Intellia Therapeutics has been given approval to resume patient enrolment and dosing in a Phase III trial of its gene therapy for a rare genetic disease.
The US Food and Drug Administration (FDA) put a clinical hold on two Phase III trials, MAGNITUDE (NCT06128629) and MAGNITUDE-2 (NCT06672237), on 29 October 2025 after a patient in Intellia’s former trial developed Grade 4 liver transaminases and increased total bilirubin after being dosed with nexiguran ziclumeran (nex-z). The patient has since died.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
The trials are investigating the efficacy and safety of nex-z in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN).
The agency has now removed the hold on MAGNITUDE-2, a randomised, double-blind, placebo-controlled trial, after Intellia aligned with the FDA on certain study modifications and mitigation measures, including enhanced safety monitoring of liver laboratory tests.
The agreement also dictates that Intellia increase the trial’s target enrolment from approximately 50 patients to approximately 60 patients with ATTRv-PN. The primary endpoints of the study are a change in the modified neuropathy impairment score and a change in serum TTR levels.
CEO and President of Intellia, Dr John Leonard, said: “We appreciate the FDA’s expeditious review of our submission and ongoing engagement and thank our study investigators and patients for their continued participation. With the clinical hold for MAGNITUDE-2 lifted, our team is focused on resuming patient enrolment as quickly as possible as we seek to advance this potential one-time treatment option for people living with ATTRv-PN.”
US Tariffs are shifting - will you react or anticipate?
Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis.
By GlobalDataAfter the hold was released, Intellia’s stock rose 18.35%, from $13.95 at market close on 26 January to $16.51 at market open on 27 January. While still up on the previous day, the stock value did flatten slightly during the day, closing at $14.83.
The clinical hold remains in place for the MAGNITUDE study.
Speaking at the JP Morgan Healthcare Conference in January 2026, Leonard said that the patient’s death was due to sepsis after a perforation and ulcer were found in the patient’s abdomen during surgery, with the company believing that the death was therefore not related to liver failure.
Being developed in partnership with Regeneron, nex-z is an in vivo clustered regularly interspaced short palindromic repeats (CRISPR)-based gene therapy that gained Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA in December 2024.
This is not the first case of a death in a gene therapy trial. Cases have also been reported by both Sarepta Therapeutics and Pfizer, which each had deaths in their Duchenne muscular dystrophy (DMD) gene therapy trials, causing Pfizer to conclude development of its candidate.
Cell & Gene therapy coverage on Clinical Trials Arena is supported by Cytiva.
Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content.
