Acoramidis

Acoramidis

• AG-10
• 1446711-81-4
• AG10
• Acorami

292.30 g/mol,
C₁₅H₁₇FN₂O₃

3-[3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy]-4-fluorobenzoic acid

• 3-[3-(3,5-Dimethyl-1h-Pyrazol-4-Yl)propoxy]-4-Fluorobenzoic Acid
• UNII-T12B44A1OE

FDA APPROVED 11/22/2024, Attruby To treat cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis
Drug Trials Snapshot

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]

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][9] and in the European Union in February 2025.^[2][3]

PATENTS

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US9169214	No	2015-10-27	2031-05-05
US9913826	No	2018-03-13	2033-03-14
US11058668	No	2021-07-13	2039-03-22
US10842777	No	2020-11-24	2031-05-05
US11919865	No	2024-03-05	2038-02-16
US12070449	No	2024-08-27	2039-03-22
US12005043	No	2024-06-11	2039-08-16
US10398681	No	2019-09-03	2031-05-05
US9642838	No	2017-05-09	2031-05-05
US8877795	No	2014-11-04	2031-05-05

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US10513497	No	2019-12-24	2038-02-16
US11260047	No	2022-03-01	2039-08-16

SYN

Penchala SC, Connelly S, Wang Y, Park MS, Zhao L, Baranczak A, Rappley I, Vogel H, Liedtke M, Witteles RM, Powers ET, Reixach N, Chan WK, Wilson IA, Kelly JW, Graef IA, Alhamadsheh MM: AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9992-7. doi: 10.1073/pnas.1300761110. Epub 2013 May 28

PATENT

https://patents.google.com/patent/US9913826B2/en

Chemical Synthesis

Methyl 3-(3-bromopropoxy)-4-fluorobenzoate (Compound 2)

To a solution of methyl 4-fluoro-3-hydroxybenzoate 1 (3.0 g, 17.6 mmol, 1 equiv) and 1,3-dibromopropane (9.0 ml, 88.2 mmol, 5 equiv) in DMF (40 ml) was added K₂CO₃ (2.93 g, 21.2 mmol, 1.2 equiv). The reaction mixture was stirred at room temperature for 16 hours. The mixture was diluted with EtOAc (1.5 L), washed with brine (3×0.5 L) and dried with Na₂SO₄. The solution was filtered and concentrated. The residue was purified by flash column chromatography (silica gel, 1-10% EtOAc/hexanes) to afford compound 2 (4.21 g, 82% yield); ¹H NMR (CD3OD, 600 MHz) δ 7.67-7.61 (m, 2H), 7.14-7.07 (m, 1H), 4.21 (t, 2H, J=5.89 Hz), 3.89 (s, 3H), 3.62 (t, 2H, J=6.38 Hz), 2.38-2.31 (m, 2H); (ESI⁺) m/z: calcd for C₁₁H₁₂BrFO₃+H⁺290.00; found 290.01 (M+H⁺).Methyl 3-(3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzoate (Compound 4)

A solution of 2 (780 mg, 2.69 mmol, 1 equiv) in benzene (3 ml) was added dropwise to a solution of acetyl acetone (0.552 ml, 5.38 mmol, 2 equiv) and DBU (0.804 ml, 5.38 mmol, 2 equiv) in benzene (7 ml). The reaction mixture was stirred at room temperature for 3 days. The mixture was filtered and concentrated. The residue was purified by flash column chromatography (silica gel, 1-10% EtOAc/hexanes) to afford compound 3 which was used in the next step directly. Hydrazine hydrate (0.36 ml, 6.73 mmol, 2.5 equiv) was added to a solution 3 in ethanol (5 ml) and the reaction was heated under reflux for 4 hours. The reaction was concentrated and purified by flash column chromatography (silica gel, 1-20% MeOH/CH₂Cl₂) to afford compound 4 (288 mg, 35% yield) in two steps; ¹H NMR (CD₃OD, 600 MHz) δ 7.64-7.58 (m, 2H), 7.20-7.15 (m, 1H), 4.01 (t, 2H, J=6.0 Hz), 3.86 (s, 3H), 2.58 (t, 2H, J=7.2 Hz), 2.12 (s, 6H), 1.97-1.92 (m, 2H); HRMS (DART) m/z: calcd for C16H19FN2O+H⁺307.1458; found 307.1452 (M+H⁺).3-(3-(3,5-Dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzoic acid (Compound VIIc)

To a suspension of 4 (100 mg, 0.33 mmol, 1 equiv) in a mixture of THF (3 ml) and water (3 ml) was added LiOH.H₂O (27.5 mg, 0.66 mmol, 2 equiv). The reaction mixture was stirred at room temperature for 14 hr after which it was cooled to 0° C. and carefully acidified to pH 2-3 with IN aqueous HCl. The mixture was extracted with EtOAc (3×30 ml) and the combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was subjected to flash column chromatography (silica gel, 10-50% MeOH/CH₂Cl₂) to give Compound VIIc (68 mg, 71% yield) as a white solid (>98% purity by HPLC); ¹H NMR (CD₃OD, 600 MHz) δ 7.65-7.58 (m, 2H), 7.20-7.14 (m, 1H), 4.00 (t, 2H, J=6.0 Hz), 2.58 (t, 2H, J=5.8 Hz), 2.12 (s, 6H), 1.97-1.92 (m, 2H); HRMS (DART) m/z: calcd for C15H17FN2O3+H⁺ 293.1301; found 293.1293 (M+H⁺).3-(3-(3,5-Dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzamide

To a suspension of 4 (100 mg, 0.33 mmol, 1 equiv) in a mixture of THF (3 ml) and water (3 ml) is added (23.1 mg, 0.66 mmol, 2 equiv) of NH₄OH. The reaction mixture is stirred at room temperature for 14 hr after which it is cooled to 0° C. and carefully adjusted to pH 7 with IN aqueous HCl. The mixture is extracted with EtOAc (3×30 ml) and the combined organic extracts are dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product is subjected to flash column chromatography (silica gel, 10-50% MeOH/CH₂Cl₂) to give 3-(3-(3,5-Dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzamide.N-ethyl 3-(3-(3,5-Dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzamide

To a suspension of 4 (100 mg, 0.33 mmol, 1 equiv) in a mixture of THF (3 ml) and water (3 ml) is added (27.1 mg, 0.66 mmol, 2 equiv) of C₂H₅NH₂. The reaction mixture is adjusted to pH 9.0 with 0.5N NaOH, then stirred at room temperature for 14 hr after which it is cooled to 0° C. and carefully adjusted to pH 7 with IN aqueous HCl. The mixture is extracted with EtOAc (3×30 ml) and the combined organic extracts are dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product is subjected to flash column chromatography (silica gel, 10-50% MeOH/CH₂Cl₂) to give N-ethyl 3-(3-(3,5-Dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzamide.

PATENT

https://patents.google.com/patent/US10513497B2/en

Example 1Preparation of 3-(3-Hydroxy-propyl)-pentane-2, 4-dione (a Compound of Formula IV)

A compound of Formula IIIa (100 g, 495 mmol 1.0 equiv.) was dissolved in acetone (1 L). A compound of Formula II (49.59 g, 495 mmol, 1.0 equiv.) was added to above solution, followed by addition of K₂CO₃ (82.14 g, 594.38 mmol, 1.2 equiv.) and KI (41.11 g, 247 mmol, 0.5 equiv.) at room temperature with stirring. The reaction mixture was heated to 60±5° C. and stirred for 40 h at this temperature. The reaction mixture was filtered and then concentrated under reduced pressure to afford a compound of Formula IV (102 g) as viscous orange liquid.Example 2Preparation of 3(3, 5-Dimethyl-1H-pyrazol-4-yl) propane-1-ol (a compound of Formula V)

A compound of Formula IV (100 g, 632 mmol, 1.0 equiv.) was dissolved in ethanol (1 L). Hydrazine hydrate (87 g, 1738 mmol, 2.75 equiv.) and conc. HCl (4.6 mL, 0.2 equiv.) were added to above solution at room temperature. The reaction mixture was heated to 75±5° C. and stirred for 3 h at this temperature. After completion of reaction by TLC (70% ethyl acetate: n-hexane, visible in iodine) and observation of product peak in mass spectrum, the reaction mixture was concentrated under reduce pressure to afford a compound of Formula V (70 g) as a colorless liquid syrup which was used as such for next step.Example 3Preparation of 4-(3-Bromo-propyl)-3, 5-dimethyl-1H-pyrazole (a compound of formula VIa)

A compound of Formula V (35 g, 227 mmol, 1.0 equiv.) was dissolved in 1,2-dichloroethane (525 mL). PBr₃ (64.67mL, 681 mmol, 3 equiv.) was added in small portions at room temperature over 30 minutes. The reaction mixture was heated up to 75±5° C. and stirred for 3 h at this temperature. After completion of reaction by TLC (50% ethyl acetate: n-hexane, visible in iodine) and observation of product peak in Mass spectrum, the reaction mixture was diluted with dichloromethane (350 mL) and quenched with saturated solution of NaHCO₃ till pH=7 to 8. Both organic and aqueous layers were separated and collected. The organic layer was dried over MgSO₄ and filtered. Filtrate was concentrated under reduce pressure to afford a compound of Formula VIa (38 g) as a viscous orange liquid.Example 4Preparation of 3-[3-(3, 5-Dimethyl-1H-pyrazol-4-yl)-propoxy]-4-fluoro-benzoic acid methyl ester (a compound of Formula VIIIa)

A compound of Formula VIIa (19 g, 111 mmol, 1.0 equiv.) was dissolved in DMF (190 mL). A compound of Formula VIa (31.5 g, 145.14 mmol, 1.3 equiv.) was added followed by K₂CO₃ (38.6 g, 279.18 mmol, 2.5 equiv.) at room temperature under stirred conditions. The reaction mixture was stirred for 16 to 18 h at room temperature. After completion of reaction in TLC (50% ethyl acetate: n- hexane), the reaction mixture was diluted with water (190 mL) and ethyl acetate (95 mL). Both organic layer and aqueous layer were separated and collected. Aqueous layer was extracted with ethyl acetate (190 mL). The combined organic extract was washed with water (95 mL), brine (95 mL), dried over Na₂SO₄ and filtered. The filtered organic layer was concentrated under reduce pressure to afford a crude viscous orange liquid (40 g). The crude was further purified by column chromatography using silica gel (285 g) and eluted with varying quantity of ethyl acetate in hexane to afford pure product, a compound of Formula VIIIa (25 g) as an off white solid.Example 5Preparation of 3-[3-(3,5-Dimethyl-1H-pyrazol-4-yl)-propoxy]-4-fluoro-benzoic acid methyl ester (a compound of Formula VIIIa)

4-(3-Bromopropyl)-3,5-dimethyl-1H-pyrazole hydrobromide (VIa) and DMSO were charged into vessel and agitated at 20±10° C. for 10 minutes. The mixture was then heated to 55±5° C. with stirring. To this mixture was transferred a stirred solution containing 4-fluoro-3-hydroxy-benzoic acid methyl ester (VIIa), potassium carbonate and anhydrous DMSO. The DMSO solution of the alkyl bromide were slowly transferred in order to maintaining an internal temperature of 55.0±5° C. Addition was complete after 6 hours and the mixture was agitated at 55.0±5° C. for an additional hour at 55.0±5° C. The mixture was cooled to 25±5° C. over the course of 30 minutes and water added while maintaining a temperature below 25° C. The mixture was extracted with ethyl acetate and the aqueous layer back extracted with ethyl acetate. The pooled ethyl acetate solutions were washed brine. The combined ethyl acetate washes were concentrated under vacuum to a minimal volume and heptane was added, which precipitates VIIIa. The mixture was heated to 75±5° C. and aged with stirring for 1 hour. The mixture was cooled to 25±5° C. over the course of two hours and the resulting solids collected by filtration. The filter cake was washed with ethyl acetate in heptane (30%). Isolated solids were dried with a nitrogen flow. Solids are charged to vessel and combined with ethyl acetate and heptane. The resulting mixture is heated to 75±5° C. to dissolve solids. The solution was cooled to 25±5° C. over the course of two hours and the resulting solids collected by filtration. The solids were washed with a 30% ethyl acetate/heptane solvent mixture and dried in vacuum oven at 55° C. to give VIIIa in >99.5% purity.Example 6Preparation of 3-[3-(3, 5-Dimethyl-1H-pyrazol-4-yl)-propoxy]-4-fluoro-benzoic acid (a compound of Formula IX)

A compound of Formula VIIIa (19 g, 62 mmol, 1 equiv.) was dissolved in methanol (95 mL, 5 vol.) at room temperature. A solution of LiOH.H₂O (6.5 g, 155 mmol, 2.5 equiv.) in water (57 mL) was added in small portions at room temperature over 10 to 15 minutes. The reaction mixture was stirred for 2 h at room temperature. After completion of reaction by TLC (70% ethyl acetate: n-hexane), the reaction mixture is concentrated below 45° C. under reduced pressure to afford a solid residue of Formula IX.Example 7Preparation of a Pharmaceutically Acceptable Salt of Formula I

The solid residue of Formula IX was dissolved in water (57 mL) and stirred for 10 min and cooled to 0±5° C. The aqueous solution was acidified with conc. HCl (20-25 mL) to pH=2 and stirred for 30 minutes at 0±5° C. Precipitation was observed which was filtered and dried at room temperature to afford pure product, a compound of Formula Ia (17.5 g) as an off-white solid.Example 8Additional Preparation of a Pharmaceutically Acceptable Salt of Formula I

Water and concentrated HCl were charged to a vessel and cooled with stirring to 10±5° C. Compound of Formula IX and water were charged to a second vessel and cooled with stirring to 10±5° C. The HCl solution in vessel

 1 was transferred to a vessel containing compound of Formula IX mixture over not less than 15 minutes, while maintaining a temperature of <25° C. The resulting slurry was aged with stirring at 20±5° C. for 44 hours. The solids were collected by filtration, washed with 0.2 N HCl (3 ×) and dried under vacuum at ≥55° C. to provide Ia as white solid, >99.8% purity.Example 9Preparation of 3-[3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy]-4-fluorobenzoic acid hydrochloride salt (Compound Ia) from VIIIa

A jacketed glass vessel is charged with compound of formula VIIIa (1.0 equiv.) and methanol. The mixture is cooled with stirring to 10±5° C. and over the course of 20 minutes an aqueous solution of sodium hydroxide (3 equiv.) is charged. The mixture is aged with stirring at 20±5° C. for NLT

 2 hours at which point the reaction is complete. Stirring is stopped and water is added. Methanol is then removed by vacuum distillation at an internal temperature of NMT

 35° C. The resulting concentrated, clear aqueous solution is cooled to 10° C. and concentrated HCl is added until the pH was lowered to between 1.4-1.6 (pH meter) to precipitate the HCl salt. The solids are collected by filtration, washed with 0.2 N HCl and dried under vacuum at 50° C. to give a compound of Formula Ia in NLT 99.5% purity.Example 10Preparation of 3-[3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy]-4-fluorobenzoic acid (compound of formula IX) from VIIIa

Methyl 3-(3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy)-4-fluorobenzoate (Compound of formula VIIIa) and methanol were charged into a vessel and the resulting mixture was agitated at 20±5° C. until dissolved. The solution was cooled to 10±5° C. and over the course of 20 minutes a sodium hydroxide solution was added while maintaining a temperature ≤25° C. The mixture temperature was adjusted to 25±5° C. and aged with stirring for 18 hours. The reaction mixture was filtered. Water was added to filtrate and the resulting mixture concentrated under vacuum until volume of the mixture was reduced to minimal volume. Water was again added and the resulting mixture concentrated under vacuum until volume of the mixture was reduced to minimal volume. The pH of the aqueous mixture was adjusted to 5.5±0.5 by addition of concentrated hydrochloric acid then 0.5N HCl. The temperature of the mixture was adjusted to 7±5° C. and aged with stirring for an additional hour. The solids were collected by filtration, washed with water and partially dried under vacuum at ≥55° C. to provide compound of Formula IX as white solids with >99.5% HPLC purity.Example 11Conversion of the Hydrochloride Salt to Free Base

3-[3-(3,5-Dimethyl-1H-pyrazol-4-yl)-propoxy]-4-fluorobenzoic acid hydrochloride (10.0 g, 30.4 mmol, 1.0 equiv.) was taken in deionized water (30.0 mL) at room temperature and was cooled to 10±5° C. To this mixture was added saturated sodium bicarbonate to pH≅6-7 and stirred for 30 minute at this temperature. The off white precipitate obtained was filtered and washed with deionized water (20 mL). Solid compound was dried at room temperature to afford 3-[3-(3,5-dimethyl-1H-pyrazol-4-yl)-propoxy]-4-fluorobenzoic acid (the compound of Formula IX) (7.40 g, 83.2%) as an off-white solid.

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][10]

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.^[11]

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.^[12]

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. ^[13]

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.^[14]

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.^[15][16][17]

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.^[18]

Society and culture

Legal status

Acoramidis was approved for medical use in the United States in November 2024.^[6][7][19] The approval was granted to BridgeBio Pharma.^[10]

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).^[20]

Acoramidis is the international nonproprietary name.^[21]

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

References

1. ^ Jump up to:^{a b c d e} “Attruby- acoramidis hydrochloride tablet, film coated”. DailyMed. 26 November 2024. Retrieved 28 November 2024.
2. ^ Jump up to:^{a b c d e f g} “Beyonttra EPAR”. European Medicines Agency (EMA). 12 December 2024. Retrieved 15 December 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
3. ^ Jump up to:^a b c d “Beyonttra PI”. Union Register of medicinal products. 11 February 2025. Retrieved 16 February 2025.
4. ^ Penchala SC, Connelly S, Wang Y, Park MS, Zhao L, Baranczak A, et al. (June 2013). “AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin”. Proceedings of the National Academy of Sciences of the United States of America. 110 (24): 9992–9997. Bibcode:2013PNAS..110.9992P. doi:10.1073/pnas.1300761110. PMC 3683741. PMID 23716704.
5. ^ Miller M, Pal A, Albusairi W, Joo H, Pappas B, Haque Tuhin MT, et al. (September 2018). “Enthalpy-Driven Stabilization of Transthyretin by AG10 Mimics a Naturally Occurring Genetic Variant That Protects from Transthyretin Amyloidosis”. Journal of Medicinal Chemistry. 61 (17): 7862–7876. doi:10.1021/acs.jmedchem.8b00817. PMC 6276790. PMID 30133284.
6. ^ Jump up to:^{a b c d e f g h i j k} “FDA approves drug for heart disorder caused by transthyretin-mediated”. U.S. Food and Drug Administration. 1 October 2024. Retrieved 27 November 2024.  This article incorporates text from this source, which is in the public domain.
7. ^ Jump up to:^a b “Novel Drug Approvals for 2024”. U.S. Food and Drug Administration (FDA). 1 October 2024. Retrieved 20 December 2024.
8. ^ “FDA approves BridgeBio Pharma’s Attruby to treat rare heart disease ATTR-CM”. PMLiVE. 25 November 2024. Retrieved 25 November 2024.
9. ^ New Drug Therapy Approvals 2024 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2025. Archived from the original on 21 January 2025. Retrieved 21 January 2025.
10. ^ Jump up to:^a b LeMieux J (25 November 2024). “Bridgebio’s Attruby, to Treat Heart Condition ATTR-CM, Receives FDA Approval”. Genetic Engineering and Biotechnology News. Retrieved 25 November 2024.
11. ^ “FDA approves BridgeBio’s Attruby for ATTR-CM treatment”. Pharmaceutical Technology. 25 November 2024. Retrieved 25 November 2024.
12. ^ Fox JC, Hellawell JL, Rao S, O’Reilly T, Lumpkin R, Jernelius J, et al. (January 2020). “First-in-Human Study of AG10, a Novel, Oral, Specific, Selective, and Potent Transthyretin Stabilizer for the Treatment of Transthyretin Amyloidosis: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Adult Volunteers”. Clinical Pharmacology in Drug Development. 9 (1): 115–129. doi:10.1002/cpdd.700. PMC 7003869. PMID 31172685.
13. ^ Masri A, Aras M, Falk RH, Grogan M, Jacoby D, Judge DP, et al. (March 2022). “Long-Term Safety and Tolerability of Acoramidis (Ag10) in Symptomatic Transthyretin Amyloid Cardiomyopathy: Updated Analysis from an Ongoing Phase 2 Open-Label Extension Study”. Journal of the American College of Cardiology. 79 (9): 227. doi:10.1016/S0735-1097(22)01218-9.
14. ^ Gillmore JD, Judge DP, Cappelli F, Fontana M, Garcia-Pavia P, Gibbs S, et al. (January 2024). “Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy”. The New England Journal of Medicine. 390 (2): 132–142. doi:10.1056/NEJMoa2305434. PMID 38197816.
15. ^ “Program Planner”. http://www.abstractsonline.com. Archived from the original on 6 February 2021. Retrieved 19 October 2024.
16. ^ Alexander K, Judge D, Cappelli F, Fontana M, Garcia-Pavia P, Grogan M, et al. (6 May 2024). Acoramidis Achieves Early Reduction in Cardiovascular Death or Hospitalization in Transthyretin Amyloid Cardiomyopathy (ATTR-CM): Results from the ATTRibute-CM Clinical Trial OC7 (#281) (Report). doi:10.26226/m.65f9bf8ae6f73964e1d4f069.
17. ^ “BridgeBio Shares Recurrent Event Analysis of ATTRibute-CM, Demonstrating a 42% Reduction by Acoramidis on the Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular-related Hospitalization Events”. HFSA. Retrieved 19 October 2024.
18. ^ Ji A, Wong P, Judge DP, Graef IA, Fox J, Sinha U (November 2023). “Acoramidis produces near-complete TTR stabilization in blood samples from patients with variant transthyretin amyloidosis that is greater than that achieved with tafamidis”. European Heart Journal. 44 (Supplement_2). doi:10.1093/eurheartj/ehad655.989. ISSN 0195-668X.
19. ^ “Attruby (acoramidis), a Near Complete TTR Stabilizer (≥90%), approved by FDA to Reduce Cardiovascular Death and Cardiovascular-related Hospitalization in ATTR-CM Patients” (Press release). BridgeBio Pharma. 23 November 2024. Archived from the original on 25 November 2024. Retrieved 28 November 2024 – via GlobeNewswire.
20. ^ “FDA approves Stanford Medicine-developed drug that treats rare heart disease”. Stanford. 27 November 2024. Retrieved 29 November 2024.
21. ^ World Health Organization (2024). “International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 83”. WHO Drug Information. 38 (1). hdl:10665/378096.

Further reading

• Penchala SC, Connelly S, Wang Y, Park MS, Zhao L, Baranczak A, et al. (June 2013). “AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin”. Proceedings of the National Academy of Sciences of the United States of America. 110 (24): 9992–9997. Bibcode:2013PNAS..110.9992P. doi:10.1073/pnas.1300761110. PMC 3683741. PMID 23716704.

External links

• Clinical trial number NCT03860935 for “Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy (ATTRibute-CM)” at ClinicalTrials.gov

1. Nuvolone M, Girelli M, Merlini G: Oral Therapy for the Treatment of Transthyretin-Related Amyloid Cardiomyopathy. Int J Mol Sci. 2022 Dec 18;23(24):16145. doi: 10.3390/ijms232416145. [Article]
2. Penchala SC, Connelly S, Wang Y, Park MS, Zhao L, Baranczak A, Rappley I, Vogel H, Liedtke M, Witteles RM, Powers ET, Reixach N, Chan WK, Wilson IA, Kelly JW, Graef IA, Alhamadsheh MM: AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9992-7. doi: 10.1073/pnas.1300761110. Epub 2013 May 28. [Article]
3. Fox JC, Hellawell JL, Rao S, O’Reilly T, Lumpkin R, Jernelius J, Gretler D, Sinha U: First-in-Human Study of AG10, a Novel, Oral, Specific, Selective, and Potent Transthyretin Stabilizer for the Treatment of Transthyretin Amyloidosis: A Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Adult Volunteers. Clin Pharmacol Drug Dev. 2020 Jan;9(1):115-129. doi: 10.1002/cpdd.700. Epub 2019 Jun 6. [Article]
4. FDA Approved Drug Products: Attruby (acoramidis) tablets for oral administration (November 2024) [Link]
5. FDA News Release: FDA approves drug for heart disorder caused by transthyretin-mediated amyloidosis [Link]

/////////Acoramidis, Attruby, AG 10, AG10. AG-10, WHO 11205, APPROVALS 2024, FDA 2024