Nexiguran ziclumeran

A one-time IV infusion that uses CRISPR gene editing to permanently turn off the TTR gene in liver cells. If successful, patients would no longer need ongoing treatment.

Nexiguran ziclumeran uses CRISPR gene editing technology to permanently turn off the TTR gene in your liver cells. Instead of blocking the protein like other drugs, this treatment actually edits the DNA code that makes TTR, providing potentially permanent reduction of the toxic protein with a single infusion.

In the Phase 1 study of 36 people with the nerve form of hereditary ATTR (polyneuropathy), the most common side effects were infusion reactions (21 people), a temporary drop in the thyroid hormone thyroxine without thyroid disease (8) and headache (4)^[5]. In the Phase 3 MAGNITUDE trial, fewer than 1% of patients had grade 4 liver enzyme rises. One of them, who also had raised bilirubin, died on November 5, 2025; Intellia said the treating physician described a case with complicating comorbidities. The FDA placed both Phase 3 trials on clinical hold on October 29, 2025 and lifted the holds on January 27 and March 2, 2026, with closer liver-test monitoring, guidance on short-term steroid treatment and new exclusions. In August 2026 Intellia reported that the highest liver enzyme rises occurred in patients carrying one specific HLA allele, an immune-system gene type, and said it would give HLA genotyping results to trial investigators and patients.

Nexiguran ziclumeran is given as a single intravenous infusion (into a vein). Because it's a one-time gene editing treatment, patients receive just one dose, unlike other ATTR treatments that require ongoing injections or pills. It is available only in clinical trials.

Nexiguran ziclumeran is currently in phase 3 clinical trials for ATTR Amyloidosis and Wild-Type ATTR Cardiac Amyloidosis. It has not yet received FDA approval.

Nexiguran ziclumeran is a one-time gene editing therapy that uses CRISPR-Cas9 to permanently disable the TTR gene in liver cells. Unlike stabilizers (tafamidis, acoramidis) that must be taken daily or gene silencers (patisiran, vutrisiran) that require ongoing doses, a single infusion of nexiguran ziclumeran could potentially provide lifelong TTR reduction. If it works as intended, it would be a one-time treatment rather than ongoing therapy.

CRISPR-Cas9 is a technology that allows scientists to make precise changes to DNA inside living cells. It works like molecular scissors that cut the DNA at a specific location, guided by a short RNA sequence. In nexiguran ziclumeran, CRISPR is used to cut and disable the TTR gene in liver cells, permanently stopping those cells from producing the transthyretin protein that causes amyloidosis. The edit is permanent because it changes the actual DNA code.

The FDA placed the MAGNITUDE Phase 3 trials on clinical hold on October 29, 2025, after a patient had grade 4 liver enzyme rises and raised bilirubin following treatment; that patient died on November 5, 2025, in what Intellia called a case with complicating comorbidities. Because nexiguran ziclumeran uses lipid nanoparticles to deliver its editing components to liver cells, liver safety is watched closely. The FDA lifted the hold on MAGNITUDE-2 (the nerve form of the disease) on January 27, 2026, and on MAGNITUDE (the heart form) on March 2, 2026. Intellia added liver-test monitoring to the trials.

In the Phase 1 study of 36 people with the nerve form of hereditary ATTR, a single infusion lowered TTR protein by 90% at day 28, and it was still 92% lower at 24 months without more dosing^[5]. However, Phase 1 trials involved small numbers of patients, and the safety signal that emerged in Phase 3 underscores the importance of larger trials.

No. Nexiguran ziclumeran is not FDA-approved and is available only in clinical trials. The FDA lifted the 2025 clinical hold on both Phase 3 trials in early 2026. Patients with ATTR amyloidosis should discuss currently approved treatment options with their physician.

Off-target editing, where CRISPR cuts DNA at unintended locations, is a theoretical concern with any gene editing therapy. Intellia has designed nexiguran ziclumeran to minimize off-target activity, and preclinical studies showed high specificity for the TTR gene. The cause of the liver events that paused the trials has not been fully explained. In August 2026 Intellia reported that the highest liver enzyme rises occurred in patients carrying one specific HLA allele, an immune-system gene type. Long-term follow-up of treated patients will be essential to fully understand the safety profile of in vivo gene editing.