Acoramidis

Acoramidis, sold under the brand name Attruby, is a medication used for the treatment of cardiomyopathy.^[1] It is a near-complete (>90%) transthyretin stabilizer, developed to mimic the protective properties of the naturally-occurring T119M mutation,^[4][5] to treat transthyretin amyloid cardiomyopathy. It is taken by mouth.^[1]

Acoramidis

Clinical data
Pronunciation	ə-corAM-i-dis
Trade names	Attruby, others
Other names	AG10
AHFS/Drugs.com	Monograph
MedlinePlus	a625013
License data	US DailyMed: Acoramidis
Routes of administration	By mouth
Drug class	Amyloidogenesis suppressant
ATC code	C01EB25 (WHO)
Legal status
Legal status	US: ℞-only[1] EU: Rx-only[2][3]
Identifiers
IUPAC name 3-[3-(3,5-Dimethyl-1H-pyrazol-4-yl)propoxy]-4-fluorobenzoic acid
CAS Number	1446711-81-4 2242751-53-5
PubChem CID	71464713 71464713
IUPHAR/BPS	135307127
DrugBank	DB17999
ChemSpider	35033544
UNII	T12B44A1OE VY9C88C2NV
KEGG	D11972 D11973
ChEMBL	ChEMBL3940890 ChEMBL4650226
PDB ligand	16V (PDBe, RCSB PDB)
Chemical and physical data
Formula	C15H17FN2O3
Molar mass	292.310 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1=C(C(=NN1)C)CCCOC2=C(C=CC(=C2)C(=O)O)F
InChI InChI=1S/C15H17FN2O3/c1-9-12(10(2)18-17-9)4-3-7-21-14-8-11(15(19)20)5-6-13(14)16/h5-6,8H,3-4,7H2,1-2H3,(H,17,18)(H,19,20) Key:WBFUHHBPNXWNCC-UHFFFAOYSA-N InChI=1S/C15H17FN2O3.ClH/c1-9-12(10(2)18-17-9)4-3-7-21-14-8-11(15(19)20)5-6-13(14)16;/h5-6,8H,3-4,7H2,1-2H3,(H,17,18)(H,19,20);1H Key:MGFZEARHINUOMX-UHFFFAOYSA-N

The most common adverse reactions include diarrhea and upper abdominal pain.^[6]

Acoramidis was approved for medical use in the United States in November 2024,^[6][7][8] and in the European Union in February 2025.^[2][3]

Medical uses

Acoramidis is indicated for the treatment of the cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular death and cardiovascular-related hospitalization.^[1][6][9]

ATTR-CM is a rare and serious disease that affects the heart muscle.^[6] In people with ATTR-CM, there is a build-up of protein deposits in the heart, causing the walls of the heart to become stiff, and making the left ventricle unable to properly relax and fill with blood (called cardiomyopathy).^[6] As the condition progresses, the heart can become unable to pump blood out adequately, causing heart failure.^[6] There are two types of ATTR-CM, hereditary ATTR-CM (hATTR-CM) and wild-type ATTR-CM (wATTR-CM).^[6] In hATTR-CM, which can run in families, there's a variant in the transthyretin gene, which results in protein deposits in the heart. In wATTR-CM, there is no variant in the transthyretin gene.^[6]

Side effects

The most common side effects are diarrhea and abdominal pain.^[10]

History

The efficacy and safety of acoramidis were evaluated in a multicenter, international, randomized, double-blind, placebo-controlled study in 611 adult participants with wild-type or hereditary (variant) ATTR-CM (NCT03860935).^[6]

Clinical trials

Phase I data indicated acoramidis achieved near-complete (>90%) TTR stabilization across the entire dosing interval at steady state.^[11]

Phase II and the Open-Label Extension (OLE) data indicated after a median of 38 months, long-term treatment with acoramidis was generally well tolerated and resulted in a median decline in NT-proBNP levels, normalization of serum TTR, and sustained stabilization of TTR in individuals with ATTR-CM. ^[12]

Phase III data from ATTRibute-CM indicated acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo at 30 months in participants with ATTR-CM. Adverse events were similar in the two groups.^[13]

Other analyses from ATTRibute-CM indicated a 50% reduction in cumulative cardiovascular hospitalizations (CVH), a 42% reduction in all-cause mortality (ACM) and recurrent CVH, and a 3-month time-to-separation of the Kaplan Meier curves for ACM or CVH. No other treatment has demonstrated this degree of treatment effect this quickly in participants with ATTR-CM.^[14][15][16]

In vitro data indicated acoramidis exhibits near-complete (>90%) TTR stabilization at therapeutic trough concentrations, and its TTR stabilization exceeds that of tafamidis' across a range of destabilizing TTR mutations.^[17]

Society and culture

Legal status

Acoramidis was approved for medical use in the United States in November 2024.^[6][7][18] The approval was granted to BridgeBio Pharma.^[9]

In December 2024, the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Beyonttra, intended for the treatment of transthyretin amyloidosis in adults with cardiomyopathy.^[2] The applicant for this medicinal product is BridgeBio Europe B.V.^[2] Acoramidis was designated an orphan medicine by the EMA.^[2] Acoramidis was authorized for medical use in the European Union in February 2025.^[2][3]

Names

During development, acoramidis was known as AG10 (the Alhamadsheh-Graef molecule 10).^[19]

Acoramidis is the international nonproprietary name.^[20]

Acoramidis is sold under the brand names Attruby^[1][6] and Beyonttra.^[2][3]