Intellia Therapeutics Announces FDA Lifts Clinical Hold on MAGNITUDE-2 Phase 3 Trial for ATTRv-PN
Intellia Therapeutics, Inc., a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today 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-2 Phase 3 clinical trial of nexiguran ziclumeran (nex-z) for patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).
“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.
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 (ATTR-CM). 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. For more information on MAGNITUDE-2 (NCT06672237),
About Nex-z
Based on Nobel Prize-winning CRISPR/Cas9 gene editing technology, nex-z has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis with cardiomyopathy (ATTR-CM) and/or hereditary ATTR with polyneuropathy (ATTRv-PN). Nex-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. Nex-z has received an Orphan Drug and RMAT Designation from the U.S. Food and Drug Administration (FDA) and an Orphan Drug Designation (ODD) from the European Commission. Intellia leads development and commercialization of nex-z as part of a multi-target discovery, development and commercialization collaboration with Regeneron Pharmaceuticals, Inc.
About Intellia Therapeutics
Intellia Therapeutics, Inc. (NASDAQ:NTLA) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. Since its inception, Intellia has focused on leveraging gene editing technology to develop novel, first-in-class medicines that address important unmet medical needs and advance the treatment paradigm for patients. Intellia’s deep scientific, technical and clinical development experience, along with its people, is helping set the standard for a new class of medicine. To harness the full potential of gene editing, Intellia continues to expand the capabilities of its CRISPR-based platform with novel editing and delivery technologies.
Source Link: https://ir.intelliatx.com/
