MAFEvolocumab (Repatha) Injection In Prefilled Autoinjector 140 mg/mL
1) Treatment of patients with non-familial hypercholesterolemia or mixed dyslipidaemia, with atherosclerotic cardiovascular disease and additional risk factors and LDL-c level above 1.8 mmol/L despite maximal tolerated lipid-lowering therapy for at least 12 weeks. Subsidy only applies when evolocumab is dosed at 140 mg every 2 weeks.
2) Treatment of patients with heterozygous familial hypercholesterolemia, with atherosclerotic cardiovascular disease and LDL-c level above 1.8 mmol/L despite maximal tolerated lipid-lowering therapy for at least 12 weeks. Subsidy only applies when evolocumab is dosed at 140 mg every 2 weeks.
3) Treatment of patients with heterozygous familial hypercholesterolemia, without atherosclerotic cardiovascular disease, and LDL-c level above 2.6 mmol/L despite maximal tolerated lipid-lowering therapy for at least 12 weeks. Subsidy only applies when evolocumab is dosed at 140 mg every 2 weeks.
4) Treatment of patients with homozygous familial hypercholesterolemia with LDL-c level above 1.8 mmol/L despite maximal tolerated statin-lowering therapy for at least 12 weeks.
Key definitions:
Atherosclerotic cardiovascular disease is defined as
• the presence of symptomatic coronary artery disease (prior myocardial infarction, prior revascularisation procedure, angina associated with demonstrated significant coronary artery disease [i.e. 50% or greater stenosis in 1 or more coronary arteries on imaging]), or positive functional testing (e.g. myocardial perfusion scanning or stress echocardiography); or
• the presence of symptomatic cerebrovascular disease (prior ischaemic stroke, prior revascularisation procedure, or transient ischaemic attack associated with 50% or greater stenosis in 1 or more cerebral arteries on imaging; or
• the presence of symptomatic peripheral arterial disease (prior acute ischaemic event due to atherosclerosis, prior revascularisation procedure, or symptoms of ischaemia with evidence of significant peripheral artery disease [i.e. 50% or greater stenosis in 1 or more peripheral arteries on imaging]).
Additional risk factors include any of the following:
• atherosclerotic disease in two or more vascular territories (coronary, cerebrovascular or peripheral vascular territories); or
• severe multi-vessel coronary heart disease defined as at least 50% stenosis in at least two large vessels; or
• at least two major cardiovascular events (i.e. myocardial infarction, unstable angina, stroke or unplanned revascularisation) in the previous 5 years; or
• diabetes mellitus with microalbuminuria; or
• diabetes mellitus and be aged 60 years or more; or
• Thrombolysis in Myocardial Infarction (TIMI) risk score for secondary prevention of 4 or higher.
For homozygous familial hypercholesterolemia, the condition must have been confirmed by genetic testing.
For heterozygous familial hypercholesterolemia, the condition must have been confirmed by a Dutch Lipid Clinic Network Score of at least 6.
Maximal tolerated lipid-lowering therapy refers to:
• treatment with maximum recommended dose of atorvastatin (40-80mg daily) or rosuvastatin (20-40mg daily) or the maximum tolerated dose of atorvastatin or rosuvastatin, in combination with ezetimibe; or
• patient developed clinically important product-related adverse events^ necessitating withdrawal of statin treatment to trials of each of atorvastatin and rosuvastatin; or
• patient is contraindicated to a statin as defined in the HSA-approved Product Information.
Maximal tolerated statin-lowering therapy refers to:
• treatment with maximum recommended dose of atorvastatin (40-80 mg daily) or rosuvastatin (20-40 mg daily) or the maximum tolerated dose of atorvastatin or rosuvastatin; or
• patient developed clinically important product-related adverse events^ necessitating withdrawal of statin treatment to trials of each of atorvastatin and rosuvastatin; or
• patient is contraindicated to a statin as defined in the HSA-approved Product Information.
^A clinically important product-related adverse event is defined as follows:
• severe myalgia (muscle symptoms without creatine kinase elevation) which is proven to be temporally associated with statin treatment; or
• myositis (clinically important creatine kinase elevation, with or without muscle symptoms) demonstrated by results twice the upper limit of normal on a single reading or a rising pattern on consecutive measurements and which is unexplained by other causes; or
• unexplained, persistent elevations of serum transaminases (greater than 3 times the upper limit of normal) during treatment with a statin.