Intellia Therapeutics announces FDA lift of clinical hold on MAGNITUDE-2 trial

Intellia Therapeutics (NTLA) announced that the U.S. Food and Drug Administration has removed the clinical hold on the Investigational New Drug application for the MAGNITUDE-2 Phase 3 clinical trial of nexiguran ziclumeran for patients with hereditary transthyretin amyloidosis with polyneuropathy. Intellia’s engagement with FDA is ongoing regarding the clinical hold on the IND for the MAGNITUDE Phase 3 clinical trial of nex-z for patients with transthyretin amyloidosis with cardiomyopathy. The company plans to provide an update once alignment has been achieved on the path forward for this program. 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 certain study modifications and mitigation measures related to MAGNITUDE-2 that include enhanced safety monitoring of liver laboratory tests. The company is engaged with clinical trial investigators, ethics committees, international regulatory authorities and other stakeholders to resume enrollment activities in MAGNITUDE-2 as quickly as possible. MAGNITUDE-2 is a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of nex-z in patients with ATTRv-PN. As part of the protocol amendment, Intellia has increased the trial’s target enrollment from approximately 50 patients to approximately 60 patients with ATTRv-PN. The primary endpoints of the study are a change in modified neuropathy impairment score and a change in serum TTR levels. Adult patients with ATTRv-PN are randomized 1:1 to receive a single 55 mg infusion of nex-z or placebo.