Rare Daily Staff
Intellia Therapeutics said a patient in a phase 3 clinical trial of its experimental CRISPR gene-editing therapy has died.
Last month, Intellia paused dosing and screening in its phase 3 studies of its experimental therapy, nex-z, for patients with transthyretin amyloidosis with cardiomyopathy and polyneuropathy, following a report of a patient who experienced a severe elevation of liver enzymes after receiving the therapy. The company previously reported that the patient was hospitalized, was being closely monitored, and was receiving medical intervention.
The company announced the death in the release of its quarterly earnings.
“We have been advised by the treating physician that this is a case with complicating comorbidities, and it is being further evaluated,” said John Leonard, CEO of Intellia. “As we await the FDA’s clinical hold letter, we are working with clinical investigators and external experts to better understand the liver-related events that have been observed within MAGNITUDE, and to develop our risk mitigation plan.”
On Oct. 29, 2025, the U.S. Food and Drug Administration placed a clinical hold on the investigational new drug applications for the MAGNITUDE and MAGNITUDE-2 phase 3 clinical trials for patients with ATTR amyloidosis with cardiomyopathy and hereditary ATTR amyloidosis with polyneuropathy.
More than 650 patients with ATTR-CM are currently enrolled in MAGNITUDE, and 47 patients with ATTRv-PN are enrolled in MAGNITUDE-2. Intellia said to date, Grade 4 liver transaminase elevations have been reported in less than 1 percent of all patients enrolled in MAGNITUDE, and no Grade 4 liver transaminase elevations have been reported in MAGNITUDE-2.
“We continue to believe in nex-z’s potential to address important unmet needs for patients with ATTR amyloidosis,” Leonard said.
Transthyretin amyloidosis, or ATTR amyloidosis, is a rare, progressive, and fatal disease. It causes the liver to produce structurally abnormal transthyretin protein, which has a propensity to misfold. These damaged proteins accumulate as amyloid in the body, leading to severe complications in multiple tissues, including the heart, nerves, and digestive system. ATTR can lead to nerve damage or cardiomyopathy (ATTR-CM), which may result in heart failure.
Nex-z, a CRISPR-Cas9 gene-editing therapy, has the potential to become the first one-time treatment for transthyretin amyloidosis. It is designed to inactivate the TTR gene that encodes the transthyretin protein.
Interim phase 1clinical data showed that administration of nex-z led to consistent, deep, and long-lasting TTR reduction. Nex-z has received orphan drug and RMAT designations from the U.S. Food and Drug Administration, and orphan drug designation from the European Commission.
Intellia leads the development and commercialization of nex-z as part of a multi-target discovery, development, and commercialization collaboration with Regeneron Pharmaceuticals.
Photo: John Leonard, CEO of Intellia Therapeutics
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