After a patient safety signal and then death, the FDA in October 2025 placed holds on two of the company’s CRISPR programs for hereditary transthyretin amyloidosis.
The FDA has lifted a hold on one of Intellia Therapeutics’ gene editing programs, sending shares of the company bouncing upward in Tuesday morning trading.
The hold had been placed on the company’s application for the MAGNITUDE-2 Phase III trial for nexiguran ziclumeran, or nex-z, a gene editing treatment for patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), a rare genetic disease that causes nerve damage.
The company is resuming patient enrollment for MAGNITUDE-2, according to Intellia’s statement on Tuesday. Shares of Intellia rose 10% to $15.39 in morning trading.
MAGNITUDE-2, along with another trial called MAGNITUDE, had holds placed on them in October 2025 when a patient who had received nex-z in the MAGNITUDE trial developed life-threatening liver complications, which required hospitalization. That patient died in November 2025.
Analysts at William Blair said that they continue to believe in the potential of nex-z, but that “this will be a no-news-is-good-news story as patient enrollment resumes” in MAGNITUDE-2, according to a Tuesday investor note.
The analysts were also encouraged by new mitigation strategies that Intellia put in place, such as enhanced safety monitoring of liver laboratory tests, with the goal of preventing cases of patients experiencing liver damage from nex-z.
The hold for MAGNITUDE, which is testing nex-z in patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) remains. “Engagement with the FDA is ongoing” with respect to resolving the MAGNITUDE hold, Intellia said.
ATTR-CM affects more elderly patients, and MAGNITUDE is testing 1,200 patients, versus just 60 younger patients with ATTRv-PN in MAGNITUDE-2. For those reasons, “we believe it is likely that the agency is being more cautious in the ATTR-CM indication, and that resumption of MAGNITUDE enrollment will require more stringent risk mitigation,” according to the William Blair analysts.
Nex-z uses CRISPR/Cas9 gene editing technology to diable the TTR gene, which in ATTR is mutated and therefore yields a protein that misfolds and accumulates. Phase I data presented in November 2025 showed that nex-z could stabilize clinical endpoints of cardiomyopathy in patients with ATTR-CM.
“We believe this bodes well for potential cardiac function and potential efficacy on cardiovascular outcomes,” William Blair wrote in a note at the time of that data drop.
