Repatha

For the treatment of Heterozygous Familial Hypercholesterolemia (HeFH) in patients 18 years of age or older who meet the following criteria:

- Definite or probable diagnosis of HeFH using the Simon Broome or Dutch Lipid Network criteria or genetic testing;

AND

- Unable to reach Low Density Lipoprotein Cholesterol (LDL-C) target (i.e., LDL-C less than 2.0 mmol/L for secondary prevention) or at least a 50% reduction in LDL-C from untreated baseline despite:

A. Confirmed adherence to high dose statin (e.g., atorvastatin 80mg or rosuvastatin 40mg) in combination with ezetimibe for at least a total of 3 months;

OR

B. Confirmed adherence to ezetimibe for at least a total of 3 months and inability to tolerate high dose statin defined as:

(i). Inability to tolerate at least 2 statins with at least one started at the lowest starting dose; AND

(ii). For each statin (two statins in total), dose reduction is attempted for intolerable symptom (myopathy) or biomarker abnormality (creatine kinase (CK) greater than 5 times the upper limit of normal) resolution rather than discontinuation of statin altogether; AND

(iii). For each statin (two statins in total), intolerable symptoms (myopathy) or abnormal biomarker (creatine kinase (CK) greater than 5 times the upper limit of normal) changes are reversible upon statin discontinuation but reproducible by re-challenge of statins where clinically appropriate; AND

(iv). One of the following:

I) Other known determinants of intolerable symptoms or abnormal biomarkers have been ruled out; OR

II) Patient developed confirmed and documented rhabdomyolysis; OR

III) Patient is statin contraindicated i.e., active liver disease, unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal

Treatment with Repatha should be discontinued if the patient does not meet all of the following:

1. Patient is adherent to therapy.

2. Patient has achieved a reduction in LDL-C of at least 40% from baseline (4-8 weeks after initiation of Repatha).

3. Patient continues to have a significant reduction in LDL-C (with continuation of Repatha) of at least 40% from baseline since initiation of PCSK9 inhibitor. LDL-C should be checked periodically with continued treatment with PCSK9 inhibitors (e.g., every 6 months).

Note: Patients prescribed Repatha 140mg every two weeks are limited to 26 prefilled syringes (PFS) per year.

To reduce elevated low-density lipoprotein cholesterol (LDL-C) in adult patients with atherosclerotic cardiovascular disease (ASCVD) when all of the following criteria apply:

1. Patient is aged 18 years or older; AND

2. Patient has experienced a recent acute coronary syndrome (ACS) event, defined as those who have been hospitalized for a heart attack or unstable angina in the past 52 weeks; AND

3. Patient is unable to meet cholesterol targets, defined as having an LDL-C level 1.8mmol/L or greater, OR a non-HDL-C level 2.6mmol/L or greater, OR an Apo-B level 0.7g/L or greater, despite taking maximally tolerated dose of statins*; AND

*Maximally tolerated dose of statins includes one moderate-to-high intensity statin (i.e., at least atorvastatin 20mg daily or equivalent) for at least 4 weeks before treatment OR documented intolerance to at least 2 statins OR contraindication to statin therapy.

4. Patient has received an adequate trial (i.e., at least 4 weeks) of ezetimibe** if only modest reductions in cholesterol targets are required (i.e., those with an LDL-C level of 1.8mmol/L to less than or equal to 2.2mmol/L, OR a non-HDL-C level of 2.6mmol/L to less than or equal to 2.9mmol/L, OR an Apo-B level of 0.7g/L to less than or equal to 0.8g/L) despite taking a maximally tolerated statin dose; AND

**For clarity, an adequate trial of ezetimibe is not required for patients with an LDL-C level greater than 2.2mmol/L, a non-HDL-C level greater than 2.9mmol/L, or an Apo-B level greater than 0.8g/L, despite taking a maximally tolerated statin dose.

5. Prescribed by a healthcare practitioner with expertise managing patients in the post-ACS setting; AND

6. Is not being used in combination with other proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Treatment with Repatha should be discontinued if the patient does not meet all of the following:

1. Patient is adherent to therapy.

2. Patient has achieved a reduction in cholesterol parameters (i.e., LDL-C, and/or non-HDL-C and/or Apo-B) from baseline deemed clinically appropriate by the treating prescriber.

Approved dose: 140mg every 2 weeks. Patients prescribed Repatha 140mg every two weeks are limited to 26 prefilled syringes (PFS) per year.