The FDA is freeing Intellia Therapeutics’ CRISPR therapy from one of two clinical holds, allowing a phase 3 study to resume after a grade 4 liver event and subsequent patient death was reported in the sister study.
The biotech’s stock is up 12% since yesterday, rising from $13.95 per share to $15.66 by 10:30 a.m. ET today.
William Blair analysts called the hold lift “clearly positive,” demonstrating Intellia’s ability to work with the FDA on risk-mitigation measures to restart enrollment for the trial, which the biotech plans to resume as quickly as possible.
Last fall, the FDA placed clinical holds on Intellia’s Magnitude and Magnitude-2 studies, which are evaluating the company’s experimental CRISPR therapy in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), respectively. Both diseases impact heart function.
The hold followed Intellia’s voluntary pause in response to a grade 4 liver event—a case of Hy’s Law—in the ATTR-CM trial. Shortly after the regulatory hold was implemented, Intellia disclosed that the impacted patient had died.
While the patient had several comorbidities, the reported cause of death was septic shock, indicating that that the liver enzyme elevation alone was unlikely to have been fatal. Intellia has said that the liver injury and enzyme elevations were likely due to its treatment, called nexiguran ziclumeran (nex-z), a CRISPR therapy designed to inactivate the TTR gene.
Now, Intellia has implemented new risk-mitigation procedures designed to prevent dosing in potentially at-risk patients in the ATTRv-PN study, according to the William Blair analysts. Measures include enhanced safety monitoring of liver lab tests and boosting target enrollment from 50 patients to 60.
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Analysts now await updates on the Magnitude study in ATTR-CM, a condition that more commonly impacts the elderly, making the patient population automatically more at risk compared to the ATTRv-PN population. The study has already recruited more than 650 patients of an expected 1,200. Both factors are likely leading to higher scrutiny for Magnitude than Magnitude-2.
Intellia’s nex-z therapy has secured both orphan drug and regenerative medicine advanced therapy tags from the FDA. The asset is one of the biotech’s most advanced clinical candidates, alongside lonvoguran ziclumeran, which is being tested out in hereditary angioedema (HAE).
“We continue to believe in the efficacy of Intellia’s platform, and 2026 will be a major year for the promising HAE program, but safety events from nex-z have been and will continue to be a stock overhang until further regulatory clarity is gained on resumption of Magnitude and as investors gain comfort with new risk-mitigation strategies, in our view,” William Blair analysts wrote Jan. 27.