Nexiguran ziclumeran (nex-z), an investigational CRISPR-Cas9 gene therapy for transthyretin amyloid cardiomyopathy (ATTR-CM), continues to demonstrate long-term efficacy in early-phase research, even as its phase III trials remain on hold due to a serious safety event, as reported on Med Page Today.
Key Findings from Phase I:
- In a 36-patient cohort, serum transthyretin (TTR) levels dropped by 87% from baseline and stayed suppressed for up to 36 months post-treatment.
- Clinical markers of disease progression, including NT-proBNP, troponin T, and 6-minute walk distance, remained stable over a median follow-up of 25.5 months.
- Most adverse events were mild and transient, such as infusion reactions and short-lived liver enzyme elevations.
Safety Update:
Phase III trials (MAGNITUDE and MAGNITUDE-2) were paused after a participant experienced severe liver toxicity and later died. Investigators are assessing whether the fatality was treatment-related and exploring mitigation strategies.
Expert Perspective:
Researchers remain optimistic about gene-editing’s potential in cardiovascular disease. Nex-z aims to permanently inactivate the TTR gene via a single IV infusion, offering a possible one-time treatment for ATTR—a progressive condition caused by misfolded TTR protein.
Next Steps:
While early data suggest durable biochemical and functional benefits, experts caution that randomized controlled trials are essential to confirm efficacy and safety before widespread adoption.
