Intellia Therapeutics Provides Update on Phase 3 MAGNITUDE Study; Reports Grade 4 Liver Enzyme Elevation in One Patient
Cambridge, MA, May 29, 2025 – Intellia Therapeutics, a leading clinical-stage genome editing company, today disclosed that one patient in its pivotal Phase 3 MAGNITUDE study of nex-z, its gene editing treatment for transthyretin amyloid (ATTR) cardiomyopathy, experienced a serious case of elevated liver enzymes.
The patient with ATTR cardiomyopathy had Grade 4 liver enzyme elevations based on lab tests. Importantly, the patient remained asymptomatic, and the case appears “to be resolving without hospitalization or medical intervention,” as reported by the company in an SEC filing. Intellia’s shares experienced a decline following the disclosure.
Intellia’s nex-z gene editing therapy is being evaluated for ATTR cardiomyopathy, a progressive and rare heart condition caused by the buildup of aberrant proteins. While gene editing studies are closely monitored for liver toxicities, Intellia has observed mostly mild cases to date. The company previously reported one other asymptomatic case of Grade 4 liver enzyme elevations in a study of nex-z for another form of transthyretin amyloidosis affecting peripheral nerves.
The MAGNITUDE study aims to enroll 765 patients, with approximately 365 patients enrolled so far and over 200 patients dosed. Intellia anticipates completing enrollment in early 2027. Nex-z is an investigational CRISPR-based therapy designed to inactivate the TTR gene in the liver, reducing the abnormal protein buildup that causes ATTR amyloidosis. It consists of a proprietary lipid nanoparticle (LNP) delivery system with liver tropism, carrying a single guide RNA (sgRNA) that targets human TTR and a human-codon–optimized mRNA sequence of Streptococcus pyogenes Cas9 protein.
The disclosure comes amidst increased scrutiny on genetic medicines and the recent approval of new ATTR treatments, including BridgeBio’s Attruby and Alnylam’s Amvuttra. Intellia remains committed to advancing the MAGNITUDE study and its broader gene editing pipeline.
Source:
https://endpts.com/intellia-reports-case-of-liver-toxicity-in-attr-gene-editing-study/
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