FDA Grants Priority Review to Intellia’s One-Time CRISPR Treatment for HAE

Rare Daily Staff

The U.S. Food and Drug Administration has granted Intellia Therapeutics Priority Review for lonvoguran ziclumeran, or lonvo-z, the company’s experimental one-time CRISPR gene-editing treatment for hereditary angioedema, setting a decision date of March 10, 2027.

The agency also told the company it is not currently planning to convene an advisory committee meeting to discuss the therapy. If approved, lonvo-z would become the first CRISPR-based gene-editing medicine administered directly in the body, or in vivo, and the first one-time treatment for hereditary angioedema, according to Intellia.

Hereditary angioedema is a rare genetic condition marked by recurrent, unpredictable swelling attacks that can affect the skin, gastrointestinal tract and airways. Attacks can be painful and disabling, while swelling in the throat can be life-threatening.

Existing preventive therapies can reduce attacks but generally require ongoing treatment, including injections, infusions or daily oral medicines. Intellia is seeking to offer a different approach: a single outpatient infusion intended to permanently reduce production of kallikrein, a protein that drives the inflammatory pathway underlying HAE attacks.

Lonvo-z uses CRISPR/Cas9 gene editing to inactivate the KLKB1 gene in the liver. The edit is designed to durably lower kallikrein levels, potentially eliminating or substantially reducing the need for long-term preventive medicines.

Lonvo-z has previously received several expedited development designations, including FDA Orphan Drug and Regenerative Medicine Advanced Therapy designations. It has also received the U.K. Medicines and Healthcare products Regulatory Agency’s Innovation Passport, the European Medicines Agency’s PRIME designation and orphan-drug designation from the European Commission.

“Today marks an important milestone for the patients we are committed to serving and for Intellia’s pioneering work in the field of in vivo gene editing,” John Leonard, Intellia’s president and CEO, said.

The FDA application is supported by results from HAELO, Intellia’s global phase 3 trial of a one-time 50-milligram dose of lonvo-z in adults and adolescents ages 16 and older with Type 1 or Type 2 HAE.

The 80-patient study met its primary endpoint and key secondary endpoints. During the trial’s main efficacy period, from week 5 through week 28, patients treated with lonvo-z had an 87% reduction in mean monthly HAE attacks compared with placebo, Intellia said.

Some 62 percent of patients in the lonvo-z group were both attack-free and free of HAE therapy during the six-month evaluation period, compared with 11 percent of placebo recipients. As of a February 10, 2026, data cutoff, all patients who received lonvo-z either at the start of the study or after crossing over from placebo remained off long-term prophylactic treatment, the company said.

The most common adverse events reported more often with lonvo-z than placebo during the primary observation period were infusion-related reactions, headache, fatigue, back pain and upper respiratory tract infection. Intellia said all treatment-emergent adverse events in the study were mild or moderate and that no serious adverse events occurred in the lonvo-z arm.

The filing represents a significant regulatory test for in vivo CRISPR editing, an approach that aims to make genetic changes inside a patient rather than editing cells outside the body and reinfusing them. Several CRISPR-based treatments have already reached patients through ex vivo approaches, most notably therapies that alter a patient’s blood stem cells outside the body. Lonvo-z, by contrast, is delivered systemically and uses a lipid nanoparticle to carry its gene-editing components to the liver.

That distinction could make the FDA’s assessment especially consequential. The agency will be weighing not only lonvo-z’s reduction in attacks and its apparent ability to eliminate the need for preventive therapy in many participants, but also the durability of the effect and the safety profile of a permanent edit administered in vivo.

Photo: John Leonard, Intellia’s president and CEO