• acoramidis
• ag10
• amyloid cardiomiopathy
• amyloidosis
• ATTR
• ATTR-CM
• ATTRm
• ATTRwt
• heart
• transthyretin
• TTR
• TTR stabilizers

Acoramidis, also known as AG10, represents a novel therapeutic approach for transthyretin amyloid cardiomyopathy (ATTR-CM). ATTR-CM is a progressive and life-threatening disease characterized by the deposition of mutant or wild-type transthyretin (TTR) amyloid fibrils in the myocardium, leading to heart failure and other severe cardiac complications. Wild-type TTR is responsible for ATTRwt-CM in older individuals, while mutant TTR causes familial or mutant ATTR amyloidosis (ATTRm). Previously, treatments for ATTR-CM were limited to managing symptoms. However, improvements in the management of ATTR amyloidosis have led to the development of disease-modifying treatments which can be classified according to their mechanism, such as stabilizers, knockdown (including silencers), and depletion-inducing agents.
Acoramidis is a potent and selective stabilizer of TTR engineered to replicate the effects of the specific TTR variant T119M, known for hyper-stabilizing tetramers formed with either wild-type or mutant TTR. Preclinical studies showed acoramidis to be more potent, with better binding affinity and site occupancy in both wild-type and mutant TTR, compared to other TTR stabilizers like tafamidis, diflunisal, and tolcapone, leading to the execution of phases 1, 2, and 3 clinical trials. Acoramidis successfully passed these trials, resulting in the FDA approval of the New Drug Application and the EMA acceptance of the Marketing Authorization Application