A patient dosed with Intellia Therapeutics’ CRISPR gene therapy has died after suffering a severe liver-associated adverse event (AE).
The patient had been dosed with nex-z (nexiguran ziclumeran) in the Phase III MAGNITUDE trial (NCT06128629) on 30 September 2025. After this, the patient suffered Grade 4 liver transaminases and increased total bilirubin and was hospitalised.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
Two Phase III trials of the candidate were paused by Intellia on 27 October, before being put on an official hold by the US Food and Drug Administration (FDA) two days later (29 October).
In a 6 November announcement, Intellia President and CEO Dr John Leonard said: “We were deeply saddened to learn that the patient who experienced Grade 4 liver transaminase elevations and increased total bilirubin following a dose of nex-z in the MAGNITUDE Phase III clinical trial, as reported on 27 October, passed away last night.
“We have been advised by the treating physician that this is a case with complicating comorbidities, and it is being further evaluated. 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.”
Intellia’s stock dropped by 8.74% to a price of $12.32 on 6 November market close, down from a $13.50 close on 5 November; however, premarket analysis suggests a more significant drop at market open on 7 November.
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 GlobalDataThis came after a significant drop of 47.8% from $25.31 at market close on 24 October to $13.21 at market close on 27 October, when the AE was first reported.
Being developed in partnership with Regeneron, nex-z is an investigational in vivo CRISPR-based therapy designed to inactivate the TTR gene in the liver to prevent the production of transthyretin (TTR) protein. It gained regenerative medicine advanced therapy (RMAT) designation from the FDA in December 2024.
There are nearly 700 patients enrolled between both studies, with Grade 4 liver transaminase elevations having been reported in less than 1% of all patients enrolled in MAGNITUDE and no Grade 4 liver transaminase elevations have been reported in MAGNITUDE-2.
Another Grade 4 liver-associated AE was announced in May 2025, however, the patient was asymptomatic and recovered without hospital intervention.
Gene therapy has previously led to deaths
This is not the first gene therapy-associated death, with both Sarepta Therapeutics and Pfizer suffering fatalities in their gene therapy trials recently
Sarepta Therapeutics’ gene therapy Elevidys (delandistrogene moxeparvovec) for Duchenne muscular dystrophy (DMD) has been associated with two patient deaths due to acute liver failure, one in March 2025 and one in June 2025.
Sarepta also suffered a patient death in a Phase I trial of SRP-9004 in limb-girdle muscular dystrophy Type 2E/R4 (LGMD2E/R4) also reported a patient death.
Pfizer also reported fatality in the Phase II DAYLIGHT trial (NCT05429372) evaluating its DMD gene therapy fordadistrogene movaparvovec, with a three-year-old boy having suffered a cardiac arrest. Pfizer has now discontinued development of the gene therapy after it also failed to show benefit in a Phase III trial.
According to GlobalData’s report, ‘The State of the Biopharmaceutical Industry 2025 – Mid-Year Update’, the global cell and gene therapy (CGT) market is estimated to be worth $79.3bn by 2030, with a 40% compound annual growth rate (CAGR).
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.
