FDA approves first oral cholesterol pill for high-risk patients

The Food and Drug Administration approved Merck’s enlicitide, sold as Lipfendra, as the first oral PCSK9 inhibitor in the United States, giving doctors a once-daily pill to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia. The drug is intended as an adjunct to diet and exercise for high-risk patients who have not reached cholesterol goals on existing treatment.

That group includes people who have already had a heart attack or stroke, along with patients carrying inherited lipid disorders that can drive LDL to dangerous levels. Merck’s approval gives clinicians another option between standard statin therapy and the injectable drugs that have defined the newer end of lipid treatment.

The pill works differently from a statin because it inhibits PCSK9, a protein that helps regulate how much LDL cholesterol stays in the bloodstream. PCSK9 inhibitors have previously been available mainly as injectable drugs, which can be effective but are not always easy for patients to start or continue. A once-daily tablet may be simpler to prescribe and simpler to take, especially for patients who have struggled to hit LDL goals on current regimens.

Insurance coverage, out-of-pocket cost and how quickly physicians add the drug to routine care will determine whether the approval changes treatment beyond specialist clinics. For patients and doctors, the appeal is straightforward: an oral option may improve adherence for people who have been reluctant to use injections or who need stronger LDL lowering without adding another shot to a long medication list.

Clinical trial results showed substantial LDL reductions, with the pill lowering cholesterol far below statin-only results. The approval follows earlier non-statin cholesterol drugs, including bempedoic acid in 2020 and inclisiran in 2021, but Lipfendra is the first oral PCSK9 inhibitor to clear the agency.