Did the phase 3 trial of oral PCSK9 inhibitor enlicitide show results?

Enlicitide decanoate is an oral PCSK9 inhibitor being studied for lowering LDL cholesterol in people with hypercholesterolemia. Several phase 3 trials have recently reported results, showing that enlicitide significantly reduces LDL-C and is more effective than other oral nonstatin therapies like ezetimibe and bempedoic acid.

What the research says

A phase 3 trial in patients with heterozygous familial hypercholesterolemia (HeFH) found that enlicitide 20 mg daily reduced LDL-C by a mean of 60.2% from baseline at week 24, compared to 5.9% with placebo ⁷. Another large placebo-controlled trial in patients with atherosclerotic cardiovascular disease or at high risk reported a mean LDL-C reduction of 60.0% at week 24 with enlicitide versus 1.9% with placebo ⁸. A third phase 3 trial directly compared enlicitide to other oral nonstatin therapies: enlicitide reduced LDL-C by 60.1% at day 56, while ezetimibe reduced it by 21.2%, bempedoic acid by 21.5%, and the combination of ezetimibe plus bempedoic acid by 36.2% ⁹. Enlicitide was also superior to these comparators in reducing apolipoprotein B and non-HDL cholesterol ⁹. Safety data from these trials indicate that enlicitide was generally well tolerated, with adverse event rates similar to placebo and active comparators ⁷⁸⁹. A separate phase 3 trial listed on a registry (NCT06306638) was completed but had not posted results at the time of the registry entry ⁶.

What to ask your doctor

• Could enlicitide be an option for me if I am not reaching my LDL-C goals with current medications?
• How does enlicitide compare to injectable PCSK9 inhibitors in terms of effectiveness and convenience?
• What are the potential side effects or drug interactions I should know about with enlicitide?
• Is enlicitide appropriate for my specific type of hypercholesterolemia (e.g., familial or not)?
• When might enlicitide become available, and would my insurance cover it?