Brand Name: Repatha
Generic Name: evolocumab
Drug Class: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor
Similar Drugs: alirocumab (Praluent)
Manufacturer: Amgen Inc.
FDA Approval Date: August 27, 2015
What is Repatha and its mechanism of action?
Repatha belongs to a brand new class of drugs known as proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors. Repatha is an antibody that targets PCSK9. Antibodies are proteins that attack foreign substances that invade the body by binding to them. Antibodies can also be designed in the lab to target substances that are native to the body as well (such as PCSK9).
PCSK9 is a protein that reduces the number of receptors that remove cholesterol, such as low-density lipoprotein (LDL) cholesterol, from the blood. LDL cholesterol is commonly known as the “bad” cholesterol. When too much LDL cholesterol circulates in the blood it can slowly build up in the inner walls of the arteries. Thick, hard deposits (plaque) can narrow the arteries causing atherosclerosis. In addition, these plaques can detach and cause a heart attack, stroke or other atherosclerotic cardiovascular disease (ASCVD). By blocking PCSK9, Repatha allows more receptors to be available to remove LDL cholesterol from the blood — resulting in decreased LDL levels and lower risk of forming dangerous plaques.
What are the uses for Repatha?
The FDA approved Repatha to be used with diet and statin therapy for the treatment of adults who have one of the following conditions and require an additional reduction in LDL cholesterol:
1. Primary Hyperlipidemia: Heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD)
2. Homozygous Familial Hypercholesterolemia (HoFH)
HeFH is a genetic disorder, which causes partial LDL receptor deficiency. Patients with HeFH only have half the normal number of LDL receptors for clearing LDL cholesterol. LDL is hard to remove from the body, resulting in abnormally elevated LDL cholesterol levels. HeFH approximately affects 1 in 500 people in the United States and causes a 2-fold increase in LDL levels (i.e., 190 – 350 mg/dL).
HoFH is a genetic disorder that causes a complete deficiency of LDL receptors. It is a rare disease, which affects about 1 in 1,000,000 in the United States. Unlike HeFH patients, patients with HoFH have very little or no LDL receptor expression, resulting in a 4-fold increase in LDL levels (i.e., 400-1000 mg/dL).
How effective is Repatha for reducing cholesterol?
Patients (n=296) ASCVD who were receiving maximally tolerated doses of statins (atorvastatin 80 mg, rosuvastatin 40mg, or simvastatin 40 mg) were given Repatha 140 mg every 2 weeks, or 420 mg once monthly, or placebo as add-on therapy for 12 weeks. The mean difference between Repatha and placebo in LDL level reduction measured at week 12 was -71% for patients who received 140 mg every 2 weeks and – 63% for patients who received 420 mg once monthly.
In another 52-week trial, 139 patients with ASCVD received atorvastatin 80 mg daily with or without ezetimibe 10 mg daily plus Repatha 420 mg once monthly or placebo. After 52 weeks of treatment, the average difference between Repatha and placebo in LDL level reduction was – 54%.
In a 12-week trial, 329 patients with HeFH received statins with or without other lipid-lowering therapies and Repatha 140 mg every 2 weeks or 420 mg once monthly, or placebo. 38% of these patients had HeFH and ASCVD. The average difference between Repatha and placebo in LDL level reduction measured at week 12 was -61% for patients who received 140 mg every 2 weeks and – 60% for patients who received 420 mg once monthly.
To study the efficacy of Repatha in patients with HoFH, a 12-week trial in 49 patients with HoFH who were on other lipid-lowering therapies was conducted. 33 patients were given 420 mg Repatha once monthly and 16 patients received placebo. In this trial, the average difference between Repatha and placebo in LDL level reduction was -31%.