The FDA last October paused Intellia Therapeutics’ late-stage CRISPR studies after detecting life-threatening enzyme elevations in one patient, who died a few days later.
Intellia Therapeutics can now freely move ahead with the development of its investigational CRISPR gene therapy after the FDA on Monday released the second of two studies that had previously been under clinical hold.
“The update sets the stage for substantial upside” potential, analysts at William Blair told investors in a Monday note. Without the regulatory overhang, the firm expects Intellia to be able to restart the program “quickly,” though no specific timeline has been given.
William Blair said that the risk-benefit profile for the therapy, nexiguran ziclumeran or nex-z, appears to be “attractive” with severe liver toxicity only occurring in a small amount of patients in the MAGNITUDE trial. The risk is manageable through enhanced monitoring and risk mitigation strategies, they continued.
Nex-z is in late-stage testing for transthyretin amyloidosis with cardiomyopathy (ATTR-CM). In late October 2025, the FDA froze both the Phase 3 MAGNITUDE and MAGNITUDE-2 trials after a patient in MAGNITUDE developed life-threatening elevations in liver enzymes. This patient died a few days later due to “complicating comorbidities,” Intellia CEO John Leonard said at the time.
In January this year, after agreeing to certain “modifications and mitigation measures,” including “enhanced safety monitoring of liver laboratory tests,” Intellia announced that the FDA released the hold on MAGNITUDE-2. On Monday, the biotech said that it had aligned with the regulator on similar safety mechanisms in the MAGNITUDE trial and noted that it will also implement short-term steroid interventions for patients who show elevated liver enzyme levels.
MAGNITUDE will also now exclude patients with a recent history of cardiovascular instability and those with ejection fraction lower than 25%, indicative of underlying issues that could increase the risk of more serious complications.
With both MAGNITUDE and MAGNITUDE-2 permitted to progress, “our attention now turns to completing enrollment in both ongoing trials,” Leonard said in a prepared statement on Monday. “We are very pleased to have aligned with the FDA on the path forward.”
Nex-z is a CRISPR-edited gene therapy that deactivates the TTR gene, which in turn lowers the overall expression of the transthyretin protein. In ATTR-CM, misfolded transthyretin clump together and accumulate in various tissues across the body, including in nerves and in the heart.
Intellia is advancing nex-z in partnership with Regeneron, which in April 2016 fronted $75 million to collaborate on the gene therapy. The gene editing biotech is also eligible for “significant” milestone and royalty payments, though an exact figure hasn’t been specified.
In 2022, Intellia reported that a patient treated with nex-z developed “significant elevation in liver enzymes,” though at the time the biotech dismissed the episode as it resolved spontaneously. In May 2025, just months before the death, the biotech again reported one case of life-threatening liver toxicity. Analysts at BMO Capital Market brushed it off as a “non-concern” at the time.
Intellia’s shares rose more than 12% on Monday to $15.44 apiece.
