ConexiantOral PCSK9 Inhibitor Tied to LDL-C Drop

Oral PCSK9 inhibitor enlicitide achieved 58% LDL-C reduction in patients with heterozygous familial hypercholesterolemia, matching injectable monoclonal antibody efficacy without injection burden. Phase 3 trial enrolled 303 adults on maximally tolerated statin therapy across 59 sites in 17 countries.

🔬 CLINICAL CONSIDERATIONS

• Oral delivery eliminates injection barrier that limits PCSK9 monoclonal antibody uptake despite proven cardiovascular benefit and guideline recommendations
• LDL-C reductions sustained through 52 weeks with 96% medication adherence, addressing adherence concerns common with injectable PCSK9 inhibitors
• 67% of patients achieved LDL-C under 55 mg/dL, meeting aggressive secondary prevention targets for highest-risk atherosclerotic cardiovascular disease patients
• Safety profile comparable to placebo across hepatic, renal, metabolic, and cardiovascular parameters—no treatment-related serious adverse events observed

💊 PRACTICE APPLICATIONS

• Consider enlicitide for statin-intolerant patients currently unable to achieve LDL-C goals
• Counsel patients on required 30-minute fasting protocol before taking medication daily
• Reserve prescribing until cardiovascular outcomes trial data available (currently ongoing study)
• Monitor baseline and follow-up lipid panels at standard intervals per guideline recommendations

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