FDA lifts remaining hold on Intellia CRISPR-based gene editing trial

The U.S. FDA has removed the clinical hold on Intellia Therapeutics’ IND for the MAGNITUDE phase 3 clinical trial of nexiguran ziclumeran (nex-z) for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM).

In October 2025, the FDA had verbally informed Intellia that it had placed a clinical hold on the INDs for two trials — MAGNITUDE and MAGNITUDE-2 — for nex-z, an in vivo CRISPR-based gene editing therapy, after a patient in his early 80s with complicating comorbidities experienced Grade 4 liver transaminase elevations and increased total bilirubin. The patient, who was enrolled in the MAGNITUDE ATTR-CM clinical trial, later passed away.

Earlier this year, the agency removed the clinical hold on the IND for Intellia’s MAGNITUDE-2 phase 3 trial of nex-z for patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).

Now, Intellia says it has aligned with the FDA on mitigation measures for MAGNITUDE and MAGNITUDE-2 that include enhanced monitoring of liver laboratory tests, guidance for short-term steroid treatment if elevated liver transaminases are observed in the initial period following dosing and the exclusion of patients with certain liver abnormalities.

Based on Nobel Prize-winning CRISPR/Cas9 gene editing technology, nex-z has the potential to become the first one-time treatment for ATTR-CM and/or hereditary ATTRv-PN. Nex-z is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein.