FDA puts clinical hold on Intellia CRISPR therapy trials

The U.S. FDA has placed a clinical hold on a pair of phase 3 trials for Intellia Therapeutics’ in vivo CRISPR-based gene editing therapy, following a report of raised liver enzymes.

The agency verbally informed Intellia that it has placed a clinical hold on the investigational new drug applications for the MAGNITUDE and MAGNITUDE-2 phase 3 clinical trials for nexiguran ziclumeran (nex-z), the company revealed in an SEC filing. The FDA says it will provide a formal clinical hold letter in the next 30 days.

Earlier this week, Intellia had temporarily paused patient dosing and screening for the two trials of nex-z for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN). The decision came after a report of Grade 4 liver transaminases and increased total bilirubin in a patient who was dosed with nex-z in the MAGNITUDE trial on September 30, 2025, meeting the trial’s protocol-defined pausing criteria. The patient was hospitalized, is being closely monitored and is receiving medical intervention.

Hereditary ATTRv amyloidosis occurs when a person is born with mutations in the transthyretin (TTR) gene, which causes the liver to produce structurally abnormal TTR protein with a propensity to misfold. These damaged proteins build up as amyloid in the body, causing serious complications in multiple tissues, including the heart, nerves and digestive system. 

Based on Nobel Prize-winning CRISPR/Cas9 gene editing technology, nex-z is designed to inactivate the TTR gene that encodes for the TTR protein. Development and commercialization of the one-time treatment is led by Intellia as part of a multi-target collaboration inked with Regeneron back in 2016. Per the deal, Regeneron paid Intellia $75 million upfront for the exclusive rights to discover and develop CRISPR-based products against up to 10 targets.