- Evinacumab reduced low-density lipoprotein-cholesterol (LDL-C) levels by almost half in patients with homozygous familial hypercholesterolaemia (HoFH), regardless of their LDL receptor function.
Why this matters
- Even when treated with standard lipid-lowering therapies, including statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, many patients with HoFH continue to have elevated LDL-C levels.
- In this phase 3 trial, 65 patients with HoFH (age, ≥12 years) were randomly assigned to receive evinacumab intravenously every 4 weeks (n=43) or placebo (n=22).
- Primary outcome: between-group percentage change in LDL-C after 24 weeks.
- Funding: Regeneron Pharmaceuticals.
- Baseline LDL-C levels averaged about 250 mg/dL; about 30% had null/null mutations, >90% were on statin therapy and about three-quarters were on PCSK9 inhibitor.
- At week 24, average LDL-C levels reduced by 47% (an average drop of 135 mg/dL) in patients receiving evinacumab vs an average increase of 2% in those receiving placebo, resulting in an average relative reduction of 49% for evinacumab.
- LDL-C reduced by at least 50% in 56% of the evinacumab-treated patients and in 5% of control patients.
- Similar levels of LDL-C lowering were observed in patients with a minimal residual level of LDL receptor activity, patients known as having “null/null” mutations.
- Evinacumab was also effective in lowering baseline triglyceride levels by half.
- Evinacumab was well tolerated with no serious adverse events.
- Small sample size.
- Short study duration.
Dr Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis, said: “One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance.”