Intellia Reports Positive Phase 3 Results in HAE, a First for an In Vivo Gene Editor

Rare Daily Staff

Intellia Therapeutics said its experimental gene-editing treatment for hereditary angioedema met the main goals in a phase 3 trial, marking the first positive late-stage readout for an in vivo CRISPR therapy.

The company said the data support a planned filing with the U.S. Food and Drug Administration for approval to market the therapy, raising the possibility of a U.S. launch in the first half of 2027, if the treatment is approved.

The results could make lonvo-z the first one-time treatment for HAE, a shift that would change how the disease is managed. Today, many patients rely on preventive medicines that can require frequent injections or daily pills, often for life. If the benefits seen in HAELO hold up over time, the therapy could offer a new option for patients seeking relief from both attacks and the burden of chronic treatment.

Hereditary angioedema, or HAE, is a rare inherited disorder that causes sudden, recurring swelling attacks that can affect the face, throat, abdomen, arms, legs, and other parts of the body. The attacks can be painful, unpredictable, and potentially life-threatening if they involve the airway, and many patients need long-term preventive therapy to keep episodes under control. Even with current medicines, some patients continue to have breakthrough attacks and must take chronic treatment for years.

Intellia’s lonvoguran ziclumeran, or lonvo-z, is designed as a one-time infusion given in an outpatient setting. It uses CRISPR gene-editing technology to inactivate the KLKB1 gene, which is expected to lower kallikrein and bradykinin, two key drivers of swelling in HAE. Intellia says the goal is to give patients prolonged protection from attacks without the burden of ongoing medication.

In the global HAELO trial, 80 patients were enrolled, with 52 receiving lonvo-z and 28 receiving placebo. The study met its primary endpoint, with lonvo-z reducing attacks by 87 percent versus placebo during the six-month efficacy period, and the mean monthly attack rate falling to 0.26 in the treatment group compared with 2.10 in the placebo group.

The trial also met all key secondary endpoints with statistical significance, including a 62 percent rate of patients who were both attack free and therapy free during that period, compared with 11 percent in the placebo group.

The most common treatment-related side effects were infusion-related reactions, headache, and fatigue, and all adverse events reported by the data cutoff were mild or moderate. Intellia said there were no serious adverse events in the lonvo-z arm as of February 10, and all patients who received the therapy at baseline or after crossing over from placebo remained off long-term prophylaxis.

Intellia said it has started a rolling biologics license application with the FDA, a process that allows parts of the filing to be submitted and reviewed as they are completed.

“As the first phase 3 data reported for an in vivo gene editing therapy, today’s HAELO results represent a profound milestone for Intellia, the broader CRISPR and precision medicine fields and, most importantly, the HAE community,” said John Leonard, president and CEO of Intellia. “For those patients who have spent years battling unpredictable breakthrough swelling attacks, anxiety about their next attack, or the many burdens associated with chronic prophylactic treatment, lonvo-z represents a potential paradigm shift in treatment. 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, president and CEO of Intellia