FDA Lifts Clinical Hold on Intellia's MAGNITUDE-2 Trial for ATTRv-PN

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 (nex-z) for patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). Intellia Therapeutics announced on January 27, 2026, that the company plans to resume patient enrollment and dosing in the trial.

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.

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 updated protocol implies a focus on improving risk mitigation and data comprehension. The safety incidents that triggered the hold were uncommon, with two Grade 4/5 liver incidents, one of which was fatal, occurring in about 450 treated patients, accounting for less than 0.5% of the group.

MAGNITUDE-2 is a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of nex-z in 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. Enrollment in the study is expected to be completed in the second half of 2026.

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.

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. 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 and an Orphan Drug Designation 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.

In fourth-quarter 2025 financial results, Intellia reported a loss of 83 cents per share, narrower than the consensus estimate of a loss of 99 cents. The company reported revenues of $23 million for the fourth quarter of 2025, beating the consensus estimate of $12 million. Total revenues surged 73.8% on a year-over-year basis, driven by cost reimbursements related to the company's collaboration with Regeneron Pharmaceuticals and $9 million in revenues recognized from the termination of its license and collaboration agreement with SparingVision SAS.

As of Dec. 31, 2025, Intellia had cash, cash equivalents and marketable securities worth $605.1 million compared with $669.9 million as of Sept. 30, 2025. The company expects this cash balance to fund its ongoing operations into the second half of 2027 and the anticipated first commercial launch of its pipeline candidate, lonvo-z, which is being studied for hereditary angioedema (HAE).