Safety Concern Halts Intellia’s Phase III CRISPR Gene Therapy Trials

CAMBRIDGE, MA — October 27, 2025 — Intellia Therapeutics announced today that it has placed a clinical hold on two Phase III studies of its lead CRISPR-based gene therapy candidate, nexiguran ziclumeran (nex-z), following a serious adverse event in a participant. The patient, enrolled in the MAGNITUDE trial for transthyretin amyloidosis with cardiomyopathy (ATTR-CM), experienced Grade 4 elevations in liver transaminase and bilirubin levels on September 30. Grade 4 adverse events are defined as life-threatening and requiring urgent medical attention. The patient has been hospitalized and is currently receiving medical care.

Trials Halted and Stock Drops

The clinical hold affects both the MAGNITUDE (ATTR-CM) and MAGNITUDE-2 (ATTR-PN, polyneuropathy) trials, which are assessing the efficacy of nex-z for transthyretin amyloidosis.

Intellia has informed regulatory authorities and is now working with experts to determine the best path forward for nex-z, including potential risk mitigation strategies. The news immediately impacted the company’s stock, with shares down nearly 43% before the market open on Monday.

Recurrent Liver Safety Signal

This is not the first time nex-z has been associated with liver enzyme elevations:

• May 2025: Intellia disclosed that another patient treated with nex-z experienced Grade 4 liver enzyme elevations. The company chose not to suspend dosing at that time, and analysts largely dismissed the signal, with BMO Capital Markets calling it a “non-concern.”
• August 2022: The therapy was linked to a “significant elevation in liver enzymes” during a Phase I ATTR-PN study. Though that event was asymptomatic and resolved on its own, Intellia amended the protocol to introduce a lower fixed-dose regimen.

Nex-z also known as NTLA-2001 is an investigational therapy developed under a partnership with Regeneron. It uses CRISPR gene editing technology and a lipid nanoparticle (LNP) delivery system to target and deactivate the TTR gene, which is responsible for producing the misfolded transthyretin protein that builds up in the nerves and heart of ATTR patients.