attack-free and long-term prophylaxis (LTP)-free at the data cutoff, and 24 (75%) maintained this response for at least seven months (up to 32 months for those with the longest follow-up).
In the phase 2 cohort, 10 of 11 patients who received the 50 mg dose were both attack-free and LTP-free, demonstrating durable benefit. The remaining patient achieved a 59% reduction from baseline in monthly attack rate.
Safety findings
The data reported showed lonvo-z to have a well-tolerated safety profile. The most frequent treatment-emergent adverse events (TEAEs) within 28 days of infusion were infusion-related reactions, fatigue and headache. Beyond 28 days, the most common TEAEs were nasopharyngitis, upper respiratory tract infection, back pain, arthralgia and COVID-19.
No long-term safety risks were identified over up to three years of follow-up. One serious adverse event, a pulmonary embolism in a patient with multiple risk factors, occurred one year post-infusion and resolved without sequelae. No clinically significant changes in liver enzymes or coagulation parameters were reported.
Clinical significance
The pooled data indicate that a one-time dose of lonvo-z could offer durable, attack-free protection for individuals living with HAE, potentially transforming disease management by removing the need for ongoing prophylactic therapy. The therapy continues to be evaluated in the phase 3 HAELO trial, which completed enrollment in September 2025 and is expected to read out mid-2026.
Commenting on the findings, study investigator Dr Danny Cohn, Department of Vascular Medicine, Amsterdam University Medical Center, noted that these data “offer hope that lonvo-z could significantly reduce or remove the burdens of HAE for many patients via a one-time treatment.”
Hereditary angioedema remains a rare but serious condition characterised by unpredictable swelling attacks affecting the skin, gastrointestinal tract and airway.2 While advances in targeted therapies over the past decade, and this year alone, have improved prevention and control, many patients continue to experience breakthrough attacks and substantial treatment demands. The emergence of novel approaches such as gene-editing and silencing therapies could represent another shift in the management of HAE, offering the possibility of long-term remission for patients living with this condition
References
- Intellia Therapeutics Presents Positive Pooled Phase 1/2 Data of Lonvoguran Ziclumeran (lonvo-z) in Patients with Hereditary Angioedema. Press release. Intellila Therapeuics. 8 November, 2025. Accessed November 1, 2025 at https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-presents-positive-pooled-phase-12-data
- Pines JM, Poarch K, Hughes S. Recognition and Differential Diagnosis of Hereditary Angioedema in the Emergency Department. J Emerg Med. 2021;60:35–43.
Disclosure: This article was created by the touchDERMATOLOGY team utilizing AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: Lonvoguran ziclumeran: CRISPR-based therapy shows potential as a durable, one-time disease control in hereditary angioedema in early phase 1/2 results. TouchDERMATOLOGY. 13 November, 2025.
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