Intellia is seeking FDA approval for what could be the first in vivo CRISPR gene editing therapy

The company's treatment for hereditary angioedema reduced attacks by 87% vs. placebo in a Phase 3 trial, clearing the way for a potential 2027 launch

Intellia Therapeutics has initiated a rolling application with the FDA seeking approval for lonvoguran ziclumeran, known as lonvo-z, a one-time treatment for hereditary angioedema that would become the first in vivo CRISPR-based gene editing therapy if cleared by regulators.

Positive Phase 3 HAELO trial results paved the way for the filing, with lonvo-z cutting the rate of hereditary angioedema attacks by 87% against placebo across a six-month evaluation window, Intellia said. The trial met its primary and all key secondary endpoints. At the six-month mark, 62% of lonvo-z recipients achieved attack-free status without other therapies, compared with only 11% of placebo patients, according to Biospace.

Regarding safety, Intellia characterized the lonvo-z tolerability data as "favorable," with infusion-related reactions, headaches, and fatigue among the most common adverse events. No serious side effects emerged, and the company disclosed no instances of liver toxicity.

Liver safety had been a focus for analysts following a patient death in a separate trial of a different Intellia treatment. That patient was participating in a Phase 3 nex-z study targeting transthyretin amyloidosis and died days after liver enzyme levels spiked to a severe grade, according to CNBC. The FDA had paused two Phase 3 studies of nex-z before lifting the hold last month.

At the molecular level, lonvo-z deploys CRISPR/Cas9 to permanently switch off the KLKB1 gene inside liver cells, lowering production of kallikrein — the protein whose overactivity triggers the swelling cascades seen in hereditary angioedema. A single multi-hour infusion delivers the full course of treatment, Intellia said, contrasting with existing management options that demand ongoing dosing schedules as frequent as twice-weekly injections or daily pills.

Hereditary angioedema is a rare genetic disease that causes severe, recurring, and unpredictable inflammatory attacks that can be painful, debilitating, and life-threatening. About 1 in 50,000 people worldwide have the condition, Intellia said.

The FDA granted lonvo-z Regenerative Medicine Advanced Therapy designation, which allows the rolling submission format and gives the agency the opportunity to expedite its review. Intellia said it expects to complete the full BLA submission in the second half of 2026. If the filing is accepted, the FDA will determine whether to grant priority review and set a target action date. Intellia plans a commercial launch in the first half of 2027 if approval is granted.

Casgevy, a Vertex Pharmaceuticals $VRTX product, holds the distinction of being the sole CRISPR-based therapy currently on the U.S. market — but it relies on an ex vivo approach in which a patient's cells are extracted, edited in a laboratory setting, and then returned to the body, according to CNBC. If cleared, lonvo-z would be the only approved in vivo CRISPR therapy.

"If approved, lonvo-z will become the world's first in vivo CRISPR-based gene editing therapy," Intellia CEO John Leonard said in a statement.

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