Intellia Therapeutics has announced early-stage clinical data suggesting that its investigational gene editing treatment may stabilise or improve outcomes for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM), a rare and progressive heart condition.
The Phase I study (NCT04601051), involving 36 patients, showed that one year after a single dose of NTLA-2001 (nexiguran ziclumeran), patients experienced a median five-meter improvement in the six-minute walk test – a common measure of lung and heart function.
Additionally, 92% of patients either improved or maintained their New York Heart Association (NYHA) class, a key metric for assessing heart failure severity.
The US-based company presented the data at the 2024 American Heart Association scientific meeting on Saturday 16 November in Chicago. Intellia’s CEO John Leonard said in a statement 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.
“We observed similarly positive and consistent trends, indicative of a disease-modifying effect, in patients with hereditary ATTR amyloidosis with polyneuropathy.”
ATTR amyloidosis occurs when misfolded transthyretin (TTR) proteins accumulate in the heart, impairing its function. 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 showed a mean TTR reduction of 90% after one year.
Intellia is now evaluating NTLA-2001 in the pivotal 765-patient Phase III MAGNITUDE trial (NCT06128629), which is comparing the investigational CRISPR therapy to a placebo in ATTR-CM. The first patient was dosed in the randomised, double-blind trial in March 2024.
NTLA-2001 is being developed in collaboration with Regeneron. Intellia and the US biotech initially teamed up in 2016, but the companies entered an expanded research collaboration in October 2023. This move helped extend Intellia’s cash runway through to 2026.
In 2019, Pfizer secured US Food and Drug Administration (FDA) approval for Vyndamax (tafamidis) and Vyndaqel (tafamidis meglumine) – the only currently approved therapies for ATTR-CM. The drugs pulled in $3.3bn in sales in 2023, as per Pfizer’s financials. However, sales are expected to drop to $1.9bn by 2030 due to patent expiry in 2026, as per GlobalData, the parent company of Pharmaceutical Technology.
GlobalData market analysts predict that NTLA-2001 could generate up to $1.2bn in revenue for Intellia by 2030.
The announcement comes as competition in the ATTR CM treatment space intensifies. Two new drugs – BridgeBio’s acoramidis and Alnylam’s vutrisiran – are gearing up for approval after successful Phase III readouts.
