Two of Intellia Therapeutics’ clinical trials that had been on hold since October 2025 have now been released by the FDA. According to The New England Journal of Medicine, the Agency issued the holds due to reports of severe liver toxicity leading to death.
The Magnitude study was originally known as NTLA-2001. It is a one-time gene-editing therapy developed to treat amyloidosis (pronounced am-uh-loi-DO-sis). The protein, known as amyloid, accumulates and affects major organs. Magnitude and Magnitude-2 trials were halted by the FDA when a patient was reported to have high levels of liver enzymes that eventually led to the patient’s death.
Magnitude Phase 3 trial
The FDA has now lifted the second hold, the Magnitude phase 3 trial that was investigating nexiguran ziclumeran (nex-z) in patients with ATTR-CM. If the protein becomes misshapen it causes clumps to occur in the gene. These clumps damage the heart and various other organs.
New Safety Measures
Currently, each new release contains warnings by Intellia that patients with the following will be excluded from the Magnitude trials:
- liver issues
- a heart ejection fraction (EF) of under twenty-five percent (an EF of 50% to 70%EF is normal)
- recent history of cardiovascular instability
Additional Safety Issues
Other safety issues were announced, such as the degree of monitoring of liver enzymes and providing guidance on steroid therapy to patients experiencing side effects that are potentially dangerous.
Intellia President and CEO Dr. John Leonard was quoted in a recent news release commenting that he was pleased the company was aligned with the FDA in improving patient safety.
Since the FDA released the holds, Intellia is again focusing on the investigation of nex-z, a one-time therapy for ATTR-PM and ATTR-CM using CRISPR gene editing to disrupt the gene that makes the protein transthyretin.
About Transthyretin (TTR)
The TTR protein transports thyroxine, a thyroid hormone and retinol-binding protein that carries vitamin A through cerebrospinal fluid and blood. When it becomes unstable and misfolds, it deposits in tissues as amyloid fibrils leading to amyloidosis.
Nex-z Is a one-time Therapy
Nex-z was designed as a therapy for ATTR-PN and ATTR-CM using CRISPR gene editing to disrupt the gene that is responsible for making the protein transthyretin.
Sarepta Therapeutics dealt with safety issues last year involving muscular dystrophy therapies, including Elevidys, that caused 3 liver-related patient deaths. The cause of the liver toxicity is still unknown. Until patients and doctors see some clarity, it is believed they will continue to adopt a cautious approach.
