FDA Halts Intellia's Gene Therapy Trials Following Severe Liver Toxicity

The U.S. Food and Drug Administration (FDA) has placed two of Intellia Therapeutics' Phase III studies on clinical hold following reports of life-threatening liver toxicity in a patient. The decision marks a significant setback for the biotech company and raises concerns about the safety profile of CRISPR-edited gene therapies.

Clinical Trials Suspended Amid Safety Concerns

Intellia's MAGNITUDE and MAGNITUDE-2 trials, evaluating the CRISPR-edited gene therapy nexiguran ziclumeran (nex-z) for transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN), have been officially suspended by the FDA. The regulatory action comes just days after Intellia voluntarily paused enrollment and dosing in these studies due to a patient developing severe liver side effects.

The affected patient, enrolled in the MAGNITUDE trial, experienced elevations in liver transaminase and bilirubin concentrations that qualified as a grade 4 or life-threatening event. The incident, documented on September 30, resulted in hospitalization and required medical intervention.

Previous Safety Signals and Industry-Wide Concerns

This is not the first time nex-z has encountered toxicity issues. In May, Intellia reported another patient developing grade 4 liver enzyme elevations after receiving the gene therapy. Additionally, in August 2022, the company noted "significant elevation in liver enzymes" in a Phase I study of nex-z, although that episode was asymptomatic and resolved after 28 days.

The recent developments at Intellia contribute to growing concerns about the safety of gene therapies across the pharmaceutical industry. Notable incidents include three deaths associated with Sarepta Therapeutics' products: two mortalities linked to the Duchenne muscular dystrophy therapy Elevidys and one to an investigational asset for limb-girdle muscular dystrophy. Fatal outcomes have also been reported in trials conducted by Rocket Pharmaceuticals for Danon disease and Capsida Biotherapeutics for STXBP1-related epileptic encephalopathy disorders.

Market Impact and Next Steps

The news has had a significant impact on Intellia's stock price, with shares down 15.6% in pre-market trading to $11.07, following a previous closing price of $13.12. The company is now in consultation with experts to determine the path forward for nex-z, including the potential addition of risk mitigation mechanisms.

Intellia anticipates receiving a formal letter from the FDA regarding the clinical hold within the next 30 days. The biotech industry and investors will be closely monitoring the situation, as it may have broader implications for the development and regulation of gene therapies.