ATTR Amyloidosis MAGNITUDE Clinical Trials Temporarily on Hold

There has been an important update regarding the MAGNITUDE (NCT06128629) and MAGNITUDE-2 (NCT06672237) clinical trials evaluating nexiguran ziclumeran (nex-z, also known as NTLA-2001) for transthyretin (ATTR) amyloidosis.

Nex-z is an experimental (not yet approved) gene-editing treatment being developed for people with ATTR amyloidosis. It uses a technology called CRISPR/Cas9, which is designed to knockdown or “turn off” the gene in the liver that makes transthyretin (TTR), the protein that becomes unstable and forms amyloid deposits in the body. By reducing how much TTR the body produces, the goal is to slow or stop the progression of amyloidosis.

On October 27, 2025, Intellia Therapeutics temporarily paused enrollment in its MAGNITUDE and MAGNITUDE-2 trials after one participant experienced Grade 4 elevations in liver transaminases (i.e., very high liver enzyme levels) and an elevated bilirubin, meeting the study’s pre-defined safety criteria. The participant was hospitalized and is receiving appropriate care. Two days later, on October 29, the U.S. Food and Drug Administration verbally placed both trials on clinical hold and indicated that a formal letter outlining next steps will follow within 30 days.

Why is this one case requiring a clinical hold?

More than 450 participants have received nex-z as part of the MAGNITUDE clinical trials. While this safety event represents a single case among hundreds of treated patients, the study protocol includes pre-defined rules requiring a pause whenever certain safety thresholds are met. These built-in safeguards are designed to protect trial participants and allow time for careful review. The temporary pause enables Intellia and regulatory authorities to thoroughly assess what caused the event, determine whether it could occur again, and identify any steps needed to ensure continued safety before enrollment resumes.

What this means for current MAGNITUDE study participants or patients seeking to enroll in either study:

• Enrollment of new participants is temporarily paused.
• Participants already enrolled will continue to be closely monitored by their study teams in coordination with Intellia and regulatory authorities.
• The company is working with independent experts to better understand the cause of the liver enzyme elevations and to determine appropriate safety measures moving forward.

What happens next?

Intellia is collaborating with the FDA and global health authorities to assess the data and identify potential risk-mitigation strategies. The company has stated its commitment to participant safety and to resuming enrollment as soon as it is appropriate to do so.

ARC will continue to monitor developments closely and share updates with the community as new information becomes available.

If you are participating in a MAGNITUDE study or were considering enrollment, we encourage you to contact your study investigator or clinical site for any questions about your specific situation.

You can also contact Intellia at medicalinformation@intelliatx.com or 1-857-285-6200 ext 6 for more information regarding the study.