Acoramidis, a transthyretin stabilizer used to treat transthyretin-mediated cardiomyopathy (ATTR-CM), was developed in the early 2020s and approved for medical use in 2024. Its history is marked by its effectiveness in slowing the progression of heart disease caused by misfolded transthyretin proteins, with clinical trials demonstrating reduced cardiovascular-related hospitalizations and death. Acoramidis, an oral therapy taken as tablets, was approved in the United States in 2024 and is included in treatment regimens for adults with ATTR-CM. Its development featured targeted molecular design and pivotal clinical studies that allowed early patient access under monitored programs.
BRAND NAMES
Attruby : This is the marketed name under which acoramidis is prescribed for transthyretin-mediated cardiomyopathy (ATTR-CM) in adults.
MECHANISM OF ACTION
Acoramidis works as a transthyretin (TTR) stabilizer. It binds selectively to the thyroxine-binding sites of the transthyretin tetramer in the blood, which prevents the tetramer from dissociating into monomers. This is crucial because the misfolding of TTR monomers leads to the formation of amyloid fibrils, which accumulate in the heart and other tissues, causing transthyretin-mediated cardiomyopathy (ATTR-CM).
PHARMACOKINETICS
Absorption
Acoramidis is administered orally and is well absorbed from the gastrointestinal tract. Peak blood levels are typically reached within a few hours after ingestion. Food may slightly affect absorption, but it can generally be taken with or without meals.
Distribution
Acoramidis is widely distributed in the body after absorption and binds extensively to plasma proteins, primarily transthyretin. Its distribution helps target the drug to tissues affected by amyloid deposition, such as the heart.
Metabolism
Acoramidis is minimally metabolized the liver. Most of the drug remains unchanged in the bloodstream, allowing it to effectively stabilize transthyretin without producing significant active or toxic metabolite.
Elimination
Acoramidis is primarily excreted unchanged in the feces, with only a small portion eliminated via the urine. Its elimination half-life supports twice-daily oral dosing to maintain effective blood levels.
PHARMACODYNAMICS
Acoramidis stabilizes the transthyretin (TTR) tetramer, preventing its dissociation into monomers that can misfold and form amyloid fibrils. By reducing amyloid formation, it slows the progression of transthyretin-mediated cardiomyopathy (ATTR-CM), improves cardiac structure and function, and lowers the risk of cardiovascular-related hospitalizations and death
ADMINISTRATION
Acoramidis is taken orally as tablets, with a typical dose of 712 mg twice daily. It can be taken with or without food, and consistent dosing at the same times each day helps maintain effective blood levels.
DOSAGE AND STRENGTH
Strength: 356 mg per tablet
Recommended Dose: 712 mg twice daily (two tablets per dose)
Route: Oral
DRUG INTERACTIONS
Acoramidis can interact with drugs that affect liver enzymes, particularly CYP3A4 and other pathways involved in metabolism, although it is minimally metabolized. Concomitant use with strong enzyme inhibitors or inducers may alter acoramidis blood levels.
FOOD INTERACTIONS
Acoramidis can be taken with or without food, and meals do not significantly affect its absorption or effectiveness.
CONTRAINDICATIONS
Acoramidis is contraindicated in patients with a known hypersensitivity to the drug. Caution is advised in individuals with severe liver impairment, and it is not approved for use in children.
SIDE EFFECTS
Diarrhea
Upper abdominal pain
Nause
TOXICITY
Current data indicate that acoramidis has a favorable safety profile, with no major organ toxicity reported at therapeutic doses. Overdose may increase the risk of gastrointestinal side effects like diarrhea or abdominal discomfort, but serious toxic effects are rare.
