Cardiac amyloidosis: Acoramidis reduces mortality and improves quality of life
The non-hereditary form of transthyretin amyloidosis, known as wild-type, primarily affects men over 65. Heart failure and arrhythmias, as well as decreased physical endurance, are typical symptoms. / © Adobe Stock/InsideCreativeHouse
Amyloidosis develops from deposits of misfolded proteins. Various proteins can trigger amyloidosis, and the amyloid fibrils can accumulate in many organs. Transthyretin (ATTR) amyloidosis and light chain (AL) amyloidosis are particularly important for the heart .
The protein transthyretin is produced primarily in the liver and is responsible for the transport of vitamin A and thyroid hormones. Four monomers together form a transport body.
In people with ATTR amyloidosis, this tetramer is defective and breaks down. This can be caused by either an inherited genetic defect or advancing age. Misfolding causes the protein monomers to aggregate into oligomeric amyloid precursors, which accumulate in the heart, where they organize into amyloid fibrils.
Acoramidis, like the already available tafamidis (Vyndaquel®) , is a specific TTR stabilizer. It forms hydrogen bonds between neighboring serine residues within both thyroxine binding sites of the tetramer. This interaction increases the stability of the tetramer, inhibits its dissociation into monomers, and thus slows the amyloidogenic process that leads to ATTR cardiomyopathy. Nearly complete transthyretin stabilization was observed with acoramidis in wild-type (box) and in all tested amyloidogenic genotype variants.
The film-coated tablets, each containing 356 mg of acoramidis (Beyonttra®, Bayer), are approved for the treatment of wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM). Patients take two tablets, equivalent to 712 mg of acoramidis, twice daily with water and without regard to meals. The total daily dose is 1424 mg. If the patient misses a dose, they should take the next dose at the next regularly scheduled time.
Limited data are available for patients with severe renal impairment (creatinine clearance below 30 ml/min), and none for dialysis patients. Since the drug has not been tested in patients with liver failure, it is not recommended in these patients.
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