- Intellia Therapeutics has paused two Phase 3 clinical trials for its gene-editing therapy, nex-z, due to safety concerns.
- The halt was triggered after a patient experienced a Grade 4 liver-related adverse event and was hospitalized.
- Over 650 patients are enrolled in the MAGNITUDE trial, with more than 450 already dosed with the therapy.
- The company is investigating the event and working with global regulatory authorities to determine the next steps.
CRISPR Pioneer Halts Trials Over Patient Safety
CAMBRIDGE, Mass. – Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leader in CRISPR-based gene editing, has abruptly paused patient dosing and screening in its crucial MAGNITUDE and MAGNITUDE-2 Phase 3 trials. The decision impacts its promising therapy, nexiguran ziclumeran (nex-z), designed for patients with transthyretin amyloidosis (ATTR), a debilitating condition.
Immediate Action Following Hospitalization
The company took this drastic step after a patient dosed on September 30, 2025, developed Grade 4 liver transaminases and increased bilirubin, prompting hospitalization. This serious adverse event met the trial’s protocol-defined criteria for an immediate pause. Intellia confirmed the patient is being closely monitored and is receiving medical intervention.
“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,” stated Intellia President and CEO John Leonard, M.D. “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.”
Trials Impacted a Large Patient Pool
The pause raises significant concerns, given the large number of participants involved. As of the announcement, more than 650 patients with ATTR-CM are enrolled in the MAGNITUDE study, and another 47 patients with ATTR-PN are in the MAGNITUDE-2 trial. The company estimates that over 450 of these individuals have already been treated with nex-z, highlighting the urgency of the investigation.
Future of a Landmark Therapy in Question
Nex-z, developed using Nobel Prize-winning CRISPR/Cas9 technology, held the potential to be the first one-time treatment for ATTR amyloidosis. It is designed to permanently inactivate the gene responsible for the disease. The therapy had already received Orphan Drug Designation from both the U.S. Food and Drug Administration (FDA) and the European Commission, underscoring its potential importance.
Intellia is leading the development and commercialization of nex-z as part of a major collaboration with Regeneron Pharmaceuticals, Inc. The company has already hosted a conference call to address the concerns of investors and the public. The path forward for the trials now depends on the outcome of the investigation and discussions with regulatory bodies worldwide.