Repatha (evolocumab) is indicated for heterozygous familial hypercholesterolaemia (HeFH). Credit: Amgen.
Repatha can be self-administered by patients. Credit: PRNewswire / MultiVu.
The drug is available as a single-use 140mg pre-filled SureClick autoinjector. Credit: PR Newswire / MultiVu.

Repatha (evolocumab) is a cholesterol-lowering injection developed by Amgen that was approved by US Food and Drug Administration (FDA) as an adjunctive treatment for adults with heterozygous familial and homozygous familial hypercholesterolaemia (HoFH) in August 2015. It is the second PCSK9 inhibitor to be approved by the FDA.

Repatha is used as an adjunctive therapy to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolaemia (HeFH), HoFH or clinical atherosclerotic cardiovascular diseases.

These include strokes and heart attacks that have uncontrolled cholesterol levels despite treatment with statins or other cholesterol-controlling medicines and need additional intensive cholesterol-reducing treatment.

Repatha was the first PCSK9 inhibitor to be approved in Europe for the treatment of adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia and HoFH. The European Commission (EC) granted marketing authorisation for the drug in July 2015.

In September 2021, the FDA approved the use of Repatha to reduce low-density lipoprotein cholesterol (LDL-C) in HeFH paediatric patients aged ten years and older. The approval was based on the HAUSER-RCT Phase 3b study.

Familial hypercholesterolaemia details

Familial hypercholesterolaemia is a genetic disorder that causes high levels of LDL-C in the blood. It begins at an early stage and leads to cardiovascular diseases such as heart attacks and strokes. According to the US Centres for Disease Control and Prevention (CDC), heart diseases are one of the leading causes of death in the US, causing 610,000 deaths a year.

An estimated 11 million people in the US suffer from familial hypercholesterolaemia (FH), having uncontrolled levels of LDL despite treatment with statins or other cholesterol reducing medicines.

Repatha’s mechanism of action, dosage and administration

Repatha contains an active ingredient called evolocumab, a human monoclonal antibody that inhibits the PCSK9 (proprotein convertase subtilisin/kexin type) protein, which reduces the liver’s ability to remove LDL from the blood.

Evolocumab inhibits PCSK9 protein and prevents it from binding to the LDL receptor (LDLR), allowing LDLR to recycle back to the liver. By inhibiting the protein, the drug increases the number of LDLRs to clear from the blood, reducing LDL levels.

Repatha is available in the form of a single-use 140mg pre-filled syringe for subcutaneous injection. The recommended dosage is 140mg every two weeks or 420mg once a month.

Repatha contains an active ingredient called evolocumab, a human monoclonal antibody that inhibits the PCSK9 (proprotein convertase subtilisin/kexin type) protein.

Clinical trials on Repatha

Repatha’s safety and efficacy were evaluated in a 52-week, placebo-controlled clinical study and eight 12-week, placebo-controlled clinical trials conducted on subjects with primary hyperlipidaemia, including HeFH and HoFH.

Study One, a multi-centre, double-blind, randomised, controlled study, was conducted on 296 patients with primary hyperlipidaemia with clinical atherosclerotic cardiovascular disease (CVD).

For the initial four-week period, subjects were randomised to a statin regimen followed by random treatment with Repatha 140mg every two weeks or 420mg once a month or a placebo for 12 weeks. Subjects were treated with Repatha in addition to their regular doses of atorvastatin 80mg, rosuvastatin 40mg or simvastatin 40mg.

Results after week 12 showed a significant difference between the percentage change in LDL levels between patients treated with Repatha and a placebo. The change was -71% in the treatment arm that received 140mg of Repatha, whereas the arm that received 420mg witnessed a -63% change.

Study Two, conducted for 52 weeks, was also a multi-centre, double-blind, randomised, placebo-controlled study. The trial enrolled 139 patients with atherosclerotic CVD, who regularly take atorvastatin 80mg. After stabilisation, subjects were randomised to Repatha 420mg or placebo. The results demonstrated that the percentage change in the LDL from baseline between the two treatment arms was -54%.

Study Three, conducted for 12 weeks, enrolled 329 patients with HeFH and on statins with or without other therapies. Subjects were randomised to Repatha 140mg or 420mg or a placebo. The average LDL baseline was 156mg/dL. Results showed that the percentage change from baseline was -61% for patients who received 140mg and -60% for those who received 420mg.

Study Four was conducted for 12 weeks on 49 subjects with HoFH on statins and ezetimibe. The subjects were randomised to Repatha and a placebo. The mean baseline LDL was 349mg/dL. Results demonstrated the percentage change in the LDL from baseline between the two treatment arms was -31%.

Common adverse reactions observed in patients in the trial included injection site reactions, nasopharyngitis, upper respiratory tract infection, back pain, and flu.


In August 2020, Amgen announced positive data from the HAUSER-RCT Phase 3b study to evaluate the safety, efficacy and tolerability of 24 weeks of monthly Repatha subcutaneous injections in paediatric patients.

HAUSER-RCT was a multi-centre, randomised, double-blind, placebo-controlled clinical trial in which patients were administered with 420mg Repatha (n=104) and placebo (n=53). The trial’s primary endpoint was to measure the percentage change in LDL-C from baseline to week 24. When compared with placebo, monthly Repatha treatment reduced LDL-C by a mean of 38% from baseline.


In August 2021, Amgen announced positive data from another Phase III study, HUYGENS, which showed that Repatha significantly improved features of plaque stability in coronary artery disease (CAD) patients by increasing the fibrous cap thickness by 42.7um.

The randomised and double-blind 52-week study demonstrated that treatment with Repatha reduces LDL-C from 140 to 28mg/dL versus reductions from 142 to 87mg/dL with statin optimisation alone.

The most frequent adverse reactions observed during Repatha treatment were myalgia, fatigue, angina pectoris, cough, diarrhoea, and hypertension.