FDA lifts hold on one of Intellia’s CRISPR-based gene editing trials

The U.S. FDA has removed the clinical hold on the IND for Intellia Therapeutics’ MAGNITUDE-2 phase 3 trial of nexiguran ziclumeran (nex-z) for patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).

In October 2025, the agency verbally informed Intellia that it has 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.

The patient — revealed in an investor call to be a male in his early 80s with complicating comorbidities — experienced Grade 4 liver transaminase elevations and increased total bilirubin following a dose of nex-z in the MAGNITUDE transthyretin amyloidosis clinical trial. In early November, the patient died.

Now, with the clinical hold for MAGNITUDE-2 lifted, Intellia says it is focused on resuming patient enrollment as quickly as possible. Intellia’s engagement with FDA remains ongoing regarding the clinical hold on the IND for the MAGNITUDE trial of nex-z for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The company plans to provide an update once alignment has been achieved on the path forward for this program.