Intellia Therapeutics has announced promising early-stage clinical data for its investigational gene editing treatment, NTLA-2001 (nexiguran ziclumeran), suggesting it may stabilize or improve outcomes for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). This rare and progressive heart condition occurs when misfolded transthyretin (TTR) proteins accumulate in the heart, impairing its function. The results were presented at the 2024 American Heart Association scientific meeting.
Phase I Study Results
The Phase I study (NCT04601051) involved 36 patients. One year after a single dose of NTLA-2001, patients experienced a median five-meter improvement in the six-minute walk test, a common measure of lung and heart function. Furthermore, 92% of patients either improved or maintained their New York Heart Association (NYHA) class, a key metric for assessing heart failure severity.
Intellia’s CEO John Leonard stated that these early results provide evidence that NTLA-2001 has the potential to modify the progression of ATTR amyloidosis. "The stability or improvement observed after a single dose of NTLA-2001 in multiple markers of cardiac disease progression is remarkable, especially considering the high proportion of patients with cardiomyopathy who had advanced heart failure," Leonard said. He also noted similar positive trends in patients with hereditary ATTR amyloidosis with polyneuropathy.
Mechanism of Action and TTR Reduction
NTLA-2001 employs clustered regularly interspaced short palindromic repeat (CRISPR) technology to inactivate the TTR gene, reducing the production of the problematic protein. The Phase I study demonstrated a mean TTR reduction of 90% after one year.
Ongoing Phase III Trial
Intellia is currently evaluating NTLA-2001 in the pivotal 765-patient Phase III MAGNITUDE trial (NCT06128629), comparing the CRISPR therapy to a placebo in ATTR-CM patients. The first patient was dosed in this randomized, double-blind trial in March 2024.
Collaboration and Market Context
NTLA-2001 is being developed in collaboration with Regeneron. The companies initially teamed up in 2016 and expanded their research collaboration in October 2023.
Currently, Pfizer's Vyndamax (tafamidis) and Vyndaqel (tafamidis meglumine) are the only FDA-approved therapies for ATTR-CM, generating $3.3 billion in sales in 2023. However, GlobalData market analysts predict that NTLA-2001 could generate up to $1.2 billion in revenue for Intellia by 2030, despite anticipated competition from other emerging therapies like BridgeBio’s acoramidis and Alnylam’s vutrisiran.
