Spiegazione semplice
Nex-z is given as one intravenous infusion. Tiny fat bubbles carry CRISPR machinery to the liver, where it disables the gene that makes the misfolding transthyretin protein. The idea is that a single treatment replaces medicines otherwise taken for the rest of a person's life. It is in Phase 3 trials, and it has had a serious safety event that its programme is still working through.
Approfondisci
Nexiguran ziclumeran is a lipid-nanoparticle-formulated CRISPR-Cas9 therapy targeting hepatic TTR, administered as a single intravenous infusion. Phase 1 data showed deep, durable serum transthyretin reduction. Phase 3 MAGNITUDE (ATTR-CM) and MAGNITUDE-2 (ATTR-PN) are under way. Developed by Intellia Therapeutics.
Safety events and the clinical hold
In late 2025 a MAGNITUDE participant — a man in his early eighties — developed grade 4 liver transaminase elevation and raised bilirubin following dosing, and subsequently died of liver dysfunction. Intellia voluntarily paused dosing and screening in both MAGNITUDE studies, and the FDA placed them on clinical hold. The hold on the MAGNITUDE Phase 3 trial in ATTR-CM was subsequently lifted.
The Atlas records this sequence in full because it is the field's most instructive safety case. A one-time, permanent, in vivo treatment cannot be withdrawn from a patient who reacts badly to it. That asymmetry is the central risk of the entire in vivo editing approach, and it is why regulators, sponsors and investigators treat these events with the gravity they do.
Sources
- New England Journal of Medicine (Gillmore et al.) · 2021
CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis ↗ - Intellia Therapeutics · 2025
Intellia provides update on MAGNITUDE clinical trials ↗