In studies, evolocumab reduced LDL-C by up to 75% in patients already taking statins.
The antibody binds to the PCSK9 enzyme (proprotein convertase subtilisin/kexin type 9), preventing PCSK9-mediated degradation of LDL receptors on the liver cell surface and thus increasing metabolism of LDL-C.
"It is over a decade since the last new drug class for cholesterol-lowering therapy was introduced in the UK," said Dr Dermot Neely, lead consultant for the lipid and metabolic outpatient clinic at the Royal Victoria Infirmary in Newcastle.
"We now have a new treatment option which may be considered in patients who are resistant to statins or unable to take them. In particular, our patients with severe forms of FH frequently have persistently raised cholesterol levels and remain at serious risk of having a heart attack or stroke, despite a healthy diet, healthy lifestyle and currently available lipid-lowering treatments in maximum combinations."
Supplied in a prefilled syringe or SureClick pen, Repatha is given by subcutaneous injection monthly or fortnightly and is intended for patients to self-administer following appropriate training.
Repatha is indicated in adults with primary hypercholesterolaemia (heterozygous familial or non-familial) or mixed dyslipidaemia, as an adjunct to diet:
- in combination with a statin with or without other lipid-lowering therapies in patients unable to reach LDL-C goals with a statin alone, or
- alone or in combination with other lipid-lowering therapies in patients who cannot take a statin.
Repatha is also indicated in combination with other lipid-lowering therapies in adults and adolescents from 12 years with homozygous familial hypercholesterolaemia.
The PROFICIO clinical trial programme is evaluating evolocumab in 22 clinical trials, with a combined planned enrollment of approximately 35,000 patients. The primary endpoint for the majority of the pivotal lipid-lowering studies was the percentage change from baseline in LDL-C at week 12 and the mean percentage change from baseline in LDL-C at weeks 10 and 12.
In the studies completed so far, evolocumab produced significant reductions in LDL-C ranging from 55% to 75% in a variety of settings:
- versus ezetimibe in patients with hypercholesterolaemia who cannot tolerate statins (GAUSS-2)
- versus ezetimibe or placebo as a standalone treatment in patients with hypercholesterolaemia (MENDEL-2)
- versus placebo when added to other lipid-lowering therapies in patients with heterozygous familial hypercholesterolaemia (RUTHERFORD-2)
- versus placebo when added to statins in patients with primary hypercholesterolaemia or mixed dyslipidaemia (LAPLACE-2)
- versus placebo when added to other lipid-lowering therapies in patients with homozygous familial hypercholesterolaemia (TESLA).
Five studies will provide long-term safety and efficacy data. These include OSLER and OSLER-2, which showed sustained LDL-C reductions after 1 year when evolocumab was added to standard care in patients with hypercholesterolaemia. Sustained LDL-C responses were also seen in the DESCARTES study versus placebo at 52 weeks when evolocumab was given as monotherapy or added to atorvastatin in patients with hyperlipidaemia.
TAUSSIG is an ongoing 5-year study assessing the long-term effects of evolocumab in patients with severe familial (including homozygous) hypercholesterolaemia. Interim results showed a sustained 48% reduction in LDL-C at 36 weeks.
The most commonly reported adverse reactions of evolocumab were nasopharyngitis (4.8%), upper respiratory tract infection (3.2%), back pain (3.1%), arthralgia (2.2%), influenza (2.3%) and nausea (2.1%).