Intellia Therapeutics has announced a temporary pause in patient dosing and screening for its MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials of nexiguran ziclumeran (nex-z), aimed at treating transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN). This decision comes in response to a serious safety event reported on October 24, 2025, involving elevated liver transaminases and total bilirubin levels in a patient who had received the drug on September 30, which met the criteria for pausing as outlined in the trial’s protocol.
The affected patient is currently hospitalized and under close medical surveillance, prompting Intellia to confer with experts and engage with regulatory authorities to explore risk mitigation strategies. John Leonard, M.D., President and CEO of Intellia, emphasized the priority of patient safety in the company’s response, highlighting their commitment to ensuring the well-being of participants while preparing a plan to resume enrollment in the trials as soon as it is deemed safe.
Currently, over 650 patients are enrolled in the MAGNITUDE trial for ATTR-CM, and 47 in MAGNITUDE-2 for ATTR-PN, with more than 450 patients having received doses of nex-z. Intellia is collaborating with Regeneron Pharmaceuticals on this treatment, which utilizes CRISPR/Cas9 gene editing technology to aim for a one-time therapy capable of reducing the production of the transthyretin protein.
The company has scheduled a conference call for 8:30 a.m. ET today to provide further updates on this situation, which can be accessed via their corporate website or through designated phone lines for participants.
Nex-z represents a hopeful advance in treatment possibilities for patients suffering from ATTR-CM and ATTR-PN. Preliminary Phase 1 trial results demonstrated significant and sustained reductions in transthyretin levels, paving the way for innovations in how these challenging conditions may be managed in the future.