Dyslipidemia in 2025: Year in Review

Lipid management has evolved significantly in 2025, with the key approvals from the US Food and Drug Administration (FDA) of inclisiran and plozasiran and the major trial advances of olezarsen and enlicitide. Ischemic stroke, hypercholesterolemia, and LDL-C management have all received crucial new preventive or protective measures during the course of the year, providing new resources for historically underserved populations.

Given the amount of critical news from 2025, the editorial team at HCPLive has collected 13 of the most impactful headlines from the last 12 months, including FDA announcements, critical trial results, and key clinician insights. Catch up on anything you may have missed below.

FDA News

FDA Approves Inclisiran (Leqvio) Label Update as First-Line Monotherapy in Hypercholesterolemia

On July 31, 2025, inclisiran’s label was updated to allow its use as a first-line monotherapy, along with diet and exercise, to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia. Parent company Novartis announced the FDA’s proactive request of the label update, based on the robust LDL-C lowering data for PCSK9-targeting therapies. Prior to the update, inclisiran was required to be used on top of or in combination with statin therapy – the update also revised instances of “primary hyperlipidemia” to “hypercholesterolemia” to enhance focus on LDL-C reduction.

FDA Approves Plozasiran for Adults With Familial Chylomicronemia Syndrome

Plozasiran was approved on November 18, 2025, for the reduction of triglycerides in adult patients with familial chylomicronemia syndrome (FCS). The first-in-class RNA interference therapeutic is designed to reduce the production of apoC-III, a major component of triglyceride-rich lipoproteins and a regulator of triglyceride metabolism. The approval was based on the PALISADE trial, which saw patients receiving plozasiran exhibit an 80% median change in triglycerides from baseline and an 83% decreased risk of acute pancreatitis compared to placebo.

FDA Approves Lerodalcibep-liga (Lerochol) for LDL-C Reduction in Hypercholesterolemia

On December 15, 2025, the FDA approved lerodalcibep-liga, under the brand name Lerochol, as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). The novel, small protein-binding, third-generation PCSK9 inhibitor, designed as a once-monthly, single small-volume subcutaneous injections for LDL-C lowering, was approved on the back of the LIBerate program, a series of 5 phase 3 registration studies including 2900 patients.

Trial Updates and New Guidelines

CORALreef Lipids: Enlicitide Lowers LDL-C as Much as Injectables, With Ann Marie Navar, MD, PhD

The CORALreef Lipids phase 3 trial highlighted the efficacy of an oral, once-daily dose of PCSK9 inhibitor enlicitide in significantly reducing LDL-C compared to placebo in patients with hypercholesterolemia with or at risk of atherosclerotic cardiovascular disease (ASCVD). The 24-week trial compared enlicitide 20 mg to placebo, displaying an LDL-C reduction of ≤60% in the enlicitide cohort, which was maintained at 52 weeks. Patients also saw a 53% reduction in non-HDL, a 50% reduction in ApoB, and a 28% reduction in Lp(a).

CORE/CORE2: Olezarsen Achieves Primary Endpoint in Severe Hypertriglyceridemia

The phase 3 CORE and CORE2 trials both highlighted olezarsen’s capacity for substantial reductions in fasting triglyceride levels among patients with severe hypertriglyceridemia. The investigative antisense oligonucleotide slows triglyceride clearance by inhibiting lipoprotein lipase activity and the liver’s uptake of triglyceride-rich particles. During the trials, olezarsen demonstrated a placebo-adjusted mean reduction in fasting triglyceride of ≤72% at 6 months, which was sustained for the full 12-month trial period.

VICTORION-Difference: Inclisiran Achieves Primary Endpoint of LDL-C Reduction Versus Placebo

Patients with hypercholesterolemia at high or very high risk of cardiovascular events reached LDL-C goals with inclisiran on top of individually optimized lipid-lowering therapy than with placebo in the VICTORION-Difference trial. The small interfering ribonucleic acid targeting PCSK9 messenger RNA provides a consistent reduction in LDL-C when given twice yearly after initial doses. VICTORION-Difference saw 84.9% of patients in the inclisiran arm achieve guideline-recommended LDL-C goals compared to 31% receiving placebo.

Study Finds Icosapent Ethyl Can Reduce Cardiovascular Risk, Even in Well-Controlled LDL-C

The landmark REDUCE-IT trial further examined icosapent ethyl’s cardiovascular benefits for patients, regardless of their baseline LDL-C levels. The trial was the basis for icosapent ethyl’s 2019 FDA approval for reducing cardiovascular risk as an adjunct to maximally tolerated statin therapy in adults with triglyceride levels ≥150 mg/dL and established cardiovascular disease. This secondary analysis examined a composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina based on baseline LDL-C level.

Obicetrapib Achieves Robust LDL-C Reductions in Phase 3 ASCVD Trials

In the BROADWAY and TANDEM phase 3 trials, once-daily oral obicetrapib substantially reduced LDL-C in patients with ASCVD when used as an adjunct to statins. The BROADWAY trial saw obicetrapib achieve a 33% reduction in LDL-C on top of maximally tolerated lipid-lowering therapies, along with a 21% relative reduction in major adverse cardiovascular events. TANDEM saw a fixed-dose combination of obicetrapib and ezetimibe meet all primary endpoints for LDL-C reduction compared with placebo.

Feature Content/Podcasts

RX Review: Updates and Unmet Needs for Familial Chylomicronemia Syndrome

In the first of a 7-part video series discussing recent changes in therapeutic options for patients with FCS, host Viet Le, DMSc, PA-C, a preventive cardiology PA at Intermountain Health and former president of the Academy of Physician Associates in Cardiology, spoke with Christie Ballantyne, MD, chief of cardiovascular research at Baylor College of Medicine and principle investigator in the PALISADE trial, to highlight the challenges and treatment gaps present in FCS care. However, Ballantyne ultimately marks 2025 as a turning point for FCS, with the approval of plozasiran on November 18 and olezarsen’s approval in late 2024 providing targeted therapies capable of substantially reducing triglycerides.

RX Review: Integrating New Therapies in FCS Treatment Algorithms

In the fourth part of this 7-part series, host Viet Le, DMSc, PA-C, and guest Christie Ballantyne, MD, discuss plozasiran and its newfound role in contemporary FCS management. Ballantyne discusses the mechanism of action of small interfering RNA therapies like plozasiran and how they modulate pathways independent of lipoprotein lipase activity. Additionally, the pair discuss how plozasiran expands treatment options in this historically underserved population.

RX Review: Understanding Plozasiran’s Role in FCS Management

In the fifth episode of this 7-part series, host Viet Le, DMSc, PA-C, and guest Christie Ballantyne, MD, discussed the effect olezarsen and plozasiran have had on treatment algorithms for FCS. While the approvals are groundbreaking, Ballantyne cautions careful attention when implementing the new medications, with particular attention to patient needs and existing management principles. He also emphasizes the importance of consistent lipid monitoring and clear communication across the various related specialties, including nutritionists, cardiologists, and lipid specialists.