NTLA-2001, an experimental hereditary transthyretin amyloidosis (hATTR) therapy, led to rapid and deep reductions in serum transthyretin (TTR) in a phase 1 clinical trial, as announced in a press release.

The trial tested the therapy’s safety, tolerability, pharmacokinetics, and pharmacodynamics. Moreover, the clustered regularly interspaced short palindromic repeats (CRISPR)-based therapy was generally well tolerated. 

“We’re encouraged to see profound and sustained serum TTR reductions in people with cardiomyopathy manifestations of this rare and fatal disease, further bolstering the prospects for a one-time, in vivo treatment for multiple ATTR patient groups,” said George D. Yancopoulos, MD, PhD, the president and chief scientific officer of Regeneron, the codevelopers of the treatment together with Intellia.

“These new interim results demonstrate that NTLA-2001 can profoundly reduce serum TTR levels in patients whose condition results in cardiomyopathy,” added John Leonard, MD, the president and chief executive officer of Intellia.

Read more about NTLA-2001 and other experimental therapies for hATTR 

The results follow the cardiomyopathy arm of the study and show a 93% or 92% reduction in TTR levels after a single dose of 0.7 or 1 mg/kg of intravenous NTLA-2001, respectively. Twelve patients with ATTR, cardiomyopathy, and heart failure were treated and followed for 2 to 6 months. The reduction in the misfolded TTR protein was sustained throughout the follow-up period. 

“These data support NTLA-2001’s potential as a one-time treatment to permanently inactivate the TTR gene and reduce the disease-causing protein,” the press release reported.

The companies will now test the lower-dose treatment in the ongoing dose-expansion portion of the study. Following the completion of the phase 1 trial, which is taking place in New Zealand, Sweden, and the UK, the companies are planning to initiate a pivotal clinical trial that will also include patients in the United States.

hATTR is a rare progressive disease characterized by the accumulation of misfolded TTR proteins that cause damage to multiple organs and organ systems. NTLA-2001 targets the mutated TTR gene that produces the faulty TTR protein, thereby reducing its levels in the body.


Intellia and Regeneron announce initial data from the cardiomyopathy arm of ongoing phase 1 study of NTLA-2001, an investigational CRISPR therapy for the treatment of transthyretin (ATTR) amyloidosis. News release. Intellia Therapeutics; September 16, 2022.

Study to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of NTLA-2001 in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and patients with transthyretin amyloidosis-related cardiomyopathy (ATTR-CM). ClinicalTrials.gov. Updated December 29, 2021. Accessed October 4, 2022.