A patient has died in Intellia Therapeutics' CRISPR/Cas9 gene editing clinical trials for its candidate treatment for transthyretin (ATTR) amyloidosis with cardiomyopathy (ATTR-CM) and/or polyneuropathy (ATTR-PN), nexiguran ziclumeran (nex-z).
The patient was hospitalised with elevated liver enzyme levels in late October, having been dosed with nex-z on September 30th.
Intellia immediately paused the trial and the FDA put a clinical hold on both trials shortly after receiving the safety signal.
Both studies remain on hold as the company works to understand the liver-related issues seen in the trials and develop a risk-mitigation plan.
The patient died last Wednesday night, with the company providing an update after the market closed on Thursday.
Intellia CEO John Leonard said on a call with investors that the patient was in his early 80s and had bilirubin and ALT that were two and three times the upper limit of normal.
"We were deeply saddened to learn that the patient who experienced Grade 4 liver transaminase elevations and increased total bilirubin following a dose of nex-z in the MAGNITUDE Phase III clinical trial, as reported on October 27, 2025, passed away," said Leonard in a statement.
“We have been advised by the treating physician that this is a case with complicating comorbidities and it is being further evaluated."
"We are working with clinical investigators and external experts to better understand the liver-related events that have been observed within MAGNITUDE and to develop our risk mitigation plan.”
It is unclear when the trials will resume.
Though dosing of the one-time therapy is paused, Intellia is continuing to monitor patients who have already received the treatment.
Nex-z
Nex-z is an investigational in vivo CRISPR-based therapy designed to inactivate the TTR gene in the liver, thereby preventing the production of transthyretin (TTR) protein.
It has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis with cardiomyopathy (ATTR-CM) and/or polyneuropathy (ATTR-PN).
Nex-z offers the possibility of halting and reversing disease by driving a deep, consistent and potentially lifelong reduction in TTR protein after a single dose.
It is currently being investigated in MAGNITUDE and MAGNITUDE-2, Phase III clinical trials in ATTR-CM and ATTR-PN, respectively.
Interim Phase I clinical data showed the administration of nex-z led to consistent, deep and long-lasting TTR reduction.
Nex-z has received an Orphan Drug and RMAT Designation from the FDA and an Orphan Drug Designation (ODD) from the European Commission.