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The FDA has approved BridgeBio’s acoramidis (Attruby), a transthyretin (TTR) stabilizer, for cardiac amyloidosis (ATTR-CM). It is the second drug to be approved for this heart disease,

chasing Pfizer’s TTR stabilizer tafamidis (Vyndaqel/Vyndamax). Several other biopharma companies expect to soon have drugs on the market for this form of amyloidosis. “The need for more

treatment options for patients living with ATTR-CM is crucial to achieving the goal of better outcomes and improved quality of life,” said Muriel Finkel, President of Amyloidosis Support

Groups, a non-profit organization to support amyloidosis patients. ATTR-CM is a cardiac amyloidosis, caused by misfolding of the transport protein TTR. TTR is produced in the liver, but its

amyloid fibrils can clog up the heart — causing symptoms that are similar to heart failure. ATTR-CM was once considered a rare disease, but drug developers now estimate that 300,000–500,000

people worldwide are affected. It can be hard to diagnose, however. Pfizer secured a first FDA approval for a TTR stabilizer, the small molecule tafamidis, in 2019. Acoramidis was discovered

by researchers at Stanford, and showed improved stabilization of the pathogenic protein in in vivo assays. BridgeBio estimates that acoramidis stabilizes more than 90% of the TTR protein.

The FDA approved the drug on the basis of the phase III ATTRibute-CM study in 632 ATTR-CM patients. The trial met its primary endpoint, a composite analysis of all-cause mortality,

cardiovascular-related hospitalization, change in N-terminal prohormone of brain natriuretic peptide levels, and the six-minute walk distance. The drug provided a ‘win ratio’ of 1.8, show

data in in _The New England Journal of Medicine_, with 64% of pairwise comparisons favouring acoramidis and 36% favouring placebo. The trial met several key secondary endpoints, showing for

example a mean difference of 39.6 m in favour of acoramidis in the six-minute walk distance at 30 months. The trial did not show a benefit in the all-cause mortality at 30 months, but a

longer-term open-label extension analysis found this benefit by 36 months. Common side effects included diarrhoea and abdominal pain. Tafamidis and acoramidis have not been compared in

head-to-head trials. Pfizer earned US$3.3 billion for tafamidis in 2023. Analysts forecast blockbuster potential for acoramidis too. BridgeBio expects the global annual ATTR market to reach

$15–20 billion. Other firms are chasing this opportunity. Partners Ionis and AstraZeneca are seeking supplementary approval for their antisense drug eplontersen _(_Wainua) in ATTR-CM, as is

Alnylam for its RNAi-based drug vutrisiran (Amvuttra). Both act by knocking down TTR expression in the liver, and both are already approved for polyneuropathy of hereditary ATTR amyloidosis.

Regeneron and Intellia are meanwhile co-developing ziclumeran, a CRISPR–Cas9-based editor that deletes TTR from hepatocytes. A phase III trial of this gene editor in ATTR-CM started in

November.