Intellia Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has removed the clinical hold on the Investigational New Drug application (IND) for the MAGNITUDE Phase 3 clinical trial of nexiguran ziclumeran (nex-z) for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The clinical holds on the INDs for MAGNITUDE and MAGNITUDE-2 were imposed by the FDA on October 29, 2025, following the observation of Grade 4 liver transaminases and increased total bilirubin in a patient who was dosed with nex-z in MAGNITUDE that met the trial's protocol-defined pausing criteria. The company has aligned with the FDA on mitigation measures for MAGNITUDE & MAGNITUDE andMAGNITUDE-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.ex-z is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein and is being investigated in MAGNITUDE and MagNITUDE-2, Phase 3 clinical trials in ATTR-CM and ATTRv-PN, respectively.
Interim Phase 1 clinical data showed the administration of nex-z led to consistent, deep and long-lasting TTR reduction.ex-z has received an Orphan Drug and RMAT Designation from the U.S. Foodand Drug Administration (FDA) and an Orphan Drug Designation (ODD) from the European Commission.
