Intellia Pauses Phase 3 Clinical Trials of CRISPR-Based Therapy

Rare Daily Staff

Intellia Therapeutics said that it has paused patient dosing and screening in its phase 3 clinical trials of the experimental CRISPR therapy nex-z for patients with transthyretin amyloidosis with cardiomyopathy and polyneuropathy.

The decision follows a report on October 24, 2025, of Grade 4 liver transaminases and increased total bilirubin in a patient who received nex-z in the MAGNITUDE trial on September 30, 2025, meeting the trial’s protocol-defined pausing criteria. The patient was hospitalized, is being closely monitored, and is receiving medical intervention.

Transthyretin amyloidosis, or ATTR amyloidosis, is a rare, progressive, and fatal disease. It causes the liver to produce structurally abnormal transthyretin (TTR) protein, which has a propensity to misfold. These damaged proteins accumulate as amyloid in the body, leading to severe complications in multiple tissues, including the heart, nerves, and digestive system. ATTR can lead to nerve damage or cardiomyopathy (ATTR-CM), which may result in heart failure.

Nex-z, a CRISPR-Cas9 gene-editing therapy, has the potential to become the first one-time treatment for transthyretin amyloidosis. It is designed to inactivate the TTR gene that encodes for the transthyretin protein.

Interim phase 1 clinical data showed that administration of nex-z led to consistent, deep, and long-lasting TTR reduction. Nex-z has received Orphan Drug and RMAT designations from the U.S. Food and Drug Administration, and Orphan Drug designation from the European Commission.

Intellia leads the development and commercialization of nex-z as part of a multi-target discovery, development, and commercialization collaboration with Regeneron Pharmaceuticals.

As of today, more than 650 patients with ATTR-CM are enrolled in MAGNITUDE, and 47 patients with ATTR-PN are enrolled in MAGNITUDE-2. Over 450 of these patients are estimated to have received nex-z.

“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 CEO John Leonard. “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.”