ATTRUBY 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.

ATTRUBY is available as 356 mg acoramidis, white, film-coated, oval tablets, printed with the BridgeBio company logo followed by “ACOR” in black ink on one side.

None.

There is no clinical experience with overdose. In case of suspected overdose, treatment should be symptomatic and supportive.

ATTRUBY contains 356 mg acoramidis equivalent to 400 mg acoramidis HCl.

Acoramidis HCl is a transthyretin stabilizer. The chemical name of acoramidis HCl is 3-[3-(3,5-dimethyl-1H-pyrazol-4-yl)propoxy]-4-fluorobenzoic acid hydrochloride. The molecular formula is C

Acoramidis HCl is a white to tan solid. The solubility of acoramidis is ≥ 12 micrograms/mL from pH 1.2 to 6.8 in aqueous media.

ATTRUBY is supplied as a white, film-coated, oval tablet, contains 356 mg acoramidis, printed with the BridgeBio company logo followed by “ACOR” in black ink on one side.

The inactive ingredients are croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and silicon dioxide. The film coating and printing ink contain black iron oxide, glyceryl monocaprylocaprate, hypromellose, polyvinyl alcohol, propylene glycol, talc, titanium dioxide, and vinyl alcohol graft copolymer.

The efficacy of ATTRUBY was demonstrated in a multicenter, international, randomized, double-blind, placebo-controlled study in 611 adult patients with wild-type or variant (hereditary or

Participants were randomized (2:1) to receive ATTRUBY 712 mg (n=409) or placebo (n=202) twice daily for 30 months. Treatment assignment was stratified by type of ATTR-CM [variant (ATTRv-CM) or wild-type (ATTRwt-CM)], NT-proBNP level, and estimated glomerular filtration rate (eGFR). The mean age of study participants was 77 years, 90.8% were male, 87.9% were White, 4.7% Black or African American, 2.1% Asian, 5.3% race other, 19% had a history of permanent pacemaker and 58% had a history of atrial fibrillation. No significant imbalance in baseline characteristics was observed between the two treatment groups.

Participants were permitted to initiate open-label tafamidis after 12 months in the study. A total of 107 participants received tafamidis: 61 (14.9%) in the ATTRUBY arm and 46 (22.8%) in the placebo arm. The median time to initiation of tafamidis for these 107 participants was 17 months.

The primary composite endpoint included all-cause mortality (ACM) and cumulative frequency of cardiovascular-related hospitalizations (CVH) over 30 months, analyzed hierarchically using the stratified Finkelstein-Schoenfeld (F-S) test. The F-S test demonstrated a statistically significant reduction (p=0.018) in ACM and cumulative frequency of CVH in the ATTRUBY arm versus the placebo arm. All-cause mortality was reported in 19% and 26% of participants in the ATTRUBY and placebo groups, respectively. The majority (79%) of the deaths were cardiovascular. CVH was reported in 27% and 43% of participants in the ATTRUBY and placebo groups, respectively. The mean number of CVH events was 0.3 vs 0.6 per year. The majority (59%) of CVH were heart failure hospitalizations reported in 13% and 26% of the participants in the ATTRUBY and placebo groups, respectively.

The treatment effect of ATTRUBY on functional capacity and health status was assessed by the 6MWD and the Kansas City Cardiomyopathy Questionnaire-Overall Summary score (KCCQ-OS) respectively. At month 30, the LS mean difference (95% CI) in change from baseline in 6MWD was 40 [21, 58] meters (p < 0.0001) and change from baseline in KCCQ-OS was 10 [6, 14] points (p < 0.0001) (

   Abbreviations: 6MWD = Six-Minute Walk Distance; KCCQ-OS = Kansas City Cardiomyopathy Questionnaire Overall Summary Score; SE = standard error; LS = least squares.

   The changes from baseline in 6MWT and KCCQ-OS were analyzed using the mixed model for repeated measures (MMRM) with treatment group, visit, genotype (ATTRv-CM vs ATTRwt-CM), NT-proBNP level (≤ 3000 vs > 3000 pg/mL), eGFR level (≥ 45 vs < 45 mL/min/1.73 m

A Cox regression analysis indicated a 35.5% decrease in the risk of the composite of ACM or first CV hospitalization (hazard ratio: 0.645 [95% CI: 0.500, 0.832]). A Kaplan-Meier plot of time to first event of ACM or CVH is shown in

   Abbreviations: ATTR-CM = transthyretin amyloid cardiomyopathy; ATTRv-CM = variant ATTR-CM; ATTRwt-CM = wild-type ATTR-CM; eGFR = estimated glomerular filtration rate; mITT = modified intent-to-treat; NAC = National Amyloidosis Centre; NT-proBNP = N-terminal prohormone of brain natriuretic peptide; NYHA = New York Heart Association

ATTRUBY (acoramidis) tablets, 356 mg, are white, film-coated, oval tablets, printed with the BridgeBio company logo followed by “ACOR” in black ink on one side.

ATTRUBY tablets are supplied as a carton of 112 tablets: 4 blister cards (each containing 28 tablets)– (NDC 82228-712-28).

Store ATTRUBY at controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)

Advise the patient to read the FDA-approved patient labeling (Patient Information).