This year at the American Diabetes Association (ADA) Scientific Sessions, new Phase III data were presented evaluating the safety and efficacy of enlicitide, a late-stage investigational oral Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitor. The analysis demonstrated significant reductions in Low-Density Lipoprotein Cholesterol (LDL-C) among participants with and without diabetes mellitus, with no increased risk of worsening glycemia or new-onset diabetes. Together, these findings suggest that enlicitide may offer an effective oral treatment option for dyslipidemia without adversely affecting glycemic control.
Dyslipidemia is a metabolic disorder characterised by abnormal blood lipid levels, including cholesterol and triglycerides, and is a major risk factor for cardiovascular disease. PCSK9 inhibitors are an established class of lipid-lowering therapies used to treat dyslipidemia by reducing LDL-C levels. Currently approved PCSK9 inhibitors are administrated through subcutaneous injections, which could present a barrier to treatment initiation and long-term adherence.
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The findings were derived from an integrated analysis from the Phase III CORALreef Lipids and CORALreef HeFH studies. At Week 24, LDL-C was reduced by 65% in participants with diabetes and 61% in those without. Similar rates of new-onset or worsening diabetes were observed in both enlicitide and placebo arms, with no meaningful changes in HbA1c overtime. These results are clinically meaningful and highlight the potential of oral PCSK9 inhibition to achieve substantial LDL-C reductions regardless of diabetes status, while maintaining glycemic stability. The LDL-C reductions observed with enlicitide appear to approach those seen with established PCSK9 inhibitors. Future head-to-head studies may help clarify how oral and injectable PCSK9 inhibition compare in terms of efficacy, safety and patient acceptability.
From a commercial perspective, enlicitide, as an oral therapy with LDL-C reductions comparable to injectable PCSK9 inhibitors, may address an important unmet need among patients who are unwilling or unable to use injectable therapies. Rather than replacing existing PCSK9 inhibitors, enlicitide may expand the overall use of PCSK9 inhibition by reaching patients who otherwise would unlikely consider injectable therapies. Its oral formulation may also facilitate easier incorporation into existing lipid-lowering treatment pathways, including combination treatment strategies.
Overall, these results suggest that enlicitide has the potential to offer substantial LDL-C lowering through a convenient oral formulation, representing a promising addition to the dyslipidemia treatment landscape.
