Merck’s once-daily pill is the first oral PCSK9 inhibitor to hit the market for high cholesterol, beating AstraZeneca in the race to develop more accessible treatment options.
Merck has secured the first FDA approval for a once-daily oral PCSK9 inhibitor, a drug designed to lower “bad” LDL cholesterol without the need for an injection.
The FDA greenlight is for enlicitide, to be sold as Lipfendra for adults with high levels of LDL cholesterol and paired with diet and exercise. With Lipfendra, Merck has beat AstraZeneca to market. The U.K. pharma giant is developing its own oral PCSK9 candidate, dubbed AZD0780.
A macrocyclic peptide, Lipfendra was approved under the FDA’s Commissioner’s National Priority Voucher (CNPV) program, an initiative launched under former commissioner Marty Makary that is designed to speed up reviews for medicines and companies aligned with certain U.S. government priorities. Lipfendra represents the FDA’s ninth CNPV approval, per BioSpace tracking.
The approval was supported by a pair of Phase 3 trials from Merck’s CORALreef program, one of which included patients with heterozygous familial hypercholesterolemia (HeFH), a genetic disorder that causes high LDL levels. In that trial, Lipfendra significantly reduced LDL cholesterol by a placebo-adjusted 59% at 24 weeks, while lowering LDL cholesterol by 56% in a trial of adults with hypercholesterolemia.
For patients without the genetic condition, the drug’s safety profile was similar to that of placebo, while the most common adverse event for those with HeFH was diarrhea.
“LIPFENDRA’s label is the cleanest in the PCSK9 class, carrying zero contraindications or hypersensitivity warnings, unlike currently approved injectable competitors (Repatha, Praluent, and Leqvio), which are each contraindicated in patients with prior serious hypersensitivity reactions,” RBC Capital Markets wrote in a Thursday note to investors.
In an add-on trial, Lipfendra significantly outperformed other oral non-statin drugs Nexletol and Zetia in patients with hypercholesterolemia.
“This is a pivotal moment as we bring the first U.S. FDA-approved oral PCSK9 inhibitor to adults with high LDL-C, offering patients an important new option,” Dean Li, Merck’s R&D head, said in a Thursday announcement. “We’re proud of our work with regulators on this rigorous and efficient review process.”
RBC Capital Markets estimate peak sales of around $5 billion by 2034 for Lipfendra. Merck is launching the drug for $315 per month, representing a “meaningful discount” to injectable PCSK9 inhibitors, which range from $500–$600 a month.
Merck is also evaluating Lipfendra for its effect on cardiovascular morbidity and mortality.
