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    Study Design

    Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT)—a clinical study in patients with ATTR-CM1

    Approval of VYNDAMAX was based on ATTR-ACT, a phase 3, multicenter, international, randomized, double-blind, placebo-controlled study, which evaluated pooled VYNDAQEL® (tafamidis meglumine) doses of 20 mg and 80 mg in 441 patients with wild-type or hereditary ATTR-CM—a single VYNDAMAX 61-mg capsule is bioequivalent* to VYNDAQEL 80 mg (four 20-mg capsules) and is not interchangeable on a per-mg basis.

    ** This is an optional area where footnotes can live.

    Two-thirds of patients in the pooled VYNDAQEL group were on the 80-mg dose.​​​​​​​

       *As determined by the predefined 90% confidence interval criteria of 80%-125% bioequivalence limits for tafamidis area under curve (AUC) and peak plasma concentration (Cmax) after repeated oral daily dosing for 7 days.2​​​​​​​

        ‡The primary analysis was conducted using the Finkelstein-Schoenfeld method.​​​​​​​

    Inclusion criteria1

    • Patients between 18 and 90 years of age
    • Confirmation of ATTR-CM, wild-type or hereditary
    • Echocardiography with an end-diastolic interventricular septal wall thickness >12 mm
    • History of heart failure with at least 1 prior hospitalization for heart failure, or clinical evidence of heart failure (without hospitalization)§
    • NT-proBNP level ≥600 pg/mL
    • 6MWT >100 m

       §Manifested in signs or symptoms of volume overload or elevated intracardiac pressures requiring treatment with a diuretic for improvement; an N-terminal pro-B-type natriuretic peptide (NT-proBNP) level greater than or equal to 600 pg per milliliter; and a 6-minute walk-test distance exceeding 100 m.
    NT-proBNP=N-terminal pro-B-type natriuretic peptide.

    Exclusion criteria1

    • Heart failure unrelated to ATTR-CM
    • NYHA class IV heart failure
    • Light-chain amyloidosis
    • History of liver or heart transplantation
    •  Implanted cardiac mechanical assist device3||
    • Previous VYNDAQEL treatment
    • eGFR <25 mL/min/1.73 m2
    • Liver transaminase levels >2x the upper limit of normal
    • mBMI <600
    • ​​Concurrent treatment with NSAIDs, tauroursodeoxycholate, doxycycline, calcium channel blockers, or digitalis

        ||Cardiac mechanical assist device (CMAD) term utilized to cover LVAD. Patients with a permanent pacemaker or implanted cardiac defibrillator were permitted in this study.

        ¶Select NSAIDs were permitted, eg, aspirin, ibuprofen, naproxen.
    ​​​​​​​eGFR=estimated glomerular filtration rate; LVAD=left ventricular assist device; mBMI=modified body mass index.
    ​​​​​​​

    The Finkelstein-Schoenfeld method1

    ​​  ​​​​​ #Frequency of CV-related hospitalizations is used to compare patients who cannot be differentiated based on all-cause mortality.

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    References:
    1. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016.
    2. Tankisheva E. A phase 1, open-label, randomized, crossover, multiple dose, pivotal bioequivalence study to compare PF-06291826 4 × 20 mg tafamidis meglumine and 61 mg: tafamidis free acid soft gelatin capsules administered under fasted conditions to healthy volunteers. Full Clinical Study Report [protocol B3461056]. July 23, 2018.
    3. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy [protocol]. N Engl J Med. 2018;379(11):1007-1016. https://nejm.org/doi/suppl/10.1056/NEJMoa1805689/suppl_file/nejmoa1805689_protocol.pdf. Accessed July 2, 2019.
    4. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy [supplemental appendix]. N Engl J Med. 2018;379(11):1007-1016. https://nejm.org/doi/suppl/10.1056/NEJMoa1805689/suppl_file/nejmoa1805689_appendix.pdf. Accessed July 1, 2019.

    About

    • About ATTR-CM
    • MOD/MOA
    • Study Design

    Efficacy and safety outcomes

    Review the clincal data


    VYNDAMAX® AND VYNDAQEL® are registered trademarks of Pfizer Inc.

    Adverse Reactions

    In studies in patients with ATTR-CM, the frequency of adverse events in patients treated with VYNDAQEL® (tafamidis meglumine) was similar to placebo.

    Specific Populations

    Pregnancy: Based on findings from animal studies, VYNDAQEL and VYNDAMAX may cause fetal harm when administered to a pregnant woman.

    Lactation: There are no available data on the presence of tafamidis in human milk, the effect on the breastfed infant, or the effect on milk production. Tafamidis is present in rat milk. When a drug is present in animal milk, it is likely the drug will be present in human milk. Breastfeeding is not recommended during treatment with VYNDAQEL and VYNDAMAX.

    VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.
    ​​​​​​​
    Please see Full Prescribing Information including Patient Information.

      INDICATION AND LIMITATIONS OF USE

      VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.
      ​​​​​​​
      Please see Full Prescribing Information including Patient Information.