FDA approves Merck's oral PCSK9 inhibitor LIPFENDRA

Merck, known as MSD outside the United States and Canada, said the U.S. Food and Drug Administration cleared LIPFENDRA (enlicitide) 20 mg tablets. The once-daily oral treatment is cleared for adults with hypercholesterolemia, including the heterozygous familial form, to lower low-density lipoprotein cholesterol (LDL-C) as an add-on to diet and exercise. LIPFENDRA is the first oral PCSK9 inhibitor to receive FDA approval. Merck said the drug uses a novel macrocyclic peptide technology to block the interaction of PCSK9 with LDL receptors.

Approval rests on two randomized, double-blind, placebo-controlled Phase 3 studies from the CORALreef program: CORALreef Lipids and CORALreef HeFH. Both trials used the average percent change in LDL-C from baseline to week 24 as the primary endpoint.

In CORALreef Lipids, 1,935 patients received LIPFENDRA and 969 received placebo. At week 24, the placebo-adjusted reduction in LDL-C was 56%, and the mean reduction from baseline among patients taking LIPFENDRA was 57%. After excluding biologically impossible baseline values, the placebo-adjusted reduction was 60%. In CORALreef HeFH, 202 patients were assigned to LIPFENDRA and 101 to placebo; after 24 weeks the placebo-adjusted LDL-C reduction was 59%, and the mean reduction from baseline was 58%.

Secondary endpoints showed reductions in non-HDL-C and apolipoprotein B: 54% and 50%, respectively, in CORALreef Lipids, and 52% and 48% in CORALreef HeFH.

In CORALreef Lipids, the safety profile of LIPFENDRA was similar to placebo. In CORALreef HeFH, diarrhea occurred in 7% of LIPFENDRA patients versus 2% on placebo, and dizziness in 9% versus 4%. Across both trials, the share of patients stopping because of adverse reactions was similar in the LIPFENDRA and placebo arms.

Merck Research Laboratories president Dean Y. Li said the medicine offers a convenient pill option that can significantly lower LDL-C. A cardiovascular outcomes trial now underway is testing whether LIPFENDRA affects cardiovascular morbidity and mortality; according to the source, it is not yet known if the drug can reduce those risks.