The US Food and Drug Administration has approved Merck & Co.’s cyclic peptide enlicitide decanoate for the reduction of low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia. The drug, which will be marketed as Lipfendra, is the first pill-based inhibitor of PCSK9—a protein that regulates blood cholesterol levels—to be approved. Financial analysts say the drug has the potential to generate over $2 billion in annual sales after a few years on the market.
“Macrocyclic peptides are having a moment,” according to a recent analysis by C&EN and CAS, a division of the American Chemical Society. The small, looped amino acid chains combine the specificity of biologics with the bioavailability of small-molecule drugs.
Lipfendra will be dosed in 20 mg tablets. Pharmaceutical companies and their R&D teams have pursued PCSK9 inhibition for nearly 20 years and with a range of different drug modalities. But until now the only approved drugs that target the protein have had to be injected.
In a Merck news release accompanying the approval, Dean Y. Li, president of Merck Research Laboratories, says, “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.”
The new drug is one that the FDA fast-tracked through its National Priority Voucher program. The program was a key initiative of former Commissioner Marty Makary, but critics have called for the program to be reformed. Li characterized the review process for Lipfendra as “rigorous and efficient” in his published statement.
Laura Howes is the Executive Editor for life sciences at C&EN.
