FDA Places Clinical Hold on Intellia's Gene Therapy Studies Due to Liver Toxicity

The U.S. Food and Drug Administration (FDA) has officially placed two of Intellia Therapeutics' Phase III studies under clinical hold following reports of life-threatening liver side effects in a patient. This regulatory action comes just days after Intellia voluntarily paused enrollment and dosing in the same trials.

Safety Concerns Halt CRISPR Gene Therapy Trials

The clinical hold affects Intellia's MAGNITUDE and MAGNITUDE-2 trials, which are evaluating the CRISPR-edited gene therapy nexiguran ziclumeran (nex-z) in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN). The FDA's decision was disclosed in an SEC filing on Wednesday, with the agency expected to issue a formal letter within the next 30 days.

The safety signal that triggered this action was first revealed by Intellia on Monday. A patient enrolled in the MAGNITUDE study developed severe elevations in liver transaminase and bilirubin concentrations, qualifying as a grade 4 or life-threatening event. The incident occurred on September 30, resulting in the patient's hospitalization and subsequent medical attention.

Recurring Toxicity Issues and Market Impact

This is not the first time nex-z has faced toxicity concerns. In May, Intellia reported another patient developing grade 4 liver enzyme elevations after receiving the gene therapy. Despite this earlier incident, the study was not paused at that time, with some analysts dismissing the safety signal as a "non-concern."

The latest development has had a significant impact on Intellia's stock price. In pre-market trading, the biotech's shares fell 15.6% to $11.07, down from the previous closing price of $13.12.

Broader Implications for Gene Therapy Safety

Intellia's toxicity troubles contribute to growing concerns about the safety of gene therapies across the industry. This year has seen several high-profile safety issues, including three deaths associated with Sarepta Therapeutics' products: two attributed to the Duchenne muscular dystrophy therapy Elevidys and one to an investigational asset for limb-girdle muscular dystrophy.

Additional fatalities have been reported in trials of Rocket Pharmaceuticals' Danon disease asset and Capsida Biotherapeutics' treatment for STXBP1-related epileptic encephalopathy disorders. These incidents collectively underscore the potential risks associated with advanced genetic therapies and highlight the need for rigorous safety monitoring in clinical trials.