At the KAHN CENTER, we strived to identify, quantify, and then reverse atherosclerosis in coronary arteries and other vascular systems. There is a multi-pronged approach emphasizing lifestyle first but pharmacologic agents are used when needed are and advancing rapidly. One of the classes of medications used is PCSK9 inhibitors, to date, only available by injection.
A new oral agent, enclicitide, has been studied and now released for use. Is this a major breakthrough? A new study indicates the power of this agent, known as Lipfrendra, to lower both cholesterol and Lipoprotein(a).
Enlicitide (MK-0616) is an oral PCSK9 inhibitor for the treatment of hypercholesterolemia.
The authors conducted the first systematic review and meta-analysis evaluating the efficacy and safety of enlicitide across randomized controlled trials enrolling adults with hypercholesterolemia or heterozygous familial hypercholesterolemia (HeFH). The primary outcome was the baseline-to-endpoint percentage change in low-density lipoprotein cholesterol (LDL-C); secondary outcomes included apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein(a) [Lp(a)], and safety.
Four randomized controlled trials involving 3894 participants were included. Enlicitide achieved a substantial reduction in LDL-C of-56%, with sustained efficacy demonstrated in the newly available 52-week Phase 3 CORALreef data.
Significant reductions were also observed in ApoB (MD: -48%), non-HDL-C (-49%), and Lp(a) (-23%).
The pooled incidence of any adverse event was not statistically significant, and treatment discontinuation due to adverse events was uncommon.
Enlicitide demonstrated substantial lipid-lowering efficacy with an acceptable safety profile. The ongoing CORALreef Outcomes trial will determine whether these lipid improvements translate into reductions in major adverse cardiovascular events.
This new agent offers the ease of oral administration as well powerful cholesterol and lipoprotein(a) lowering abilities. It also appears to have a favorable side effect profile compared with the placebo groups studied.
Lipfendra is entering shelves at pharmacies and insurance companies are developing algorithms for indications and approval. The cash buy price is considerable (about $300 a month) but lower than when injectable PCSK9 inhibitors were released.
At the KAHN CENTER, we welcome new modalities of treatment that aid in achieving targets and assisting reversal and prevention of atherosclerosis. This new agent will become part of the approach to risk reduction and healthspan creation.
