Repatha (Evolocumab) for the Treatment of Heterozygous and Homozygous Familial Hypercholesterolemia, United States of America


Repatha (evolocumab) is a new cholesterol lowering injection approved by the FDA in August 2015.

Repatha (evolocumab) is a new 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 hypercholesterolemia (HoFH) in August 2015. It is the second PCSK9 inhibitor approved by the FDA.

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

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

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

Familial hypercholesterolemia

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

Familial hypercholesterolemia is a genetic disorder that causes high levels of LDL cholesterol in the blood. It begins at an early stage and leads to cardiovascular diseases such as heart attacks and strokes. According to the Centers for Disease Control and Prevention, 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 hypercholesterolemia (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.

Clinical trials on Repatha



Liptruzet (ezetimibe and atorvastatin) is a combination drug indicated to reduce elevated low-density lipoprotein (LDL) cholesterol in patients suffering from hyperlipidaemia disorder.


The safety and efficacy of Repatha was evaluated in a 52-week, placebo controlled clinical study and eight 12-week, placebocontrolled clinical trials conducted on subjects with primary hyperlipidemia, including HeFH and HoFH.

Study 1, a multi-centre, double-blind, randomised, controlled study, was conducted on 296 patients with primary hyperlipidemia 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 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 other arm that received 420mg witnessed a -63% change.

Study 2, conducted for 52 weeks, also a multi-centre, double-blind, randomised, placebo-controlled study, enrolled 139 patients with atherosclerotic CVD, who regularly take atorvastatin 80mg. After stabilisation, subjects were randomised to Repatha 420mg or aplacebo. The results demonstrated that the percentage change in the LDL from baseline between the two treatment arms was -54%.

Study 3, 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 4 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%.

Most common adverse reactions observed were injection site reactions, nasopharyngitis, upper respiratory tract infection, back pain and flu.