Novel LDLR-independent therapies, such as lomitapide and evinacumab, reduce LDLC by approximately 50% irrespective of residual LDLR function in patients with homozygous familial hypercholesterolemia.
Do novel pharmacological therapies reduce LDLC in patients with homozygous familial hypercholesterolemia?
Novel LDLR-independent therapies provide significant LDLC reductions in HoFH patients regardless of residual LDLR function, reducing the need for apheresis or transplantation.
PURPOSE OF REVIEW: Homozygous familial hypercholesterolaemia (HoFH) is characterized by marked elevation of low-density lipoprotein cholesterol (LDLC) and premature atherosclerotic cardiovascular disease. This is a review of novel pharmacological therapies to lower LDLC in patients with HoFH. RECENT FINDINGS: Novel therapies can be broadly divided by whether their efficacy is dependent or independent of residual low-density lipoprotein receptor (LDLR) function. Novel LDLR dependent therapies that reduce proprotein subtilisin kexin type 9 levels include monoclonal antibodies (alirocumab and evolocumab) and a small inhibitory RNA (inclisiran). LDLC reductions are highly variable and depend on residual LDLR function. Microsomal triglyceride inhibitors (lomitapide) and therapies that reduce angiopoietin like factor 3 (evinacumab and zodasiran) both reduce LDLC by approximately 50%, irrespective of residual LDLR function. Most patients with HoFH require multiple therapies to achieve LDLC targets. Better LDLC control with LDLR independent therapies is likely to improve the outlook for patients with HoFH while at the same time reducing the need for other therapies such as apheresis or hepatic transplantation.
Blom et al. (Fri,) conducted a review in Homozygous Familial Hypercholesterolemia (HoFH). Novel pharmacological therapies (e.g., lomitapide, evinacumab, PCSK9 inhibitors) was evaluated on Reduction in low-density lipoprotein cholesterol (LDLC). Novel LDLR-independent therapies, such as lomitapide and evinacumab, reduce LDLC by approximately 50% irrespective of residual LDLR function in patients with homozygous familial hypercholesterolemia.