Key Takeaways
- Intellia Therapeutics pauses Phase 3 trials after patient develops severe liver reaction
- Grade 4 liver toxicity reported in one participant dosed with CRISPR therapy nex-z
- Over 450 patients already treated across both MAGNITUDE trials
- Company consulting regulators and experts to determine next steps
Intellia Therapeutics has temporarily halted patient dosing and screening in its Phase 3 MAGNITUDE trials for nex-z, a CRISPR-based gene therapy. The pause follows a serious safety event where one participant developed severe liver complications.
Serious Liver Reaction Triggers Protocol Pause
A patient in the MAGNITUDE trial who received the therapy on September 30 developed Grade 4 liver transaminase elevations and increased total bilirubin. The adverse event, reported on October 24, met the study’s criteria for immediate suspension. The affected patient has been hospitalized and is receiving treatment under close medical supervision.
Company Response and 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,” stated 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.”
Intellia is currently consulting with medical experts and evaluating additional risk mitigation measures before proceeding.
Trial Impact and Patient Numbers
The MAGNITUDE trial has enrolled more than 650 patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), while MAGNITUDE-2 has recruited 47 patients with polyneuropathy (ATTR-PN). The company estimates that over 450 patients have already received the nex-z treatment across both studies.
About Nex-z CRISPR Therapy
Nex-z represents a groundbreaking approach as a potential one-time treatment for both ATTR-CM and ATTR-PN. The therapy uses CRISPR/Cas9 gene editing to permanently disable the TTR gene responsible for producing toxic transthyretin proteins. Earlier clinical data demonstrated deep and sustained TTR protein reductions following a single dose.
The therapy has received Orphan Drug and RMAT (Regenerative Medicine Advanced Therapy) designation from the US FDA, along with Orphan Drug status in Europe. Intellia leads development through its collaboration with Regeneron.
This development marks a significant moment for CRISPR-based medicines, as Intellia remains among the pioneering companies advancing systemic gene editing into late-stage clinical trials.
