FDA to decide by March on approval for 1-time gene-editing treatment for HAE
Agency granted priority review to therapy aiming to control swelling
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The U.S. Food and Drug Administration (FDA) is slated to decide by early next year whether or not to approve a one-time gene-editing therapy to potentially control swelling in hereditary angioedema (HAE).
The regulatory agency accepted an application from Intellia Therapeutics seeking approval of its infusion therapy lonvoguran ziclumeran (lonvo-z) — and granted priority review, which shortens the review period from the usual 10 months to about six months. A final decision from the FDA is now expected by March 10, 2027.
If lonvo-z wins FDA approval, it would become the first and only one-time treatment for HAE — and the first gene-editing therapy of its kind to be approved by the FDA for any disease, Intellia stated in a company press release announcing the agency’s acceptance of its biologics license application
“Today marks an important milestone for the patients we are committed to serving,” said John Leonard, MD, Intellia’s president and CEO. “With the FDA’s Priority Review underway, our team is well prepared to deliver this one-time treatment to patients who are waiting for new options.”
HAE, which is marked by swelling in the deep layers of the skin or mucous membranes, is caused by abnormal activity of a signaling molecule called bradykinin. This molecule is produced by an enzyme called kallikrein.
Lonvo-z, previously known as NTLA-2002, is designed to shut down the gene that encodes a precursor of kallikrein. In doing so, the single-use therapy aims to reduce the enzyme’s levels, thereby lowering bradykinin levels to control swelling. The therapy is designed to reduce the risk of swelling attacks in people with HAE, in whom the condition is due to gene mutations.
Lonvo-z works inside the body to treat HAE
To inactivate its targeted gene, lonvo-z uses a molecular technology called CRISPR/Cas9. There are FDA-approved treatments that use this technology ex vivo — meaning cells are removed from a patient’s body, engineered in a lab, and then returned to the body. But lonvo-z has the potential to become the first FDA-approved treatment to use in vivo CRISPR, in which gene editing is performed on cells within the body.
“Backed by compelling Phase 3 data, we believe lonvo-z could fundamentally change the way HAE is treated and are excited by its potential to become the world’s first approved in vivo CRISPR-based therapy,” Leonard said.
Intellia’s application seeking FDA approval of lonvo-z is based mainly on data from a Phase 3 clinical trial called HAELO (NCT06634420). That study enrolled 80 people with HAE types 1 and 2, ages 16 and older. Participants were randomly assigned to receive a one-time infusion of either lonvo-z or a placebo, with the main goal of evaluating the treatment’s effect on swelling attacks over about six months.
The results showed that lonvo-z significantly reduced swelling attack rates, by 87%, compared with the placebo. Nearly two-thirds of patients (62%) given lonvo-z were attack-free over the six-month follow-up period. That compared with about 1 in 10 patients given the placebo.
According to Intellia, all participants given lonvo-z in the trial have not needed further prophylactic, or preventive, treatment as of the latest follow-up.
We believe lonvo-z could fundamentally change the way HAE is treated and are excited by its potential to become the world’s first approved in vivo CRISPR-based therapy.
Safety data indicated that lonvo-z was overall tolerated well; no serious safety problems were documented. The most common side effects associated with the gene-editing therapy were infusion-related reactions, headache, fatigue, back pain, and upper respiratory tract infection.
Joshua Jacobs, MD, an investigator on the HAELO trial and the medical director of the Allergy and Asthma Clinical Research in California, said the news that the FDA is reviewing an application for lonvo-z “is exciting because it advances us one step closer to potentially having a one-time treatment option available for patients who continue to be burdened by this chronic disease.”
Several gene-editing therapies are in development for various conditions. In 2023, the FDA approved Casgevy (exagamglogene autotemcel), an ex vivo, or outside-the-body, treatment, for use in sickle cell disease.
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