Merck & Co. has completed a hat trick of phase 3 victories for its oral PCSK9 inhibitor. Navigating into the broader hyperlipidemia population, the drugmaker stayed out of the shoals and charted a course to talks with regulators with another win for its CORALreef program.
The latest data come from a phase 3 trial that randomized adults with high cholesterol to receive the oral PCSK9 inhibitor enlicitide decanoate or placebo. Participants were taking stable lipid-lowering therapies, including a statin, and either had a history of a major atherosclerotic cardiovascular disease event or an increased risk for a first event.
After 24 weeks of once-daily oral dosing, low-density lipoprotein cholesterol (LDL-C) was significantly lower in the enlicitide arm than in the control group, achieving the trial’s primary endpoint, Merck said in a Sept. 2 release. The drugmaker reported wins on secondary endpoints that looked at levels of other lipoproteins, as well.
The readout follows the delivery of top-line data from a pair of phase 3 trials of enlicitide in other patient populations. Merck plans to discuss the data with regulatory agencies as it works to make enlicitide the first approved oral inhibitor of PCSK9. In a statement Tuesday, Dean Li, M.D., Ph.D., president of Merck Research Laboratories, discussed where enlicitide will fit into the treatment landscape if the drug candidate comes to market.
“The advent of injectable PCSK9 inhibitors has enabled a new approach to controlling LDL-C and reducing the risk of atherogenic cardiovascular events,” Li said. “Enlicitide, designed to deliver antibody-like efficacy, is the first oral macrocyclic peptide PCSK9 inhibitor with clinically meaningful and statistically significant LDL-C lowering in phase 3 trials.”
Amgen’s Repatha and Sanofi-Regeneron’s Praluent have long controlled the PCSK9 market. Those antibodies, as well as Novartis’ more recently approved siRNA drug Leqvio, are injected. The apparent lack of binding sites on the protein held back efforts to develop oral PCSK9 inhibitors.
Both Merck and AstraZeneca appear to have found ways around the problem. Merck is using its macrocyclic peptide enlicitide, while AstraZeneca has a small molecule that binds to a novel pocket. Merck’s three phase 3 wins put it at the front of the oral PCSK9 inhibitor race. AstraZeneca, having started three phase 3 trials this year, is tucked in behind its rival.
Li was bullish when discussing the competition on an earnings call in July, telling analysts enlicitide “will not just be first, it will be the best in relationship to everything that we've seen from competitor data."
The company is betting big on that belief, notably through a cardiovascular outcomes trial that has enrolled more than 14,500 people. Merck also sees opportunities to use enlicitide in drug combinations.