The FDA approved Merck's Lipfendra (enlicitide) as the first oral PCSK9 inhibitor for lowering LDL cholesterol in adults with hypercholesterolemia. The once-daily 20 mg pill reduced LDL by 56% in a Phase 3 trial of 2,904 patients. The approval positions Merck to compete with injectable rivals Repatha and Praluent.
The FDA approved Merck's Lipfendra (enlicitide) 20 mg as the first oral PCSK9 inhibitor to lower LDL cholesterol in adults with hypercholesterolemia, including those with heterozygous familial hypercholesterolemia.
"High LDL-C is a major risk factor for atherosclerotic cardiovascular disease, which is the leading cause of death globally," Ann Marie Navar, MD, PhD, associate professor of medicine in the Division of Cardiology at UT Southwestern Medical Center and lead author of the CORALreef Lipids study, said in a statement. "Now, for the first time, patients have an oral PCSK9 inhibitor for LDL lowering."
The approval was based on two Phase 3 trials from Merck's CORALreef program. In CORALreef Lipids, which enrolled 2,904 patients, Lipfendra reduced LDL cholesterol by 56 percent compared with placebo at 24 weeks. In CORALreef HeFH, which enrolled 303 patients with familial hypercholesterolemia, the drug cut LDL by 59 percent versus placebo at the same timepoint. The drug also lowered non-HDL cholesterol and apolipoprotein B, additional markers tied to cardiovascular disease risk.
The approval gives Merck a foothold in a market dominated by injectable PCSK9 inhibitors such as Amgen's Repatha and Regeneron and Sanofi's Praluent. About one in four US adults have high LDL cholesterol, according to the American Heart Association. Scotiabank analyst Louise Chen had said ahead of the approval that Lipfendra could have peak sales potential of tens of billions of dollars.
The drug's safety profile in the CORALreef Lipids trial was similar to placebo, Merck said. In the HeFH trial, the most common adverse reactions occurring at higher rates than placebo were dizziness, at 9 percent for Lipfendra versus 4 percent for placebo, and diarrhea, at 7 percent versus 2 percent. Similar proportions of patients in both groups stopped taking the drug due to adverse reactions.
Lipfendra received the FDA commissioner's National Priority Voucher, a program that accelerates regulatory review for drugs deemed essential to public health. An ongoing cardiovascular outcomes trial, CORALreef Outcomes, has completed enrollment with more than 14,500 participants and is studying whether Lipfendra reduces cardiovascular morbidity and mortality.
The approval strengthens Merck's pipeline as the company faces a major revenue challenge from Keytruda, its flagship cancer immunotherapy, which is set to encounter biosimilar competition after its patent protections begin expiring in 2028. Merck reported first-quarter Keytruda sales of $8.03 billion, up 12 percent year over year. Investors will watch enrollment updates from the CORALreef Outcomes trial for evidence of cardiovascular benefit.
This article is for informational purposes only and does not constitute investment advice.
