The primary objective of this study is to access the efficacy of ALXN2220 in the treatment of adult participants with ATTR-CM by evaluating the difference between the ALXN2220 and placebo groups as assessed by the total occurrences of all-cause mortality (ACM) and cardiovascular (CV) clinical events.

Inclusion Criteria:

• Diagnosis of ATTR-CM with either wild-type or variant TTR genotype
• End-diastolic interventricular septal wall thickness ≥ 12 mm on echocardiography measured at Screening
• NT-proBNP > 2000 pg/mL at Screening
• Treatment with a loop diuretic for at least 30 days prior to Screening
• History of heart failure NYHA Class II-IV at Screening
• Life expectancy of ≥ 6 months as per the Investigator's judgment
• Males and females of childbearing ability must use contraception

Exclusion Criteria:

• Known leptomeningeal amyloidosis
• Known light chain (AL) or secondary amyloidosis (AA), or any other form of systemic amyloidosis
• Acute coronary syndrome, unstable angina, stroke, transient ischemic attack, coronary revascularization, cardiac device implantation, cardiac valve repair, or major surgery within 3 months of Screening
• Uncontrolled clinically significant cardiac arrhythmia, per Investigator's assessment
• LVEF < 30% on echocardiography
• Renal failure requiring dialysis or an eGFR < 20 mL/min/1.73 m2 at Screening
• Polyneuropathy with PND score IV

Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.