FDA Approves Merck's Lipfendra, the First Oral PCSK9 Inhibitor Approved in the US
The once-daily enlicitide tablet cut LDL cholesterol by a placebo-adjusted 56% and 59% in two Phase 3 trials; whether it reduces heart attacks and deaths is still being studied.
The FDA approved this drug or biologic for a specific use.
Key points
- The FDA approved Merck's Lipfendra (enlicitide) 20 mg tablets on July 16 to lower LDL cholesterol in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia, alongside diet and exercise.
- Approval rested on the Phase 3 CORALreef Lipids and CORALreef HeFH trials, in which the drug reduced LDL cholesterol by 56% and 59% versus placebo at week 24, Merck said.
- Merck is launching the pill at a list price of $315 per month, BioSpace reported; a cardiovascular outcomes trial of more than 14,500 participants is ongoing.
The US Food and Drug Administration has approved Merck's Lipfendra (enlicitide) tablets 20 mg as an add-on to diet and exercise to lower low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH), the company announced on July 16. Merck said Lipfendra is the first FDA-approved oral PCSK9 inhibitor shown to lower LDL-C.
PCSK9 inhibitors already on the US market, such as Repatha and Praluent, are given by injection. Lipfendra is a once-daily pill built on a macrocyclic peptide that binds PCSK9 and blocks its interaction with LDL receptors, according to Merck.
The trials behind the approval
The approval is based on two Phase 3 trials from Merck's CORALreef program. In CORALreef Lipids, which randomised 2,904 patients with hypercholesterolemia and a history of, or increased risk for, a major atherosclerotic cardiovascular event, Lipfendra reduced LDL-C by 56% compared with placebo at week 24. Patients were already on stable statin therapy unless they were statin-intolerant. In CORALreef HeFH, which enrolled 303 patients with the inherited condition, the reduction was 59% versus placebo at week 24, Merck said. Both trials randomised patients 2:1 to the drug or placebo for 52 weeks.
Merck said the safety profile in CORALreef Lipids was similar to placebo. In CORALreef HeFH, the most common adverse reactions that occurred more often than with placebo were diarrhoea (7% versus 2%) and dizziness (9% versus 4%). In both trials, similar proportions of patients on the drug and on placebo stopped treatment because of an adverse reaction.
"In two Phase 3 trials, LIPFENDRA led to impressive reductions in LDL-C," said Ann Marie Navar, a lead author of the CORALreef Lipids study and associate professor of medicine at UT Southwestern Medical Center, in Merck's announcement.
The release states that it is not yet known whether Lipfendra reduces cardiovascular illness and death. The CORALreef Outcomes trial, which has completed enrollment of more than 14,500 participants, is studying that question.
Review, price and competition
Lipfendra was approved under the FDA's Commissioner's National Priority Voucher program, which is designed to speed reviews of medicines aligned with certain US government priorities, BioSpace reported. BioSpace counted it as the ninth approval under the program.
Merck is launching the drug at $315 per month, which BioSpace described as a discount to injectable PCSK9 inhibitors that range from $500 to $600 a month. RBC Capital Markets estimated peak annual sales of about $5 billion by 2034, according to BioSpace. AstraZeneca is developing its own oral PCSK9 candidate, AZD0780, the outlet reported.