The clinical hold comes days after Intellia voluntarily paused enrollment and dosing in the same two studies.
The FDA has officially placed two of Intellia’s Phase III studies under clinical hold after the biotech reported earlier this week that one patient developed life-threatening liver side effects.
The regulatory freeze, disclosed in an SEC filing on Wednesday, applies to Intellia’s MAGNITUDE and MAGNITUDE-2 trials, which are evaluating the CRISPR-edited gene therapy nexiguran ziclumeran (nex-z) in transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN). The FDA has still only verbally communicated the hold but is expected to issue a formal letter in the next 30 days, Intellia said.
At $11.07 apiece, the biotech’s shares are down 15.6% in pre-market trading. Its previous closing price was $13.12.
Intellia first revealed the safety signal on Monday, announcing that one patient, enrolled in MAGNITUDE, developed elevations in liver transaminase and bilirubin concentrations, enough that it qualified as a grade 4 or life-threatening event. These side effects were documented on Sept. 30 and the patient was subsequently hospitalized and given medical attention.
The biotech on Monday voluntarily suspended screening and treatment in both MAGNTIUDE and MAGNITUDE-2, and at the time said that it was consulting experts to chart a path forward for nex-z, including the potential addition of risk mitigation mechanisms.
Nex-z had previously run into some toxicity troubles. In May, Intellia reported that another patient had similarly developed grade 4 liver enzyme elevations after receiving the gene therapy. The biotech did not pause the study at the time, and analysts largely swept the episode under the rug—BMO Capital Markets in a May 29 note called the safety signal a “non-concern.”
In August 2022 Intellia similarly reported “significant elevation in liver enzymes” in a Phase I study of nex-z, though the episode was asymptomatic and resolved after 28 days.
Intellia’s toxicity troubles add to the growing worry about the safety of gene therapies. Most prominent of which this year are the three deaths associated with Sarepta Therapeutics’ products: Two mortalities attributed to the Duchenne muscular dystrophy therapy Elevidys and one to an investigational asset for limb-girdle muscular dystrophy.
Deaths have also occurred in trials of Rocket Pharmaceuticals’ Danon disease asset and Capsida Biotherapeutics’ treatment for STXBP1-related epileptic encephalopathy disorders.
