Intellia Therapeutics has paused enrolment in two clinical trials of its transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN) gene therapy after a patient was hospitalised.
In the Phase III MAGNITUDE trial (NCT06128629) of nex-z, also known as nexiguran ziclumeran, a patient suffered Grade 4 liver transaminases and increased total bilirubin after being dosed on 30 September 2025. The patient was hospitalised and is receiving medical intervention while being closely monitored, according to Intellia.
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As a result, the company is consulting with experts, considering potential risk mitigation strategies and engaging with regulatory authorities.
Intellia President and CEO Dr John Leonard said: “In line with our commitment to patient safety, we have taken immediate action to temporarily pause enrolment in MAGNITUDE and MAGNITUDE-2 as we investigate this recent event. As we focus on ensuring the health of this patient, we are also engaging with regulatory authorities and other stakeholders globally to develop a strategy to resume enrolment as soon as appropriate.”
While the adverse event (AE) has occurred in the MAGNITUDE trial, as a precaution, Intellia has also paused dosing in MAGNITUDE-2 (NCT06672237). The two trials have collectively recruited 697 patients, with more than 450 having been dosed with Nex-z.
Intellia’s stock took a hit in the wake of the announcement, dropping by 47.8% from $25.31 at market close on 24 October to $13.21 at market close on 27 October.
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By GlobalDataIntellia has been in this situation before. In May 2025, a patient suffered an asymptomatic grade 4 liver transaminase elevation. At the time, Intellia said it appeared as if the patient was recovering without the need for hospital treatment.
Being developed in partnership with Regeneron, Nex-z is an in vivo CRISPR based gene therapy, gained Regenerative Medicine Advanced Therapy (RMAT) designation from the US Food and Drug Administration (FDA) in December 2024.
Intellia not alone in gene therapy AEs
Intellia is not alone in suffering safety concerns with gene therapies. Sarepta Therapeutics’ gene therapy Elevidys (delandistrogene moxeparvovec) for Duchenne muscular dystrophy (DMD) has suffered clinical holds and a new black box warning following 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.
Elevidys and SRP-9004 both use the same recombinant adeno-associated viral vector (AAV) in AAVrh74.
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).
Oncology is predicted to continue as the top therapy area, followed by central nervous system (CNS) disorders and metabolic disorders.
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