Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy

Phase 3, multicenter, global, three-arm, parallel design, placebo-controlled, double-blind,
randomized study to determine efficacy, safety and tolerability of tafamidis on clinical
outcomes (all-cause mortality and frequency of cardiovascular-related hospitalizations) in
subjects with either transthyretin genetic variants or wild-type transthyretin resulting in
amyloid cardiomyopathy.

Inclusion Criteria:

- Medical history of Heart Failure (HF) with at least 1 prior hospitalization for HF or
clinical evidence of HF (without hospitalization) manifested by signs or symptoms of
volume overload or elevated intracardiac pressures (e.g., elevated jugular venous
pressure, shortness of breath or signs of pulmonary congestion on x-ray or
auscultation, peripheral edema) that required/requires treatment with a diuretic for
improvement,

- Evidence of cardiac involvement by echocardiography with an end-diastolic
interventricular septal wall thickness > 12 mm,

- Presence of amyloid deposits in biopsy tissue and presence of a variant TTR genotype
and/or TTR precursor protein identification by immunohistochemistry, scintigraphy or
mass spectrometry

Exclusion Criteria:

- A New York Heart Association (NYHA) classification of IV.

- Presence of primary (light chain) amyloidosis.

- Prior liver or heart transplantation or implanted cardiac mechanical assist device.