Acoramidis may be new player in ATTR-CM

Acoramidis has emerged as an important player in the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), demonstrating encouraging results in the phase III ATTRibute-CM trial.

ATTR-CM results from aggregation and deposition of transthyretin amyloid fibrils in the myocardium and heart tissues. Acoramidis stabilizes the TTR tetramer and prevents the production of fibrils.

In ATTRibute-CM, acoramidis 800 mg twice daily significantly reduced the primary endpoint, a hierarchical analysis of all-cause mortality, cardiovascular hospitalizations, and change from baseline in N-terminal pro–B-type natriuretic peptide (NT-proBNP), and 6-minute walking distance compared with placebo (win ratio 1.77).

“Remarkably, the overall survival and cardiovascular hospitalization rates approached that of age-matched populations without ATTR-CM,” said lead investigator Dr Julian Gillmore from the University College London/Royal Free Hospital, UK, during a press conference at ESC 2023.

“ATTRibute-CM was a robustly positive trial, showing benefits across the board for acoramidis and the tantalizing possibility of genuine clinical improvements,” Gillmore added.

Once approved by the US FDA, acoramidis would be the second drug targeted to treat ATTR-CM, the first being tafamidis.

Positive outcomes

The study included 632 patients (mean age 77 years, 90 percent male) with a diagnosis of ATTR-CM and NYHA class I-III symptoms.

Acoramidis led to a relative 50-percent reduction in the risk for cardiovascular hospitalization, which is one component of the primary endpoint. Key secondary endpoints also showed a consistent benefit with acoramidis across multiple measures of disease activity, including NT-proBNP levels, exercise tolerance, quality of life, and serum transthyretin levels, reported Gillmore.  

When asked how acoramidis fared with tafamidis, the first drug approved for ATTR-CM, discussant Dr Thibaud Damy from the University Hospital Henri Mondor, Creteil, France, said there are differences in the ATTRibute-CM trial and the ATTR-ACT trial of tafamidis.

While patients in ATTRibute-CM were older than those in ATTR-ACT, they were not as sick, he explained. To elucidate, he said a larger percentage of patients in ATTRibute-CM had NYHA class I/II heart failure, and baseline NT-proBNP levels were higher. “This is reflected in the all-cause mortality rates of the placebo-treated patients in ATTRibute-CM and ATTR-ACT which were 29.5 percent and 42.9 percent, respectively.”

Another difference between the two trials was the background treatment. Patients could be treated with tafamidis at 12 months based on physician discretion. In the end, 14.5 percent of those treated with acoramidis and 21 percent of those on placebo received tafamidis.

Potential impact of tafamidis

Gillmore, meanwhile, said the addition of tafamidis could have diluted the effect of acoramidis. Despite the use of tafamidis in ATTRibute-CM, he does not envision the use of both agents together.  

ESC Hot Line session moderator, Dr Faiez Zannad from the University of Lorraine, Nancy, France, commented that a head-to-head trial of tafamidis and acoramidis is unlikely, but physicians will want to know how the drugs play off against each other.

The manufacturers of acoramidis is expected to file a regulatory approval in the US this year. As for tafamidis, it is US FDA-approved for the treatment of cardiomyopathy of wild type or hereditary ATTR-CM.

As therapy for ATTR-CM may be most effective when administered before significant cardiac dysfunction, experts said early identification of affected individuals is essential.