1 lonvo-z dose keeps most HAE patients attack-free up to 3 years
Pooled trial data show 97% don’t need long-term prophylaxis
Most people with hereditary angioedema (HAE) who received a single, 50 mg dose of lonvoguran ziclumeran, also called lonvo-z and formerly known as NTLA-2002, in a clinical trial have remained free from swelling attacks and no longer require long-term preventive therapy up to three years of follow-up.
That’s according to data from a pooled analysis from an ongoing Phase 1/2 clinical trial of the therapy, being developed by Intellia Therapeutics.
Researchers shared the data in an oral presentation, “Two-Year Durability/Safety of One-Time Lonvoguran Ziclumeran (Lonvo-z, NTLA-2002) 50mg in Patients with Hereditary Angioedema,” at the 2025 American College of Allergy, Asthma & Immunology annual meeting, held last month in Orlando, Florida.
“[These] data further support our belief that lonvo-z could completely redefine the HAE treatment landscape,” John Leonard, MD, Intellia’s president and CEO, said in a company press release.
‘Unpredictable’ condition puts burden on patients
HAE is caused by mutations that lead to the excessive production of bradykinin, a signaling molecule that causes blood vessels to widen and leak fluid into surrounding tissues. This leakage triggers episodes of swelling that can be painful, disabling, and in some cases, life-threatening.
“[HAE] is a condition with significant burden that is marked by the unpredictable nature of when the next attack could occur, the painful and often prolonged swellings themselves as well as the need for lifelong treatment,” said Danny Cohn, MD, PhD, an internist in the department of vascular medicine at Amsterdam University Medical Center, who presented the data at the conference.
Lonvo-z is an investigational one-time treatment designed to permanently inactivate the KLKB1 gene, which provides instructions for making a precursor of kallikrein — the enzyme that drives bradykinin production. By inactivating KLKB1, the therapy aims to reduce kallikrein activity, lower bradykinin levels, and ultimately prevent swelling attacks over the long term.
The new analysis includes data from 32 people with HAE who received a single 50 mg infusion of lonvo-z in the ongoing Phase 1/2 clinical trial (NCT05120830). In the Phase 1 part of the trial, 10 adults with HAE received a one-time infusion of lonvo-z at doses of 25 (three people), 50 (four people), or 75 mg (three people) to assess safety and early biological activity.
The Phase 2 portion enrolled additional adults with HAE types 1 or 2, of whom six received a 25 mg dose, 11 received a 50 mg dose, and six were given a placebo. All participants were followed for 16 weeks, or approximately four months.
Previous results showed most patients treated with lonvo-z were free from swelling attacks in the four months after receiving the gene-editing therapy in the Phase 2 part of the study, with most from the Phase 1 portion experiencing no swelling attacks for two years or longer.
31 of 32 patients free of HAE attacks
After the Phase 2 portion was unblinded, participants who had initially received the suboptimal 25 mg dose or placebo were offered a single 50 mg infusion. This brought the total number of people who ultimately received the 50 mg dose to 32, forming the pooled group included in the new analysis.
Across this group, 31 of 32 participants (97%) were both attack-free and no longer using long-term preventive (LTP) therapy, as of the latest follow-up, including 10 of the 11 patients who originally received the 50 mg dose in Phase 2 part. The remaining patient still experienced a meaningful benefit, with a 59% reduction in the monthly attack rate.
A total of 24 patients (75%) maintained this status for at least seven months and up to 32 months, or nearly three years, in those with the longest follow-up.
Blood kallikrein levels also showed a deep and stable reduction across the group, with mean levels dropping by 89% at month 24, or about two years, data showed.
Across all 32 participants, one treatment-emergent serious adverse event was reported, which was resolved without long-term complications. Infusion-related reactions were the most common side effects. These were generally mild, resolved quickly, and did not prevent any patient from receiving the full infusion. No treatment-related side effects were observed beyond the first 28 days after dosing.
“With up to three years of follow-up, the vast majority of patients who received a one-time 50 mg dose of lonvo-z – including 10 of our original 11 patients who received this dose in Phase 2 – were both attack-free and LTP-free as of the data cutoff,” Leonard said.
Intellia is conducting a Phase 3 clinical trial, called HAELO (NCT06634420), to evaluate the efficacy of lonvo-z in reducing the frequency of swelling attacks. The study, which recently completed enrollment and began dosing its first participant earlier this year, is testing the therapy in about 60 adults and adolescents with HAE type 1 or 2.
Participants are being randomly assigned to receive either a single infusion of lonvo-z or a placebo. The trial’s main goal is to determine whether lonvo-z can reduce the frequency of swelling attacks over a six-month evaluation period, using the 50 mg dose identified as the optimal biological dose in Phase 1/2.
If the findings are positive, results from HAELO could support Intellia’s plans to seek approval of lonvo-z in 2026, with a potential launch in the U.S. as early as 2027, pending approval.
“We are looking forward to our approaching topline readout from our Phase 3 HAELO clinical trial by mid-2026,” Leonard said.
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