Nexiguran ziclumeran for ATTR-CM
Fact-checked by What is nexiguran ziclumeran for ATTR-CM?
Nexiguran ziclumeran, or nex-z (also called NTLA-2001), is an experimental gene-editing therapy being tested as a treatment for transthyretin amyloidosis with cardiomyopathy (ATTR-CM).
ATTR-CM is a type of heart disease that occurs when the transthyretin protein folds abnormally and accumulates in the body, especially the heart. This damages tissues and can lead to symptoms such as heart failure.
Nex-z aims to lower transthyretin levels by silencing the TTR gene, which contains the template that cells use to manufacture the protein. It uses CRISPR/Cas9 gene-editing technology to permanently inactivate TTR in liver cells, where most transthyretin production occurs. This is expected to reduce levels of toxic protein clumps and slow disease progression for people with both hereditary and age-related (wild-type) forms of the disease.
The therapy, being developed by Intellia Therapeutics and Regeneron Pharmaceuticals, is delivered as a one-time intravenous (into-the-vein) infusion. It is now in Phase 3 clinical trials for ATTR-CM. It is also being tested for people with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN), in which transthyretin buildup primarily affects nerves.
In the U.S., nex-z has orphan drug status and regenerative medicine advanced therapy status — designations intended to facilitate the development and regulatory review of medications. Regulators in the European Union have also granted nex-z orphan drug status as a rare disease treatment.
Therapy snapshot
| Treatment name | Nexiguran ziclumeran |
| Administration | One-time intravenous infusion |
| Clinical testing | In Phase 3 testing for ATTR-CM |
How will nexiguran ziclumeran be given in ATTR-CM?
In an ongoing Phase 3 clinical trial, people with ATTR-CM are receiving a single intravenous infusion of nex-z at a dose of 55 mg.
Nexiguran ziclumeran in ATTR-CM clinical trials
The Phase 3 MAGNITUDE trial (NCT06128629) is evaluating the safety and efficacy of nex-z in adults with ATTR-CM and mild to moderate heart failure. The approximately 1,200 participants will receive either a single infusion of nex-z (55 mg) or a placebo. The study’s main goal is to evaluate whether nex-z reduces the risk of serious cardiovascular events or cardiovascular-related death.
U.S. regulators put a temporary hold on MAGNITUDE in October 2025 after one trial participant who received nex-z developed severe liver damage and eventually died. This hold was lifted in March 2026 with new protocols for monitoring and treating liver problems in place.
A previous Phase 1 clinical trial (NCT04601051) tested the safety of nex-z in adults with ATTR-CM or hATTR-PN. All participants received a single intravenous infusion of the medication at varying doses. Results from the 36 participants with ATTR-CM showed that nex-z led to:
- about a 90% drop in blood transthyretin levels after one month that was sustained for as long as three years
- stabilization or improvements in heart damage biomarkers, exercise capacity, functional status, and measures of heart structure and function
- stabilizations or improvements in quality of life
- a 73% lower risk of death compared with an external group of ATTR-CM patients who did not receive disease-specific treatment
Participants from this study could enter a long-term follow-up trial (NCT05697861), which is tracking safety for as long as 15 years.
Nexiguran ziclumeran side effects
Among ATTR-CM participants in a Phase 1 trial, the most common side effects considered potentially related to nex-z treatment were:
- infusion-related reactions
- elevated liver enzymes, which could be a sign of liver damage
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