Acoramidis: oral TTR stabiliser in ATTR cardiomyopathy
Acoramidis (brand name Attruby in the US, Beyonttra in the EU) is an oral high affinity stabiliser of the plasma protein transthyretin (TTR). It was approved in 2024 in the US and 2025 in the EU for the treatment of wild type or hereditary transthyretin amyloidosis with cardiomyopathy (ATTR CM) in adults. ATTR CM is a rare but increasingly recognised cause of heart failure with preserved ejection fraction (HFpEF), particularly in older patients.
With acoramidis a second TTR stabiliser became available after tafamidis. The pivotal phase 3 ATTRibute CM trial showed a significant reduction of cardiovascular hospitalisations versus placebo and a trend toward reduced overall mortality.
Mechanism of action
Transthyretin (TTR) is a tetrameric protein produced in the liver that transports thyroxine and retinol binding protein in the blood. In transthyretin amyloidosis the tetramer dissociates into monomers that misfold and aggregate into amyloid fibrils. These fibrils deposit in tissue, particularly in the heart (ATTR CM) and in peripheral nerves (ATTR polyneuropathy), causing progressive functional impairment.
Acoramidis binds with high affinity to the thyroxine binding pockets of the tetramer and stabilises it against dissociation. Formation of amyloidogenic monomers is reduced and amyloid deposition slows. Compared with tafamidis, acoramidis binds more strongly and produces higher TTR stabilisation in in vitro studies.
Acoramidis is absorbed orally and metabolised through several pathways. The half life allows twice daily dosing.
Indications
- Wild type transthyretin amyloidosis with cardiomyopathy (wtATTR CM): the more common form, particularly in older men
- Hereditary transthyretin amyloidosis with cardiomyopathy (vATTR CM): various TTR mutations with different clinical presentations
- Off label or in trials: ATTR polyneuropathy, mixed forms
Therapy requires confirmed ATTR amyloidosis (histology or imaging with DPD or PYP scintigraphy). Differentiation between wild type and hereditary form is made by TTR sequencing.
Dosing and administration
Standard dose: 712 mg orally twice daily, about 12 hours apart. Take regardless of meals.
Tablets are swallowed whole with water. With a missed dose take the next dose at the regular time, do not double dose.
Therapy is designed for long term use. Treatment success is assessed clinically (symptoms, NYHA class, 6 minute walk), biochemically (NT proBNP, troponin) and on cardiac imaging (echocardiography, cardiac MRI).
Adverse effects
Common: diarrhoea, abdominal pain, flatulence.
Uncommon: nausea, mild rise in liver transaminases, rash.
Rare: severe allergic reactions, hepatitis.
Overall acoramidis has a favourable tolerability profile. The most common gastrointestinal complaints typically appear at the start and often improve over time.
Important points:
- Persistent gastrointestinal complaints: symptomatic treatment and dietary advice if needed
- Liver enzymes before therapy and periodically thereafter
- Acute heart failure deterioration or symptom progression: cardiology re evaluation
Interactions
- Thyroid hormones: acoramidis binds in the thyroxine binding pockets of TTR. Thyroid hormone binding in blood may change; clinical relevance is usually minor, but check TSH and free T4 if abnormalities appear
- Vitamin A (retinol binding protein): retinol levels may be slightly raised
- Other agents: clinically relevant interactions rarely described so far
Special considerations
Pregnancy: data limited; individual evaluation with clear indication. Women of childbearing potential should use reliable contraception, since animal data are insufficient.
Breastfeeding: no data.
Children: not approved.
Indication: requires confirmed ATTR CM. With suspicion diagnosis is made in specialised amyloidosis centres with echocardiography, cardiac MRI, DPD or PYP scintigraphy and possibly biopsy.
Follow up: clinical and cardiology assessment every 3 to 6 months. Echocardiography and biochemical markers (NT proBNP, troponin) for monitoring. Genetic counselling for hereditary form.
Patient communication: ATTR CM is a chronic disease. Acoramidis slows progression but cannot reverse existing damage. Early therapy after diagnosis improves prognosis. Realistic information about long term nature of therapy and importance of adherence is important.
Related substances
- Tafamidis, established TTR stabiliser
- Clopidogrel, cardiovascular prevention
- Dabigatran etexilate, DOAC in atrial fibrillation in ATTR CM
- Aflibercept, another recombinant agent in chronic disease
Frequently asked questions
What is ATTR CM?
Transthyretin amyloidosis with cardiomyopathy is a progressive disease in which amyloid fibrils from misfolded TTR protein deposit in heart muscle. The result is wall thickening, impaired diastolic function and heart failure. The wild type form mostly affects older men; the hereditary form can present earlier and with polyneuropathy.
How does acoramidis differ from tafamidis?
Both stabilise TTR and slow progression of ATTR CM. Acoramidis binds the thyroxine pockets more strongly and produces higher in vitro stabilisation. Direct head to head clinical comparisons are largely absent; both agents are established options.
Does acoramidis cure the disease?
No. Acoramidis slows the progression of amyloid deposition but cannot reverse existing damage. Early therapy after diagnosis is therefore important.
How is ATTR CM diagnosed?
With clinical suspicion (HFpEF, low voltage ECG, right heart failure, bilateral carpal tunnel syndrome in history) diagnosis is by echocardiography, cardiac MRI, DPD or PYP scintigraphy and genetics. Endomyocardial biopsy is rarely required today.
Sources
- EMA European Medicines Agency
- BfArM German Federal Institute for Drugs and Medical Devices
- AWMF guidelines heart failure and amyloidosis
- Gelbe Liste acoramidis monograph
Legal notice and disclaimer
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