Key result
ANGPTL3 inhibitors, including evinacumab and ARO-ANG3, effectively lower LDL-C by up to 50% in patients with homozygous familial hypercholesterolemia.
Why the study?
Most patients with severe hypercholesterolemia, particularly homozygous familial hypercholesterolemia, cannot achieve target LDL-C levels with available standard lipid-lowering therapy.
Does ANGPTL3 inhibition reduce LDL-C in patients with severe hypercholesterolemia, particularly HoFH?
Does ANGPTL3 inhibition reduce LDL-C in patients with severe hypercholesterolemia, particularly HoFH?
ANGPTL3 inhibition represents a promising novel therapeutic strategy to achieve target LDL-C levels in patients with severe hypercholesterolemia, particularly HoFH, potentially reducing the need for lipoprotein apheresis.
May support ANGPTL3 inhibition for LDL-C lowering in HoFH; leaves open need for randomized outcome trials before practice change.
PURPOSE FOR REVIEW: Despite the therapeutic advances for patients with severe hypercholesterolemia, particularly those with homozygous familial hypercholesterolemia (HoFH), most patients are unable to achieve target low-density lipoprotein cholesterol (LDL-C) levels with the current available standard lipid-lowering therapy (LLT). We review the role of angiopoietin-like 3 (ANGPTL3) inhibition as an additional therapeutic option for severe hypercholesterolemia, particularly HoFH. RECENT FINDINGS: Evinacumab is a monoclonal antibody against ANGPTL3, and reduces LDL-C independent of LDL-receptor activity. ANGPTL3 inhibitors are effective in lowering LDL-C in patients with FH, with a 50% reduction in LDL-C in those with HoFH. Longer-term efficacy and safety have been demonstrated with reductions in LDL-C maintained following 48 weeks of therapy. Gene silencing strategies directed against ANGPTL3 include antisense oligonucleotide and small-interfering ribonucleic acid (siRNA). ARO-ANG3 is a siRNA directed against ANGPTL3 messenger ribonucleic acid and is associated with up to a 42% reduction in LDL-C. SUMMARY: With the promise of these emerging novel therapeutics directed against ANGPTL3 on the horizon, achieving acceptable target LDL-C levels in HoFH without the need for lipoprotein apheresis may finally be a realistic goal and we can anticipate a decrease in cardiovascular morbidity and mortality in these difficult to treat patients.
No takes yet. Share an insight, caveat, or question.
Mohamed et al. (2021) conducted a review in Severe hypercholesterolemia, particularly homozygous familial hypercholesterolemia (HoFH). ANGPTL3 inhibitors (evinacumab, ARO-ANG3) was evaluated on LDL-C reduction. ANGPTL3 inhibitors, including evinacumab and ARO-ANG3, effectively lower LDL-C by up to 50% in patients with homozygous familial hypercholesterolemia.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: