Table 2: Summary of the characteristics of patisiran.

Characteristics	Notes
Mechanism of action	Small interfering ribonucleic acid that causes degradation of the TTR mRNA
Dose	80 min intravenous infusion every 3 weeks. Dosage is based on bodyweight: <100 kg=0.3 mg/kg; >100 kg=30 mg
Premedication	Dexamethasone, paracetamol, ranitidine and antihistamine
Pharmacokinetics	Systemic exposure increases in a linear and dose-proportional manner Greater than 95% of circulating patisiran is associated with the lipid complex A steady state is reached by 24 weeks Patisiran is metabolized into nucleotides of various lengths Half-life is 3 ± 2 days Less than 1% is excreted unchanged in the urine Mild-to-moderate renal dysfunction and mild hepatic impairment do not affect the pharmacokinetics
Pharmacodynamics	Mean serum TTR reduction of approximately 80% within 10-14 days after single dose Maximum reduction of serum TTR after a single dose of 88% Mean reduction of serum TTR at 12 months of 87% Similar reductions occur regardless of mutation, age, sex or race Mean reductions of serum retinol binding protein of 45% and serum vitamin A of 62% occur at 18 months
Neurological trial outcomes	APOLLO: Reduced mNlS+7 Reduced Norfolk QOL Reduced COMPASS-31 Increased gait speed
Cardiology trial outcomes	APOLLO prespecified cardiac population: Reduced serum NT-proBNP Increased gait speed Reduced left ventricular wall thickness Increased left ventricular end diastolic volume APOLLO-B: Increased 6-min walk test Increased KCCQ-OS Improved longitudinal strain
Potential adverse events	Infusion-related reactions including but not limited to back pain, nausea, abdominal pain, dyspnoea, chills, flushing and headache Upper respiratory tract infections Vitamin A deficiency Peripheral oedema

KCCQ-OS = Kansas City Cardiomyopathy Questionnaire Overall Summary Score; mNIS+7 = modified Neuropathy Impairment Score +7 neurophysiologic tests; NT proBNP = N-terminal pro B-type natriuretic peptide; QOL = quality of life; TTR = transthyretin.