FDA Lifts Clinical Hold on Intellia’s Phase 3 CRISPR Therapy Trial

March 02, 2026 —

The U.S. FDA has lifted the clinical hold on Magnitude, the phase 3 trial evaluating nexiguran ziclumeran (nex-z), Intellia Therapeutics’ CRISPR-based gene therapy developed in partnership with Regeneron Pharmaceuticals for transthyretin amyloidosis with cardiomyopathy (ATTR-CM).

The hold was originally imposed last October after a patient in the Magnitude study experienced elevated liver enzymes that later led to death. A related phase 3 study, Magnitude-2, evaluating nex-z in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), had previously been cleared in January.

Under the updated protocol, Intellia will implement additional safeguards to enhance patient safety. The company will exclude patients with certain pre-existing liver conditions, those with a heart ejection fraction below 25%, and individuals with a recent history of cardiovascular instability. In addition, liver enzyme monitoring will be intensified throughout the study, and investigators will receive guidance on the use of short-term steroid management for patients who develop hepatic adverse events.

Company leadership stated that the revised measures are designed to enhance patient safety while allowing continued investigation of nex-z across a broad ATTR-CM population.

Analysts described the safety modifications as modest and suggested the clinical timeline is unlikely to face major disruption. However, uncertainty remains regarding the root cause of the liver toxicity, which may influence physician and patient adoption pending further clarity.

Nex-z is designed as a one-time CRISPR-based therapy delivered via lipid nanoparticles to disrupt the transthyretin (TTR) gene, reducing production of the pathogenic protein responsible for ATTR-CM and ATTRv-PN.