Intellia Pauses Two CRISPR Trials After Severe Liver Toxicity Hospitalizes Patient

Intellia Therapeutics has temporarily paused enrollment and dosing in two Phase III clinical trials of its CRISPR-based drug for transthyretin amyloidosis after a patient in his 80s was hospitalized with a severe, potentially life-threatening spike in liver enzymes and bilirubin, signaling serious liver toxicity1.

The patient received the experimental therapy (codename nexiguran ziclumeran or nex-z) on September 30 and required hospitalization; this is the second time Intellia has reported such an incident since May 2025, though the previous case did not result in hospitalization1.

The trials involve over 650 patients in one study for the cardiomyopathy form of transthyretin amyloidosis and 47 patients in another for the polyneuropathy form1.

The cause of the liver toxicity remains unknown; Intellia suspects it may be related to the gene editing process itself rather than the delivery vehicle, but is investigating further1.

Intellia’s stock fell nearly 50% following the announcement, reflecting investor concerns about the future of its lead gene-editing programs14.

These safety events complicate Intellia’s prospects, as the diseases targeted already have effective therapeutic alternatives, raising the bar for risk tolerance in continued development3.

Sources:

1. https://www.biopharmadive.com/news/intellia-crispr-pause-transthyretin-amyloidosis-trials-liver-safety/803853/

3. https://www.statnews.com/2025/10/27/intellia-therapeutics-crispr-impact/

4. https://pharmaphorum.com/news/crispr-biotech-intellia-plummets-trial-paused-safety