Intellia Therapeutics has paused dosing and screening in two global phase 3 trials testing its CRISPR-based treatment for transthyretin amyloid cardiomyopathy (ATTR-CM) after a patient developed severe liver toxicity, according to a press release published recently by the company.
The company said the move follows predefined safety rules and reflects its commitment to patient protection while the event is investigated.
The patient, who has ATTR-CM, was hospitalized after developing grade 4 elevations in liver enzymes and high bilirubin roughly three weeks after receiving a single dose of the investigational therapy, known as nex-z. The reaction met the study’s criteria for a temporary hold. Intellia reported that the patient is receiving active treatment and is under close medical supervision.
More than 650 people with ATTR-CM have joined the phase 3 MAGNITUDE trial, and another 47 with transthyretin amyloid polyneuropathy (ATTR-PN) are enrolled in the sister MAGNITUDE-2 trial. About 450 participants across both studies are estimated to have received nex-z.
Read more about therapies for ATTR-CM
“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 Intellia President and Chief Executive Officer Dr. John Leonard.
The liver event occurred in a MAGNITUDE participant treated on Sept. 30, 2025. On Oct. 24, blood tests revealed sharply elevated liver enzymes and bilirubin, triggering an automatic halt to further dosing. Intellia is reviewing the event to determine whether the toxicity was linked to the treatment or other factors.
Nex-z is designed to permanently disable the TTR gene, which produces transthyretin protein that builds up and damages organs in people with ATTR-CM and ATTR-PN. Earlier studies showed that a single infusion produced deep and lasting reductions in the protein, raising hopes for a potential one-time treatment.
For patients, the pause means new enrollment and dosing are on hold while safety data are reviewed. Although the delay may slow progress, the step underscores strict safety standards in developing gene-editing therapies. Intellia emphasized transparency as it evaluates nex-z’s risk-benefit profile and continues advancing CRISPR-based treatments for rare diseases.
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