Intellia pauses Phase 3 CRISPR trial as patient develops serious liver reaction to therapy called nex-z

Intellia Therapeutics has temporarily paused patient dosing and screening in its Phase 3 MAGNITUDE and MAGNITUDE-2 trials for nex-z, a CRISPR-based therapy for transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN). The suspension follows a severe safety event involving one participant.

Grade 4 liver toxicity triggered protocol pause

According to the company, a patient in the MAGNITUDE trial who was dosed on September 30 developed Grade 4 liver transaminase elevations and increased total bilirubin, reported on October 24. The incident met the protocol’s criteria for pausing the study. The patient has been hospitalized and is receiving treatment while under close monitoring.

Company prioritizes patient safety

“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,” CEO John Leonard, M.D., said in a statement. “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.”

Intellia is consulting experts and considering additional risk mitigation measures as it works through next steps.

Ongoing late stage studies impacted

Intellia Therapeutics providing an update said MAGNITUDE has enrolled more than 650 ATTR-CM patients to date, while 47 ATTR-PN patients have joined MAGNITUDE-2. The company estimates that over 450 patients have already been dosed with nex-z across both trials.

First-in-class one-time therapy

Nex-z uses CRISPR/Cas9 gene editing to permanently disable the TTR gene responsible for producing toxic transthyretin proteins. It is being developed as a potential one-time treatment for both ATTR-CM and ATTR-PN. Earlier clinical data showed deep and sustained TTR protein reductions after a single dose.

The therapy has received Orphan Drug and RMAT designation from the US Food and Drug Administration, along with Orphan Drug status in Europe. Intellia is leading development under a collaboration with Regeneron.

Advancing CRISPR-based medicines

Intellia is among the first companies to take systemic CRISPR gene editing into late stage clinical trials. The company remains focused on developing therapies addressing unmet medical needs while expanding delivery and editing platforms for future programs.