FDA Lifts Hold On Intellia Therapeutics’ ATTR Polyneuropathy Trial, Cleared To Resume MAGNITUDE-2 Phase 3 Study Of Nex-Z

Intellia Therapeutics announced that the U.S. Food and Drug Administration has lifted the clinical hold on the Investigational New Drug application for MAGNITUDE-2, its Phase 3 trial of nexiguran ziclumeran (nex-z) in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). With the hold removed, the company is working with investigators, ethics committees, and regulators worldwide to restart patient enrollment as soon as possible.

Discussions with the FDA continue regarding the separate clinical hold on MAGNITUDE, the Phase 3 program evaluating nex-z in transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Intellia said it will provide further updates once regulatory alignment has been reached on the path forward for that study.

“We appreciate the FDA’s expeditious review of our submission and ongoing engagement and thank our study investigators and patients for their continued participation. With the clinical hold for MAGNITUDE-2 lifted, our team is focused on resuming patient enrollment as quickly as possible as we seek to advance this potential one-time treatment option for people living with ATTRv-PN,” said Intellia President and Chief Executive Officer John Leonard, M.D.

Both MAGNITUDE and MAGNITUDE-2 were placed on hold in October 2025 after a patient in the cardiomyopathy trial experienced severe liver laboratory abnormalities that met protocol-defined stopping rules. For MAGNITUDE-2, Intellia and the FDA have agreed on protocol changes and additional risk-mitigation measures, including enhanced monitoring of liver function tests, to support safe continuation of the study.

MAGNITUDE-2 is a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of a single infusion of nex-z in adults with ATTRv-PN. Under the amended protocol, target enrollment has been increased from about 50 to 60 patients, who will be randomized 1:1 to receive either a 55 mg dose of nex-z or placebo. The study’s primary endpoints include changes in neuropathy severity and serum transthyretin levels.