FDA verbally informed Intellia Therapeutics of a clinical hold on its two Phase 3 trials, MAGNITUDE and MAGNITUDE‑2, on October 29, 2025. The company had already voluntarily paused patient dosing and screening on October 27 after a serious liver‑related adverse event was reported on September 30.
The trials evaluate nex‑z (NTLA‑2001), a CRISPR‑based gene‑editing therapy developed with Regeneron, for transthyretin amyloidosis with cardiomyopathy (ATTR‑CM) and polyneuropathy (ATTR‑PN). Nex‑z has received the FDA’s Regenerative Medicine Advanced Therapy designation.
The hold was triggered by a Grade 4 elevation of liver transaminases and total bilirubin in a patient, an event that meets the Hy’s Law definition of potential drug‑induced liver injury. This is not the first liver‑related safety signal; a similar Grade 4 elevation was reported in May 2025 and earlier liver enzyme elevations were noted in a Phase 1 study in August 2022.
The pause suspends dosing and screening for both studies. As of October 27, more than 650 patients were enrolled in MAGNITUDE and 47 in MAGNITUDE‑2, with over 450 patients having received nex‑z across the two trials. Intellia will work with the FDA to address the safety concerns and resume enrollment once the hold is lifted.
Nex‑z aims to provide a one‑time curative treatment for ATTR, distinguishing it from daily or periodic therapies such as tafamidis, acoramidis, and vutrisiran. The clinical hold delays Intellia’s development timeline and underscores the regulatory scrutiny surrounding gene‑editing therapies.
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