Intellia ties its worst liver signals to a single HLA allele

Intellia Therapeutics reported on 6 August 2026 that a genomic analysis of more than 600 patient samples from its nexiguran ziclumeran (nex-z) trials found the highest liver transaminase elevations in patients carrying one specific human leukocyte antigen (HLA) allele. Chief executive John Leonard told BioSpace that each of the five highest elevations observed after dosing occurred in a carrier, while a strong majority of carriers showed no concerning increase. The company has not named the allele publicly.

nex-z is an in vivo CRISPR therapy that inactivates the TTR gene in the liver to stop production of transthyretin. The FDA placed the programme on clinical hold in October 2025 after life-threatening liver enzyme elevations; a patient died in November 2025; the hold was lifted in March 2026 once the agency accepted an enhanced safety-monitoring strategy.

Intellia will now give HLA genotyping results to investigators and to patients already enrolled or entering screening in MAGNITUDE and MAGNITUDE-2, its Phase 3 trials in ATTR amyloidosis with cardiomyopathy and hereditary ATTR amyloidosis with polyneuropathy, and says it is engaging the FDA and other health authorities on the finding.