Intellia Therapeutics has temporarily paused dosing in two Phase III trials testing its experimental CRISPR-based gene-editing therapy nexiguran ziclumeran (nex-z) after a patient was hospitalised with severe liver toxicity. Shares of the biotech fell more than 46% Monday following the disclosure, which reignites long-standing concerns over liver safety for gene-editing medicines.The pause affects Intellia's Phase III MAGNITUDE and MAGNITUDE-2 studies, which are evaluating nex-z for transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN), respectively.The company said the event involved a patient dosed in the MAGNITUDE trial on Sept. 30 who later developed Grade 4 elevations in liver transaminases and increased total bilirubin, triggering the trials' protocol-defined stopping rule. "In line with our commitment to patient safety, we have taken immediate action to temporarily pause enrollment in MAGNITUDE and MAGNITUDE-2 as we investigate this recent event," said CEO John Leonard.Nex-z, formerly known as NTLA-2001, is designed as a one-time treatment that knocks out the TTR gene, halting production of the transthyretin (TTR) protein that drives the disease. Last month, Intellia reported Phase I data showing that one dose of nex-z in ATTR-PN patients led to mean TTR reductions of at least 90% from baseline sustained out to three years.But safety has remained a key variable: in May, the company revealed that one participant had developed a serious, but symptom-free liver side effect, which appeared to resolve without intervention. At the time, Cantor Fitzgerald's Rick Bienkowski said it wasn't "quite time to panic yet."Liver damage has been an issue for companies pursuing in vivo CRISPR editing, which typically targets the liver. In 2024, Verve Therapeutics paused its cholesterol-lowering programme VERVE-101 following a similar signal. The company, recently acquired by Eli Lilly for $1.3 billion, has since advanced a second PCSK9-targeting base editor, VERVE-102, that demonstrated a clean safety profile in early testing."As we focus on ensuring the health of this patient, we also are engaging with regulatory authorities and other stakeholders globally to develop a strategy to resume enrollment as soon as appropriate," Leonard said. As of Monday, Intellia said it had enrolled more than 650 patients in the MAGNITUDE and 47 in MAGNITUDE-2, with roughly 450 participants across both trials already treated with nex-z.