Intellia identifies HLA allele linked to severe liver enzyme spikes in ATTR gene therapy

In November 2025, a patient died after receiving Intellia Therapeutics' investigational gene silencer for transthyretin amyloidosis, prompting a safety review of the company’s ATTR gene therapy program.

Intellia reported that a specific allele of the HLA gene was associated with the highest elevations in liver transaminases among treated patients. All five of the most extreme enzyme spikes occurred in individuals carrying this allele, although most carriers did not experience concerning liver enzyme increases.

The company plans to share the genotyping data with investigators and present the findings to the FDA and other health authorities, aiming to clarify the risk profile for patients with the allele.

Analysts noted that pinpointing the genetic factor could reduce overall platform risk and help preserve the therapeutic potential of Intellia's gene editing approach.