Lipid-efficacy RCT · N Engl J Med 2020
Evinacumab refractory HC trial
Evinacumab in Patients with Refractory Hypercholesterolemia.
The bottom line
In patients with refractory hypercholesterolemia despite maximal lipid-lowering therapy, evinacumab substantially and significantly lowered LDL cholesterol compared with placebo, with serious adverse events occurring at variable rates across dose groups.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Subcutaneous evinacumab (450 mg weekly, 300 mg weekly, or 300 mg every 2 weeks) or intravenous evinacumab (15 mg/kg every 4 weeks or 5 mg/kg every 4 weeks)
- Compared with
- Placebo (subcutaneous or intravenous)
- People
- 272
- Who took part
- Patients with or without heterozygous familial hypercholesterolemia who had refractory hypercholesterolemia, with a screening LDL cholesterol level of 70 mg per deciliter or higher with atherosclerosis or of 100 mg per deciliter or higher without atherosclerosis
- Design
- double-blind, placebo-controlled, phase 2 trial
- Follow-up
- 16 weeks
- Main question
- Percent change from baseline in LDL cholesterol level at week 16 with evinacumab as compared with placebo
Main result
At week 16, the differences in the least-squares mean change from baseline in the LDL cholesterol level between the groups assigned to receive subcutaneous evinacumab at a dose of 450 mg weekly, 300 mg weekly, and 300 mg every 2 weeks and the placebo group were -56.0, -52.9, and -38.5 percentage points, respectively (P<0.001 for all comparisons). The differences between the groups assigned to receive intravenous evinacumab at a dose of 15 mg per kilogram and 5 mg per kilogram and the placebo group were -50.5 percentage points (P<0.001) and -24.2 percentage points, respectively.
Effect on LDL cholesterol
Reduced LDL cholesterol by more than 50% at the maximum dose; differences vs placebo ranged from -24.2 to -56.0 percentage points across dose groups
Safety
The incidence of serious adverse events during the treatment period ranged from 3 to 16% across trial groups.
In the trial's own words
“At week 16, the differences in the least-squares mean change from baseline in the LDL cholesterol level between the groups assigned to receive subcutaneous evinacumab at a dose of 450 mg weekly, 300 mg weekly, and 300 mg every 2 weeks and the placebo group were -56.0, -52.9, and -38.5 percentage points, respectively (P<0.001 for all comparisons).”
Quoted from the abstract of N Engl J Med 2020, checked word for word against PubMed. PubMed 33196153 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Evinacumab (Evkeeza)
Common questions
What did the Evinacumab refractory HC trial find?
In patients with refractory hypercholesterolemia despite maximal lipid-lowering therapy, evinacumab substantially and significantly lowered LDL cholesterol compared with placebo, with serious adverse events occurring at variable rates across dose groups.
Who was in Evinacumab refractory HC?
272 people. Patients with or without heterozygous familial hypercholesterolemia who had refractory hypercholesterolemia, with a screening LDL cholesterol level of 70 mg per deciliter or higher with atherosclerosis or of 100 mg per deciliter or higher without atherosclerosis.
What was Evinacumab refractory HC's main result?
At week 16, the differences in the least-squares mean change from baseline in the LDL cholesterol level between the groups assigned to receive subcutaneous evinacumab at a dose of 450 mg weekly, 300 mg weekly, and 300 mg every 2 weeks and the placebo group were -56.0, -52.9, and -38.5 percentage points, respectively (P<0.001 for all comparisons). The differences between the groups assigned to receive intravenous evinacumab at a dose of 15 mg per kilogram and 5 mg per kilogram and the placebo group were -50.5 percentage points (P<0.001) and -24.2 percentage points, respectively.
How much did LDL cholesterol change in Evinacumab refractory HC?
Reduced LDL cholesterol by more than 50% at the maximum dose; differences vs placebo ranged from -24.2 to -56.0 percentage points across dose groups
Related trials
- ELIPSE HoFH (2020)In patients with homozygous familial hypercholesterolemia already on maximal lipid-lowering therapy, adding evinacumab markedly lowered LDL cholesterol compared with placebo, with similar adverse event rates.
- APPROACH (2019)In patients with familial chylomicronemia syndrome, volanesorsen substantially lowered triglyceride and apolipoprotein C-III levels compared with placebo but caused frequent injection-site reactions and thrombocytopenia.
- ARCHES-2 (2024)In adults with mixed hyperlipidemia, zodasiran (an RNAi therapy against ANGPTL3) produced significant, dose-dependent reductions in triglycerides and improvements in non-HDL-C, ApoB, and LDL-C compared with placebo, with a signal of transient HbA1c elevation in diabetic patients at the highest dose.
- Balance (2024)In patients with familial chylomicronemia syndrome, olezarsen 80 mg significantly lowered triglycerides and markedly reduced acute pancreatitis episodes compared with placebo, with the 50-mg dose not reaching significance for the triglyceride endpoint.
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