Lonvo-z gene-editing therapy lowers HAE attacks by 87% in Phase 3 trial
More than 60% were attack-free and therapy-free during evaluation
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A single dose of lonvoguran ziclumeran (lonvo-z) left more than 60% of patients with hereditary angioedema (HAE) free of swelling attacks and ongoing therapy during a six-month evaluation period, suggesting it could reduce the need for lifelong preventive therapy if approved.
That is according to topline data from HAELO (NCT06634420), a placebo-controlled Phase 3 clinical study that began dosing early last year. The study is testing how well a single 50 mg infusion of lonvo-z, an experimental gene-editing therapy, prevents swelling attacks in adults and adolescents with HAE type 1 or 2.
“These data affirm lonvo-z’s potential, with one dose, to offer prolonged freedom from both attacks and the need for ongoing therapy,” John Leonard, MD, president and CEO of Intellia Therapeutics, which is developing the gene-editing therapy, said in a company press release.
Intellia starts rolling FDA application for lonvo-z
Intellia initiated a rolling submission of a biologics license application (BLA) to the U.S. Food and Drug Administration (FDA) to seek approval for lonvo-z. A rolling submission lets the company submit portions of the application on an ongoing basis, giving the FDA an opportunity to expedite its review. Intellia plans to complete the BLA submission in the second half of this year. If approved, the company plans to launch lonvo-z in the U.S. in the first half of next year.
“We extend our deep gratitude to the many patients, caregivers and clinicians who have helped advance gene editing science by participating in our clinical trials. It is because of their contribution that we are advancing toward our first potential approval, with the goal of making lonvo-z available to U.S. patients in the first half of 2027,” Leonard said.
In angioedema, attacks of swelling occur when fluid collects in tissues. In HAE, genetic mutations disrupt normal control of a pathway that produces bradykinin, a small protein that widens blood vessels and causes them to leak fluid. Because attacks are unpredictable, and many preventive therapies require ongoing treatment, many patients experience anxiety.
Previously known as NTLA-2002, lonvo-z uses CRISPR gene editing, a technology that can change DNA within cells, to turn off the KLKB1 gene. KLKB1 provides instructions for making a precursor to kallikrein, an enzyme involved in bradykinin production. Lowering kallikrein and bradykinin levels is expected to prevent swelling attacks.
Unlike currently available preventive therapies that often require ongoing dosing, lonvo-z is given as a single infusion into the bloodstream. “For those patients who have spent years battling unpredictable breakthrough swelling attacks, anxiety about their next attack or the many burdens associated with chronic [preventive therapy], lonvo-z represents a potential paradigm shift,” Leonard said.
Most treated patients were free of attacks and ongoing therapy
The HAELO clinical study enrolled 80 patients, ages 16 and older, of whom 52 received lonvo-z at a 50 mg dose and 28 received a placebo. The main goal was to see how much the gene-editing therapy reduced the number of attacks over the six-month efficacy evaluation period. Patients who received lonvo-z had an 87% reduction in attacks compared with those who received a placebo, with an average of 0.26 versus 2.1 monthly attacks.
Researchers also looked at how many patients had no attacks at all and no longer needed ongoing therapy. During the six-month efficacy evaluation period, a significantly higher proportion of patients who received lonvo-z were free of attacks and ongoing therapy compared with those who received a placebo (62% vs. 11%).
After week 28, patients were eligible for an optional blinded crossover, in which those initially assigned to placebo could receive lonvo-z. At the data cutoff, all patients who received lonvo-z, either at the start or at crossover, remained free of long-term preventive therapy.
Favorable safety and tolerability data were observed, consistent with earlier clinical data. All treatment-emergent adverse events reported as of the data cutoff were mild or moderate. The most common events were reactions during the infusion, headache, and fatigue. There were no serious adverse events observed in the lonvo-z arm.
