FDA lifts final clinical hold on Intellia’s MAGNITUDE Phase 3 trial for CRISPR therapy nex-z in ATTR-CM, fully clearing nex-z program after January MAGNITUDE-2 resolution. Enrollment resumes
Written By: Nikita Chaudhari BPharm
Reviewed By: Pharmacally Editorial Team
Intellia Therapeutics, Inc. a pioneer in CRISPR/Cas9 gene editing, announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on the Investigational New Drug (IND) application for the MAGNITUDE Phase 3 trial. This pivotal decision clears the path for Nexiguran Ziclumeran (nex-z), a one-time infusion therapy targeting transthyretin amyloidosis with cardiomyopathy (ATTR-CM), a progressive condition where misfolded transthyretin (TTR) protein deposits damage the heart.
This follows the FDA’s January 2026 resolution of the hold on MAGNITUDE-2 (ATTRv-PN), completing clearance across Intellia’s nex-z Phase 3 program. Both holds were initiated October 29, 2025, after a MAGNITUDE patient experienced Grade 4 liver transaminase elevations and bilirubin increase post-dosing.
This event triggered protocol-defined pausing criteria. Intellia collaborated closely with the FDA to implement enhanced safety protocols, including stricter liver function monitoring, short-term steroid use for early transaminase spikes, and exclusions for patients with pre-existing liver issues. For MAGNITUDE specifically, new criteria now bar those with recent cardiovascular instability or ejection fraction below 25% at screening.
“We are very pleased to have aligned with the FDA on the path forward,” said Intellia President and CEO John Leonard, M.D. This resolution follows a similar lift in January for the MAGNITUDE-2 Phase 3 trial in hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). With both trials now advancing, Intellia aims to complete enrollment soon, engaging investigators, ethics committees, and global regulators.
Trial Details and Design
MAGNITUDE (NCT06128629) enrolls about 1,200 ATTR-CM patients in a 2:1 randomized, double-blind, placebo-controlled setup. Participants receive a single 55 mg nex-z infusion or placebo, with the primary endpoint tracking a composite of cardiovascular events like mortality.
MAGNITUDE-2 (NCT06672237) targets roughly 60 ATTRv-PN patients in a 1:1 design, measuring changes in modified neuropathy impairment scores and serum TTR levels.
These trials build on Phase 1 data showing nex-z’s deep, durable TTR reduction key to halting amyloid buildup. Nex-z, co-developed with Regeneron Pharmaceuticals, holds FDA Orphan Drug and RMAT designations, plus European Orphan Drug status, underscoring its potential as a transformative, one-time treatment.
Broader Implications for CRISPR in ATTR Amyloidosis
ATTR-CM and ATTRv-PN affect thousands worldwide, with limited options beyond symptom management or liver transplants. Nex-z’s gene-editing approach inactivates the TTR gene at its source, offering hope for broad patient populations. Resuming these Phase 3 trials marks a critical milestone for Intellia, potentially accelerating approval amid growing CRISPR momentum in rare diseases. Intellia now focuses on rapid enrollment while prioritizing safety.
Reference
Intellia Therapeutics Announces FDA Lift of Clinical Hold on MAGNITUDE Phase 3 Clinical Trial in ATTR-CM, 02 March 2026, Intellia Therapeutics Announces FDA Lift of Clinical Hold on MAGNITUDE Phase 3 Clinical Trial in ATTR-CM – Intellia Therapeutics
Intellia Pauses Phase 3 CRISPR Trials after Life-Threatening Liver Injury in Transthyretin Amyloidosis (ATTR) Patient, 29 October 2026, https://pharmacally.com/intellia-pauses-phase-3-crispr-trials-after-life-threatening-liver-injury-in-transthyretin-amyloidosis-attr-patient/
FDA Lifts Clinical Hold on Intellia’s MAGNITUDE-2 Phase 3 Trial of Nex-z in ATTRv-PN, 27 January 2026, https://pharmacally.com/fda-lifts-clinical-hold-on-intellias-magnitude-2-phase-3-trial-of-nex-z-in-attrv-pn/
About Writer
Nikita Santosh Chaudhari, BPharm
She is a pharmacy graduate with a keen interest in clinical research, pharmacovigilance, and medical writing, particularly inclined towards publication writing and scientific content development. In her words, she is enthusiastic about scientific documentation and publication writing, aiming to contribute to accurate, ethical, and evidence-based medical communication.