Instalab ResearchRepatha is a fully human monoclonal antibody that binds to PCSK9, a protein that normally degrades LDL receptors in the liver. By blocking PCSK9, Repatha allows more LDL receptors to recycle, removing LDL-C from circulation. Clinical trials consistently show LDL-C reductions of around 60% compared with placebo or ezetimibe, making it one of the most effective non-statin lipid-lowering agents available.
For adults with primary hyperlipidemia, including those with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH), two dosing regimens are recommended:
Both regimens are delivered subcutaneously, either by autoinjector, prefilled syringe, or automated mini-doser. The MENDEL-2 trial, a phase III randomized controlled trial, showed that both regimens significantly reduced LDL-C compared with placebo or ezetimibe in patients not on background therapy. Reductions averaged over 55% from baseline, with excellent tolerability.
The RUTHERFORD-2 trial, a randomized, double-blind, placebo-controlled study in HeFH patients, confirmed that both 140 mg every two weeks and 420 mg monthly reduced LDL-C by around 60% compared with placebo, validating the flexibility of either dosing schedule.
A meta-analysis of randomized trials compared the two regimens directly and found that 140 mg every two weeks was slightly more effective than 420 mg monthly in patients also taking statins, although both schedules were highly efficacious and well tolerated.
Patients with familial hypercholesterolemia (FH) present unique dosing needs. In heterozygous FH, both standard regimens are highly effective, lowering LDL-C by about 60%. Long-term extension studies such as OSLER-1 and OSLER-2 demonstrated that these reductions were durable over one year and beyond, with continued safety.
In homozygous FH, efficacy depends on whether patients retain some LDL receptor function. The TESLA Part B trial, a randomized, double-blind, placebo-controlled study, showed that evolocumab 420 mg every four weeks reduced LDL-C by about 31% in patients with homozygous FH who retained residual receptor activity. Patients without receptor function derived minimal benefit. This underscores the need for individualized treatment planning in this severe genetic disorder.
In 2021, the FDA approved Repatha for pediatric patients aged 10 years and older with heterozygous FH. This approval was based on randomized controlled data demonstrating that dosing regimens of 140 mg every two weeks or 420 mg monthly produced LDL-C reductions similar to those seen in adults, with a favorable safety profile. This allows earlier intervention in children who face lifelong exposure to high LDL-C and early cardiovascular risk.
LDL-C lowering is important, but cardiovascular outcomes ultimately matter most. The FOURIER trial, a landmark randomized trial, evaluated over 27,000 patients with ASCVD already on statins. Adding evolocumab reduced major cardiovascular events, including myocardial infarction and stroke, by 15%. The benefit was proportional to LDL-C lowering, even at very low cholesterol levels, and the drug was well tolerated.
Extension studies confirmed that these benefits persisted long-term, with no new safety concerns, including no evidence of cognitive impairment despite LDL-C levels dropping below 30 mg/dL in some patients.
Although clinical trial data show equivalent efficacy between the two Repatha dosing regimens, real-world considerations often guide choice. Patients who prefer fewer injections may opt for the monthly dose, while those who prefer steady dosing or who experience better lipid stability may select the biweekly regimen. Both schedules offer flexibility without compromising safety or effectiveness.
If you are looking for ways to lower your cholesterol and are not able to take statins, you may be eligible for a Repatha prescription through an Instalab physician:
