Evolocumab

iStock, JHVEPhoto The cholesterol-lowering drug is part of a suite of medicines that also includes MariTide and that Amgen Chief Medical Officer Paul Burton hopes will make the company the “undisputed leader in the management of cardiometabolic risk for patients” by 2030. Heart disease is the leading cause of death in the U.S., and this weekend, Amgen presented Phase III data showing a significant step forward against a top killer: heart attacks. The VESALIUS-CV trial tested over 12,000 high-risk patients with atherosclerotic cardiovascular disease (ASCVD) or high-risk diabetes but with no history of heart attack or stroke. Patients received either Amgen’s PCSK9 inhibitor Repatha or placebo in addition to lipid-lowering therapy and were followed for approximately four and a half years. VESALIUS-CV met its primary endpoints, Amgen said during a presentation Saturday at the American Heart Association (AHA) Scientific Sessions in New Orleans, adding further detail to results first announced on Oct. 2. The addition of Repatha to standard treatment, statins or other low-density lipoprotein (LDL-C) lowering treatments reduced major adverse cardiovascular events (MACE)— death, heart attack or ischemic stroke—by 25%, and first heart attacks by around 36% compared to placebo. The treatment regimen also lowered LDL-C—aka “bad” cholesterol—to around 45 mg/dL on average, according to the presentation. There were no new safety signals. In an interview with BioSpace prior to the AHA meeting, Paul Burton, Amgen’s chief medical officer, described the results as “remarkable.” “I’ve been doing cardiometabolic drug development for 25 years, and I really think it’s just about the best dataset I’ve seen in those two and a half decades,” he said. “It’s clear. It’s unambiguous.” BMO Capital Markets’ analysts were similarly effusive. “While it may take time for full payer and physician adoption, we expect these results could be practice changing in cardiology, pushing for an earlier use of PCSK9 treatment in patients without optimal LDL-C control,” they wrote in a Sunday evening note to investors. The PCSK9 protein reduces the liver’s ability to remove LDL-C from the blood. First approved by the FDA in 2015 as an adjunct treatment for people with high LDL-C, Repatha inhibits this protein. With the results from VESALIUS-CV, Repatha “is now the first and only PCSK9 inhibitor shown to reduce cardiovascular events in high-risk adults without prior heart attack or stroke,” Jay Bradner, EVP of Research and Development at Amgen, said in a statement on Oct. 2. With these new data, Amgen is looking first to “clearly get the data in [Repatha’s] package insert and make it broadly available,” Burton said, and then to have the VESALIUS-CV trial population defined as a new indication. “I think that just carries more weight with systems, with payers here in the U.S. and around the world.” BMO added that while prior studies had demonstrated the benefit of PCSK9 inhibitor therapy in patients at a higher risk of MACE due to a prior cardiac event, “VESALIUS shows preventative benefits can stretch earlier into the treatment paradigm, potentially forcing physicians (and payers) to consider the merits of preventative PCSK9i therapy when increased risk markers are evident.” Cardiovascular disease Deep Dive: Cardiovascular Disease Back in the Spotlight In this deep dive, BioSpace explores the diverse therapeutic modalities now in development, as well as the opportunities and battles for market dominance in this emerging space. March 10, 2025 · 2 min read · Heather McKenzie A Cardiovascular Renaissance This year’s AHA takes place amid somewhat of a renaissance for the cardiovascular space. With key recent FDA approvals such as BridgeBio’s transthyretin amyloid cardiomyopathy drug Attruby and Novo Nordisk’s GLP-1 Wegovy to reduce cardiovascular events, and investor dollars being poured into biotech startups like Kardigan , America’s number one killer is again a key focus for biopharma. Burton had some thoughts on the drivers behind this rebound. “What we see now is this real intersection between biology becoming far more predictive of translating into management of human disease. We’ve got very highly specialized and innovative therapeutics . . . and we understand the patient journey and the disease process in patients so much better,” he said. When you bring these together, “we can now have very tailored therapies that impact huge populations of patients that have such a higher chance of success.” For Burton, the key to this success is access. “A surgeon general in this country once said that medicines don’t work in people who don’t take them,” he said. On this note, Amgen recently launched a new DTC platform called AmgenNow , where it is offering Repatha for $239 per month—a nearly 60% discount from the current wholesale acquisition cost of $527.70. In the development pipeline , Amgen is testing olpasiran, an siRNA that lowers lipoprotein(a), in a Phase III trial in patients with atherosclerotic cardiovascular disease. The primary completion date for this study is December 2026, according to Clinicaltrials.gov. And looming in Amgen’s pipeline, of course, is the much-discussed MariTide, which Burton said “not only is effective in reducing weight and BMI, but it has multiple cardiovascular benefits as well.” Amgen is currently studying the asset in a Phase III cardiovascular outcomes trial in patients with atherosclerotic cardiovascular disease and overweight or obesity. That study kicked off this summer and has a primary completion date of June 2028. Obesity Beyond MariTide: Amgen Makes Portfolio Play Amid Scrutiny of Obesity Prospect Suddenly one obesity asset has come to define Amgen but executives see a fuller portfolio that will bring the big biotech into the future. September 10, 2025 · 5 min read · Nick Paul Taylor “When you bring that suite of medicines together, clearly we need two more pieces of the puzzle to fall into place,” Burton said. “We need the outcome study of olpasiran to be positive, and we need the ongoing studies of MariTide to also be positive, but we have very strong Phase II data for both of them.” Burton is hopeful of having both MariTide and olpasiran approved “in the second half of this decade, and then I think we really will be the undisputed leader in the management of cardiometabolic risk for patients.”

iStock, Dragon Claws 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.