Multiple analyst firms were impressed by the Phase III data, which showed that Merck’s oral PCSK9 inhibitor can lower low-density lipoprotein cholesterol by more than 55% after 24 weeks.
Merck’s orally available PCSK9 inhibitor enlicitide decanoate aced a late-stage study, significantly lowering levels of “bad” cholesterol in adults with hypercholesterolemia and a history of heart disease.
The data, presented Saturday at the American Heart Association’s 2025 Scientific Sessions, come from the pivotal Phase III CORALreef Lipids trial, which enrolled more than 2,900 adults who have or are at risk of atherosclerotic cardiovascular disease and who were on background lipid-lowering treatments. At 24 weeks, a daily dose of oral enlicitide elicited a 55.8% reduction in low-density lipoprotein cholesterol (LDL-C) levels versus placebo—an effect Merck labeled as “statistically significant and clinically meaningful.”
Writing to investors Sunday afternoon, Stifel analysts called the readout “favorable,” adding that enlicitide’s performance looks “generally comparable to the injectables.”
Beyond LDL-C, Merck’s drug also elicited improvements in other lipid markers, including apolipoprotein B and lipoprotein(a), which dropped by 50.3% and 28.2%, respectively, at 24 weeks versus placebo. Merck on Saturday also presented one-year data, touting a 47.6% reduction in LDL-C among patients treated with enlicitide, as compared with placebo.
Enlicitide’s effects on lipoprotein(a) levels, in particular, were “generally consistent with what we’ve seen with the injectables,” Stifel wrote.
Analysts at BMO Capital Markets shared the sentiment, calling Saturday’s readout “impressive.” Enlicitide’s data, the analysts added, “continue to validate product LDL-C reductions with more benefits potentially providing combination opportunities.”
BMO also noted that Amgen’s data presented Saturday at AHA could set the stage for enlicitide’s future readouts. In the Phase III VESALIUS-CV study, the addition of Amgen’s own PCSK9 inhibitor Repatha, an injectable monoclonal antibody, to statins or other LDL-C therapies led to a 25% reduction in the risk of major adverse cardiovascular events (MACE) in high-risk patients with atherosclerotic cardiovascular disease or high-risk diabetes but with no history of heart attack or stroke. The Repatha-based combination also cut the risk of first heart attacks by roughly 36% and lowered LDL-C levels.
VESALIUS-CV’s findings, according to BMO, “derisk expected efficacy of enlicitide when thinking about potential benefits in CORALreef Outcomes,” another Phase III study being run by Merck, with primary completion date in November 2029. “With evolocumab [Repatha] showing clear benefits in the reduction of risk for MACE events, we expect similar results for enlicitide in the future, given similarities in their study designs.”
Analysts at Guggenheim Partners were likewise optimistic about enlicitide’s prospects, pointing specifically to Merck’s data point showing at least a 97% treatment adherence rate. “We see a path for enlicitide to exceed the ~ $2.8Bn consensus currently estimates for enlicitide in 2033,” the analysts wrote in a note on Sunday.
