Efficacy Data VYNDAMAX (tafamidis)

VYNDAMAX improves survival and helps keep patients out of the hospital vs placebo¹

Primary composite endpoint: VYNDAQEL^® (tafamidis meglumine) significantly reduced the combination of all-cause mortality and CV-related hospitalizations vs placebo over 30 months, p=0.0006.^1‡

Patients alive at month 30^1§||

Average CV-related hospitalizations per patient per year during 30 months^1||

Averages below are from the 287 patients alive at month 30.

All-cause mortality as an individual component: VYNDAQEL significantly reduced the risk of all-cause mortality vs placebo, p=0.026 at month 30.^1,3,4

All-cause mortality at month 30^1,3,4§||

~80% of total deaths were CV-related in both treatment groups¹

~80% of total deaths were CV-related in both treatment groups¹

CV-related hospitalizations as an individual component: VYNDAQEL significantly reduced the risk of frequency of CV-related hospitalizations vs placebo, p<0.0001 at month 30.^1,3,4

CV-related hospitalization frequency during 30 months^1,3||

~4 patient-years of treatment are needed to prevent 1 CV-related hospitalization⁴

Study endpoints overview

Statistical analysis of individual components of the primary analysis overview¹: 

The components of the primary analysis, all-cause mortality and CV-related hospitalizations, were evaluated individually. All-cause mortality was analyzed with the use of a Cox proportional-hazards model, with treatment and the stratification factors treated as covariates. The CV-related hospitalization analysis was based on a Poisson regression model with treatment, transthyretin (TTR) status (hereditary and wild-type), New York Heart Association (NYHA) baseline class (NYHA classes I and II combined versus NYHA Class III), treatment-by-TTR genotype interaction, and treatment-by-NYHA baseline classification interaction terms as factors.

VYNDAMAX has a Class 1 recommendation for ATTR cardiac amyloidosis in the 2022 AHA/ACC/HFSA Guidelines⁵

VYNDAMAX is recommended for ATTR cardiac amyloidosis in the ACC 2025 Concise Clinical Guidance⁶

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Primary analysis determined by the Finkelstein-Schoenfeld method, a hierarchical combination of both components, prioritizing all-cause mortality.^1,3

Heart transplantation, combined heart and liver transplantation, and cardiac mechanical assist device implantation are treated as equivalent to death in this analysis.^1,3

Individual components of the primary analysis.¹

6MWT=6-minute walk test; ACC=American College of Cardiology; AHA=American Heart Association; ATTR=transthyretin amyloidosis; ATTR-ACT=The Transthyretin Amyloidosis Cardiomyopathy Clinical Trial; CI=confidence interval; CV=cardiovascular; HFSA=Heart Failure Society of America; HR=hazard ratio; KCCQ-OS=Kansas City Cardiomyopathy Questionnaire-Overall Summary; NNT=number needed to treat.

References:

VYNDAQEL and VYNDAMAX [prescribing information]. New York, NY: Pfizer Inc; 2023.

Lockwood PA, Le VH, O’Gorman MT, et al. The bioequivalence of tafamidis 61-mg free acid capsules and tafamidis meglumine 4 x 20-mg capsules in healthy volunteers. Clin Pharmacol Drug Dev. 2020;9(7):849-854.

Maurer MS, Schwartz JH, Gundapaneni B, et al; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016.

Maurer MS, Mann DL. The tafamidis drug development program: a translational triumph. JACC Basic Transl Sci. 2018;3(6):871-873.

Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032.

Kittleson MM, Ambardekar AV, Cheng RK, et al. Transthyretin cardiac amyloidosis evaluation and management: 2025 ACC concise clinical guidance. J Am Coll Cardiol. Published online October 31, 2025. doi:10.1016/j.jacc.2025.09.004

ATTR-ACT

VYNDAMAX demonstrated benefits in functional capacity and health-related quality of life vs placebo¹

6MWT

The 6MWT evaluates patients’ functional capacity by measuring the distance walked in  6 minutes. LS mean (SE) change in distance walked on the 6MWT from baseline to month 30 was a predefined secondary endpoint of ATTR-ACT (pooled VYNDAQEL, n=264; placebo, n=177; p<0.0001). Average distance walked at month 30 was 296 m for pooled VYNDAQEL, and 222 m for placebo.^1,3

KCCQ-OS

The KCCQ-OS score assesses patient health status using the following domains: total symptoms (symptom frequency, symptom burden), physical limitation, QoL, and social limitation. LS mean (SE) change from baseline to month 30 in the KCCQ-OS score was a predefined secondary endpoint of ATTR-ACT. KCCQ-OS scores range from 0 to 100, with lower scores denoting poorer QoL. Average change in KCCQ-OS score for pooled VYNDAQEL was -7, and -21 for placebo.^1,3

Key secondary endpoint overview: the treatment effect of tafamidis on functional capacity and health status was assessed by the 6MWT and KCCQ-OS score, respectively. Both key secondary endpoints evaluated change from baseline to month 30.³

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6MWT=6-minute walk test; ATTR-ACT=The Transthyretin Amyloidosis Cardiomyopathy Clinical Trial; KCCQ-OS=Kansas City Cardiomyopathy Questionnaire-Overall Summary; LS=least squares; QoL=quality of life; SE=standard error.

References:

VYNDAQEL and VYNDAMAX [prescribing information]. New York, NY: Pfizer Inc; 2023.

Maurer MS, Schwartz JH, Gundapaneni B, et al; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016.

Spertus JA, Jones PG, Sandhu AT, Arnold SV. Interpreting the Kansas City Cardiomyopathy Questionnaire in clinical trials and clinical care: JACC state-of-the-art review. J Am Coll Cardiol. 2020;76(20):2379-2390.

Elliott P, Drachman BM, Gottlieb SS, et al. Long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy. Circ Heart Fail. 2022;15(1):e008193.

Data on file. Pfizer Inc., New York, NY.