Intellia's gene therapy shows promise for rare heart condition

Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) manifests primarily through symptoms linked to heart failure and reduced cardiac function. Intellia Therapeutics has recently unveiled promising early-stage clinical data indicating that its investigational gene editing therapy might stabilize or improve the prognosis for patients suffering from this rare and progressively debilitating heart condition.

The data comes from a Phase I trial (NCT04601051) that involved 36 patients, revealing that a single dose of NTLA-2001 (nexiguran ziclumeran) led to a median enhancement of five meters in the six-minute walk test—a standard evaluation tool for lung and heart capacity. Furthermore, 92% of participants showed either improvement or maintenance in their New York Heart Association (NYHA) class, a critical measure for determining the severity of heart failure.

These findings were presented by the US-based company at the 2024 American Heart Association scientific meeting held on November 16 in Chicago. John Leonard, CEO of Intellia, highlighted that these preliminary results offer compelling evidence that NTLA-2001 has the potential to alter the progression of ATTR amyloidosis. Leonard remarked on the significance of the stability or improvement observed in various markers of cardiac disease progression following just a single dose of NTLA-2001, particularly given the high percentage of patients with advanced cardiomyopathy.

ATTR amyloidosis is characterized by the accumulation of misfolded transthyretin (TTR) proteins in the heart, leading to impaired cardiac function. NTLA-2001 utilizes clustered regularly interspaced short palindromic repeat (CRISPR) technology to deactivate the TTR gene, thereby reducing the production of the problematic protein. The Phase I trial demonstrated an average TTR reduction of 90% after one year.

Following these encouraging results, Intellia is now advancing NTLA-2001 into the pivotal Phase III MAGNITUDE trial (NCT06128629), which will involve 765 patients and compare the investigational CRISPR therapy to a placebo in ATTR-CM. The first patient was administered the treatment in this randomized, double-blind trial in March 2024.

NTLA-2001 is being developed in collaboration with Regeneron. The partnership between Intellia and the US biotech firm began in 2016 and was further expanded in October 2023, extending Intellia’s financial runway through to 2026.

In 2019, Pfizer received US Food and Drug Administration (FDA) approval for Vyndamax (tafamidis) and Vyndaqel (tafamidis meglumine), which are currently the only approved therapies for ATTR-CM. Pfizer reported $3.3 billion in sales for these drugs in 2023, though projections indicate a decline to $1.9 billion by 2030 due to the expiration of patents in 2026, according to GlobalData.

Market analysts from GlobalData forecast that NTLA-2001 could generate up to $1.2 billion in revenue for Intellia by 2030. This announcement arrives amidst increasing competition in the ATTR-CM treatment landscape, with two new drugs—BridgeBio’s acoramidis and Alnylam’s vutrisiran—preparing for approval following successful Phase III outcomes.