The U.S. Food and Drug Administration (FDA) has lifted a clinical hold on Intellia Therapeutics’ MAGNITUDE-2 Phase III trial, which is testing the gene editing treatment nexiguran ziclumeran (nex-z) for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). The decision allows Intellia to resume patient enrollment in the study, following a pause that began in October 2025 after a serious adverse event in another trial.
Shares of Intellia rose by 10% to $15.39 in morning trading after the announcement.
Both the MAGNITUDE-2 and MAGNITUDE trials were halted last year when a participant in the MAGNITUDE trial developed severe liver complications after receiving nex-z, resulting in hospitalization and subsequent death in November 2025.
Analysts at William Blair commented on Tuesday that they continue to see potential for nex-z but cautioned that "this will be a no-news-is-good-news story as patient enrollment resumes" in MAGNITUDE-2. They also noted their support for new safety measures introduced by Intellia, stating these include enhanced monitoring of liver laboratory tests aimed at preventing further cases of liver damage associated with nex-z.
The FDA’s hold remains on the MAGNITUDE trial, which involves patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). “Engagement with the FDA is ongoing” regarding this trial, according to Intellia.
MAGNITUDE is enrolling 1,200 older patients with ATTR-CM, compared to just 60 younger patients enrolled in MAGNITUDE-2 for ATTRv-PN. William Blair analysts suggested that "we believe it is likely that the agency is being more cautious in the ATTR-CM indication, and that resumption of MAGNITUDE enrollment will require more stringent risk mitigation."
The investigational therapy nex-z uses CRISPR/Cas9 gene editing technology to disable the TTR gene responsible for producing misfolded proteins linked to ATTR. Early data from November 2025 indicated that nex-z could stabilize key markers of cardiomyopathy among ATTR-CM patients.
“We believe this bodes well for potential cardiac function and potential efficacy on cardiovascular outcomes,” William Blair wrote at the time those results were presented.
