Data presented at this year’s American Heart Association Scientific Sessions in New Orleans underline rapid advancements in the cardiovascular field.
As this year’s Scientific Sessions of the American Heart Association in New Orleans winds down, BioSpace rounds up some of the most impactful presentations, with a particular focus on novel modalities and drugs that break new efficacy barriers and open up new patient populations. Read below for more.
Amgen Targets Cardiometabolic Leadership With ‘Practice-Changing’ Repatha Data
Amgen arrived at AHA 2025 with detailed data from the Phase III VESALIUS-CV trial testing its lipid-lowering antibody Repatha—with the overarching goal of establishing itself as the “undisputed leader in the management of cardiometabolic risk” by 2030, according to chief medical officer Paul Burton.
VESALIUS-CV enrolled patients who had atherosclerotic cardiovascular disease or had high-risk diabetes, but who otherwise had a clean history of heart attack or stroke. In these patients, adding Repatha to statins or other agents used to lower low-density lipoprotein cholesterol (LDL-C) levels resulted in a 25% drop in the risk of major adverse cardiovascular disease.
The Repatha regimen also decreased the risk of first heart attacks by 36% and lowered overall LDL-C levels.
BMO Capital Markets analysts, in a Sunday evening note to investors, said they expect the results “could be practice changing in cardiology, pushing for an earlier use of PCSK9 treatment in patients without optimal LDL-C control.”
Amgen is looking to have Repatha’s label reflect these new data, Burton told BioSpace prior to the presentation, with the goal of making the drug “broadly available.” Eventually, the pharma also wants to have the study’s population defined as its own, new indication.
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Merck’s Cholesterol Pill Rivals Injectables
Merck also came to the meeting with Phase III findings, revealing that at 24 weeks, its orally available PCSK9 blocker enlicitide decanoate triggered a 55.8% decrease vs. placebo in LDL-C in adult patients with hypercholesterolemia.
Analysts were impressed with enlicitide’s data, with Stifel on Sunday saying the results look “generally comparable to the injectables.” Enlicitide was able to sustain its LDL-C benefits, keeping levels lower by 47.6% at 1 year when compared with placebo.
Aside from LDL-C, enlicitide also led to a 50.3% reduction in apolipoprotein B and a 28.2% drop in lipoprotein(a). Stifel was likewise positive about these biomarker improvements, noting that enlicitide’s effect on lipoprotein(a), in particular, was “generally consistent with what we’ve seen with the injectables.”
Merck did not reveal specific regulatory submission plans during its presentation Saturday, only noting that it will discuss these findings with authorities worldwide. If approved, however, enlicitide has the potential to be the first oral PCSK9 inhibitor for lowering LDL-C.
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Novo Nordisk Pushes Forward in ATTR-CM Despite Mixed Mid-Stage Data
Novo Nordisk’s investigational antibody coramitug significantly reduced levels of a key disease marker in a Phase II transtyretin amyloid cardiomyopathy (ATTR-CM) study—but only for one specific dose. Despite these mixed results, the Danish pharma appears determined to forge ahead with coramitug, according to a Monday report from Endpoints News.
“We hope to bring added value by introducing a new mode of action for people living with ATTR-CM,” Kees Hovingh, chief scientific advisor for medical and translational science at Novo, told Endpoints, adding that the pharma will take coramitug into late-stage development based on the totality of its findings.
Phase II data presented at AHA showed that the 60-mg/kg dose of coramitug led to a 48% placebo-adjusted reduction in concentrations of NT-proBNP, a key indicator used to diagnose ATTR-CM and gauge disease severity and prognosis. The lower 10-mg/kg dose, however, showed no such effect. Neither dose significantly improved results on the 6-minute walk test.
Novo had first announced its intention to take coramitug into Phase III in August, at the time announcing it would launch the late-stage program this year, with completion as early as 2028.
After Patient Death, Intellia Touts Long-Term Efficacy of CRISPR-Based Gene Therapy
Intellia Therapeutics’ investigational gene therapy nexiguran ziclumeran, also known as nex-z, elicited a sustained biomarker benefit in patients with ATTR-CM, according to Phase I data presented Saturday by the biotech at AHA 2025.
In 9 patients who were followed for at least 36 months, serum levels of the transthyretin protein dropped by an average of 87%, consistent with what had been observed for the entire study cohort at 24 months. Intellia also touted “evidence of disease stabilization or improvement” at 24 months versus baseline, as defined by sustained improvements in various blood and clinical indicators, including NT-proBNP and echocardiography findings.
In particular, nex-z was able to preserve functional status in 69% of treated patients at 24 months, as measured by the 6-minute walk test. The one-time gene therapy also resulted in better quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire.
These data come after Intellia last week reported that one patient who had been treated with nex-z died after developing life-threatening liver toxicities. In light of the safety signal, the FDA has placed a clinical hold on the company’s Phase III MAGNITUDE and MAGNITUDE 2 studies of the gene therapy, in ATTR-CM and ATTR with polyneuropathy, respectively. Intellia is currently working with the regulator to address the freeze, CEO John Leonard said in a Saturday statement.
CRISPR’s Gene Editor Shows ‘Compelling’ Cholesterol-Lowering Effect in Early Study
Also taking a gene-based approach to cardiovascular disease is CRISPR Therapeutics, which on Friday revealed that its CRISPR/Cas9-driven gene editor CTX310 cut triglyceride concentrations by 55% on average, hitting a maximum reduction of 84%.
Among those with elevated triglycerides at baseline—a concentration exceeding 150 mg/dL—the gene editor resulted in a mean 60% reduction in levels of the lipid. At the same time, CTX310 lowered LDL by 49% on average.
CTX310 also led to a 73% decline in circulating levels of the ANGPTL3 protein, known to be involved in the regulation of LDL and triglycerides.
In a note to investors on Monday, analysts at William Blair called CTX310’s efficacy “compelling,” noting that the LDL reductions are “competitive” with other investigational assets, while the gene editor’s impacts on triglyceride “potentially set a new bar in the space.”
CRISPR’s AHA 2025 readout “represents a significant positive development for the company” and positions CTX310 “as a potentially transformative one-time treatment for dyslipidemias,” William Blair added.
Ionis Sees ‘Game Changing’ Triglyceride Drop, Paves Path to FDA
Ionis Pharmaceuticals’ antisense oligonucleotide Tryngolza dropped patients’ fasting triglyceride levels by 72% in a Phase III study of hypertriglyceridemia, an effect that persisted out to 12 months of testing.
The company also reported that the treatment lowered acute pancreatitis events by 85% over the course of the trial. 89% of patients on a 50 mg dose of the drug also saw their triglyceride levels drop below 880 mg/dL, an indicator level of high risk of pancreatitis.
The company is planning an sBLA for Tryngolza by the end of the year, which William Blair analysts, writing on Monday, said “will likely be transformational for the treatment for sHTG [severe hypertriglyceridemia] across a potential broad spectrum of patients.”
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