Intellia's MAGNITUDE-2 Freed From Regulatory Hold, Resumes Patient Enrollment

Intellia Therapeutics has received significant news from the FDA: the regulatory agency has removed the clinical hold on its MAGNITUDE-2 Phase 3 trial. This decision allows the biotech company to restart patient enrollment and dosing for nexiguran ziclumeran (nex-z), a gene-editing therapy designed to treat hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). The move marks a critical turning point for the company’s CRISPR-based treatment program after months of regulatory scrutiny.

Breaking Through The Clinical Hold

The MAGNITUDE and MAGNITUDE-2 trials were placed under regulatory hold in October 2025 following a safety concern in the MAGNITUDE study. A patient experienced Grade 4 elevations in liver transaminases and increased total bilirubin levels, triggering the FDA’s protocol-defined pause. Rather than viewing this as a dead-end, Intellia treated the event as an opportunity to strengthen its safety framework. The company worked collaboratively with FDA investigators to develop comprehensive risk-mitigation strategies, demonstrating the kind of adaptive approach regulators increasingly expect from developers of cutting-edge therapies.

The FDA’s decision to lift the hold for MAGNITUDE-2 signals confidence in Intellia’s revised development strategy. The company has aligned with regulators on enhanced monitoring protocols, particularly more rigorous liver laboratory testing. This enhanced surveillance is now embedded in the updated trial protocol, setting a new safety standard for similar gene-editing programs.

Enhanced Safety Monitoring Unlocks Trial Progression

Under the amended protocol, MAGNITUDE-2 will proceed as a randomized, double-blind, placebo-controlled Phase 3 study. The trial will evaluate a single 55 mg infusion of nex-z in patients with ATTRv-PN. Notably, the target enrollment has been expanded from approximately 50 to 60 patients. The study’s primary goals include assessing changes in modified neuropathy impairment score and serum transthyretin (TTR) levels—key indicators of the drug’s efficacy.

Intellia is now mobilizing its global network of investigators and ethics committees to restart enrollment as quickly as possible. Separately, engagement with the FDA continues regarding the MAGNITUDE Phase 3 trial for transthyretin amyloidosis with cardiomyopathy (ATTR-CM), which remains on hold pending further regulatory alignment.

Next-Generation Gene-Editing Therapy Shows Promise Despite Setbacks

Nex-z represents a novel approach to treating rare genetic diseases. Based on CRISPR/Cas 9 gene-editing technology, the drug is engineered to permanently inactivate the TTR gene—offering the potential to become the first one-time curative treatment for ATTRv-PN and ATTR-CM. This contrasts sharply with conventional therapies that merely manage symptoms. Interim Phase 1 data have already demonstrated deep and sustained reductions in serum TTR levels following a single dose, validating the therapeutic concept.

The regulatory pathway has also been accelerated through FDA’s RMAT (Regenerative Medicine Advanced Therapy) designation and Orphan Drug status, recognizing both the innovation and the unmet medical need in treating this rare condition. The European Commission has similarly granted Orphan Drug Designation, positioning nex-z for potential global impact.

Intellia’s stock (NTLA) reflects the market’s assessment of the program’s progress. Over the past year, the stock has traded within a range of $5.90 to $28.25. Recent trading activity shows investor optimism following the hold removal, with the stock trading higher in early sessions. The ability to resume enrollment represents tangible validation of the company’s scientific approach and regulatory engagement strategy, reinforcing confidence that the hold has been overcome through methodical safety improvements rather than blind chance.