From the Guidelines
The recommended treatment for Homozygous Familial Hypercholesterolemia (HoFH) involves an aggressive, multi-faceted approach combining maximum-tolerated statins with additional lipid-lowering therapies, including PCSK9 inhibitors such as Repatha (evolocumab), which has been shown to significantly reduce LDL-C levels and improve cardiovascular outcomes 1.
Key Components of Treatment
- High-intensity statins (atorvastatin 40-80mg or rosuvastatin 20-40mg daily) combined with ezetimibe 10mg daily as first-line therapy
- Additional treatments such as PCSK9 inhibitors (evolocumab 420mg or alirocumab 150mg subcutaneously every 2-4 weeks) for patients who do not achieve guideline-recommended LDL-cholesterol goals despite maximally tolerated statin therapy
- LDL apheresis, a dialysis-like procedure that physically removes LDL particles from blood, is often required every 1-2 weeks for patients with severe HoFH
- Treatment should begin as early as possible after diagnosis, even in childhood, and continue lifelong
Goals of Treatment
- Reduce LDL-C levels by at least 50% from baseline, though ideally to below 100mg/dL (or below 70mg/dL for patients with established cardiovascular disease)
- Improve cardiovascular outcomes, including reducing the risk of major adverse cardiovascular events (MACE) such as myocardial infarction, stroke, and cardiovascular death
Role of Repatha (Evolocumab)
- Evolocumab is a PCSK9 inhibitor that has been shown to significantly reduce LDL-C levels and improve cardiovascular outcomes in patients with HoFH 1
- The recommended dose of evolocumab for patients with HoFH is 420mg subcutaneously every 4 weeks
- Evolocumab can be used in combination with other lipid-lowering therapies, including statins, ezetimibe, and LDL apheresis, to achieve optimal LDL-C reduction and improve cardiovascular outcomes.
From the FDA Drug Label
As an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH), to reduce LDL-C The initial recommended dosage of REPATHA is 420 mg once monthly administered subcutaneously The dosage can be increased to 420 mg every 2 weeks if a clinically meaningful response is not achieved in 12 weeks.
The recommended treatment for patients with Homozygous Familial Hypercholesterolemia (HoFH) to reduce Low-Density Lipoprotein Cholesterol (LDL-C) levels is Evolocumab (REPATHA), with an initial dosage of 420 mg once monthly administered subcutaneously, which can be increased to 420 mg every 2 weeks if a clinically meaningful response is not achieved in 12 weeks 2.
From the Research
Treatment for Homozygous Familial Hypercholesterolemia (HoFH)
The recommended treatment for patients with HoFH to reduce Low-Density Lipoprotein Cholesterol (LDL-C) levels and improve cardiovascular outcomes includes the use of evolocumab (Repatha), a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) 3, 4, 5.
Efficacy of Evolocumab
- Evolocumab has been shown to significantly reduce LDL-C levels in patients with HoFH, with a treatment difference of approximately 30% vs. placebo when added to statins with or without ezetimibe in a 12-week phase III trial 3.
- The efficacy of evolocumab was maintained in the longer term, and it was well tolerated 3.
- Evolocumab also significantly lowered LDL-C levels in patients with heterozygous familial hypercholesterolemia who were receiving statins with or without other lipid-lowering drugs 3, 6.
- In pediatric patients with HoFH, evolocumab was well tolerated, with no new safety signals reported, and showed marked variability in LDL-C reduction 7.
Safety and Tolerability
- The safety and tolerability of evolocumab have been evaluated in several studies, with rates of adverse events, serious adverse events, and adverse events leading to discontinuation similar to those of controls in clinical trials 3, 4, 6, 7.
- Evolocumab was well tolerated in patients with HoFH, with no increase in adverse events observed when used in combination with statins 4.