pelacarsen (AKCEA-APO(a)-LRx) / Ionis, Novartis, Royalty - LARVOL DELTA

Lipoprotein (a): A new target for pharmacological research and an option for treatment. (PubMed, Eur J Intern Med) - "Novel RNA-based therapies, including antisense oligonucleotides (pelacarsen) and small interfering RNAs (olpasiran, lepodisiran, zerlasiran)-have shown the potential to reduce Lp(a) levels by >80 %. The small oral molecule muvalaplin also shows promise in inhibiting Lp(a) formation...As new therapeutic options are developed that specifically target Lp(a), the inclusion of Lp(a) in cardiovascular risk assessment could improve stratification and lead to targeted interventions, particularly in high-risk populations. The growing body of genetic, epidemiological and clinical evidence makes Lp(a) a critical target in cardiovascular research and therapy."

Journal • Review • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Dyslipidemia • Familial Hypercholesterolemia • Heart Failure • Peripheral Arterial Disease

Pelacarsen reduces the need for lipoprotein apheresis in patients with elevated lipoprotein(a) and cardiovascular disease: The Phase 3 Lp(a)FRONTIERS APHERESIS trial (ESC-WCC 2025) - No abstract available

Clinical • P3 data • Cardiovascular

Lp(a) in daily clinical routine: risk-factor for both cardiovascular events and heart-failure? A retrospective analysis of the Luebeck Lp(a) heart-failure (HF) registry in patients after myocardial infarction. (PubMed, Atheroscler Plus) - "Despite ESC recommendation, routine Lp(a) measurement is only rarely performed even in a high-risk patient collective. In patients with MI, we could retrospectively not observe a correlation between Lp(a) levels and heart failure, as assessed by surrogate markers as EF and NTproBNP."

Journal • Retrospective data • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Hypertension • Metabolic Disorders • Myocardial Infarction • Obesity

Lp(a) Lowering Study of Pelacarsen (TQJ230) in US Black/African American and Hispanic Participants With Elevated Lp(a) and Established ASCVD (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Mar 2027 ➔ Mar 2026 | Trial primary completion date: Mar 2027 ➔ Mar 2026

Trial completion date • Trial primary completion date • Atherosclerosis • Cardiovascular

Cardiovascular risk management beyond statins: review of new therapies available in Italy. (PubMed, Egypt Heart J) - "This review underscores the evolving landscape of lipid-lowering therapies, with emphasis on agents acting through novel mechanisms beyond statin pathways. Bempedoic acid, by inhibiting ACLY and increasing LDL receptor expression, represents a safe and effective option for reducing LDL-C, especially in statin-intolerant individuals. PCSK9 inhibitors further expand therapeutic options by augmenting LDL receptor recycling and clearance. The integration of these agents into clinical practice may help mitigate residual cardiovascular risk and personalize treatment strategies in dyslipidemia management."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOA1

ADD-VANTAGE: Lp(a) Lowering Study of Pelacarsen (TQJ230) With Background Inclisiran in Participants With Elevated Lp(a) and Established ASCVD (clinicaltrials.gov) - P3 | N=340 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Atherosclerosis • Cardiovascular

Lipoprotein(a) and Cardiovascular Risk in Asian Populations: A Comprehensive Review. (PubMed, J Lipid Atheroscler) - "Novel therapeutic agents, including proprotein convertase subtilisin/kexin type 9 inhibitors, inclisiran, and antisense oligonucleotides such as pelacarsen, have demonstrated promising effects in lowering Lp(a). Given the high burden of cardiovascular disease and ethnic variability in Lp(a) distribution and genetic determinants, routine measurement of Lp(a) could improve risk stratification and therapeutic decision-making. This review summarizes current evidence regarding the epidemiology, genetic background, clinical relevance, and emerging therapeutic strategies targeting Lp(a) in Asian populations, highlighting the need for population-specific thresholds and further research to guide clinical practice."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Ischemic stroke • Myocardial Infarction

Managed Access Programs for TQJ230, Pelacarsen (clinicaltrials.gov) - P=N/A | N=0 | Available | Sponsor: Novartis Pharmaceuticals

New trial • Atherosclerosis • Cardiovascular

Lp(a)-Lowering Agents in Development: A New Era in Tackling the Burden of Cardiovascular Risk? (PubMed, Pharmaceuticals (Basel)) - "Such drugs include pelacarsen (an injectable ASO) and olpasiran, zerlasiran, and lepodisiran (injectable siRNA agents). Muvalaplin represents another therapeutic option to lower Lp(a) levels, since it is an oral selective small molecule inhibitor of Lp(a) formation, thus potentially exerting certain advantages in terms of its clinical use...The phase 3 CV trial outcomes are ongoing for some of these agents (i.e., pelacarsen, olpasiran, and lepodisiran) and are briefly mentioned. Overall, there is an urgent need for evidence-based guidelines on Lp(a) reduction in daily clinical practice, following the results of the phase 3 CV trials, as well as for establishing the ideal Lp(a) quantification method (i.e., using an apo(a) isoform-independent assay with appropriate calibrators, reporting the Lp(a) level in molar units)."

Journal • Review • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Heart Failure

An Open Label Extension (OLE) Study to Evaluate Long-term Safety and Tolerability of Pelacarsen (TQJ230) (clinicaltrials.gov) - P3 | N=41 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=60 ➔ 41

Enrollment change • Enrollment closed • Cardiovascular • Dyslipidemia • Metabolic Disorders

Design and rationale of Lp(a)HORIZON trial: Assessing the effect of Lipoprotein(a) lowering with Pelacarsen on major cardiovascular events in patients with CVD and elevated Lp(a). (PubMed, Am Heart J) - P3 | "Lp(a) HORIZON will determine the effect of pelacarsen on cardiovascular morbidity and mortality in patients with elevated Lp(a) and established CVD."

Journal • Atherosclerosis • Cardiovascular • Ischemic stroke • Myocardial Infarction • Peripheral Arterial Disease • APOB

A Multicenter Trial Assessing the Impact of Lipoprotein(a) Lowering With Pelacarsen (TQJ230) on the Progression of Calcific Aortic Valve Stenosis (clinicaltrials.gov) - P2 | N=502 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2029 ➔ Mar 2030 | Trial primary completion date: Jan 2029 ➔ Mar 2030

Trial completion date • Trial primary completion date

Therapeutic advances in the Lp(a) battle: what do we know and what are the most awaited novelties in the field ? (PubMed, Curr Opin Lipidol) - "The RNA-based agents pelacarsen, olpasiran, and lepodisiran represent the most advanced developments in this field. Ongoing Phase 3 trials, expected to be finalized between 2025 and 2029, will be crucial in determining their efficacy in improving cardiovascular outcomes and their safety profiles."

Journal • Cardiovascular • Myocardial Infarction

Pelacarsen Open-label Roll-over Extension Program' (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P3 trial • Atherosclerosis • Cardiovascular

A Multicenter Trial Assessing the Impact of Lipoprotein(a) Lowering With Pelacarsen (TQJ230) on the Rate of Weekly Lipoprotein Apheresis Sessions in Patients With Hyperlipoproteinemia(a) and Established Cardiovascular Disease in Germany (clinicaltrials.gov) - P3 | N=51 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB

Novel RNA-Based Therapies in the Management of Dyslipidemias. (PubMed, Int J Mol Sci) - "This article discusses the latest data from completed and ongoing trials on RNA therapies for dyslipidemia, including inclisiran, pelacarsen, olpasiran, zerlasiran, lepodisiran, volanesorsen, olezarsen, plozasiran, zodasiran, and solbinsiran. Each therapy targets specific molecules while also significantly impacting other lipid parameters. The promising results of these trials indicate potential improvements in lipid therapy and cardiovascular risk reduction, with ongoing studies expected to further refine the role of the novel RNA-based agents in effective lipid management."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • ANGPTL3

Lp(a)HORIZON: Assessing the Impact of Lipoprotein (a) Lowering With Pelacarsen (TQJ230) on Major Cardiovascular Events in Patients With CVD (clinicaltrials.gov) - P3 | N=8323 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: May 2025 ➔ Feb 2026 | Trial primary completion date: May 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Cardiovascular

Perspectives on early health economic evaluations of RNA therapies targeted at lipoprotein(a). (PubMed, Curr Opin Endocrinol Diabetes Obes) - "Early economic evaluations estimate longer-term clinical benefits and cost consequences associated with new medications.Existing casual evidence of Lp(a) and cardiovascular disease can be used in early economic evaluations as best available evidence, while awaiting results from major cardiovascular outcomes trials."

HEOR • Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Heart Failure

ADD-VANTAGE: Lp(a) Lowering Study of Pelacarsen (TQJ230) With Background Inclisiran in Participants With Elevated Lp(a) and Established ASCVD (clinicaltrials.gov) - P3 | N=340 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P3 trial • Atherosclerosis • Cardiovascular

Lp(a): A Rapidly Evolving Therapeutic Landscape. (PubMed, Curr Atheroscler Rep) - "Pelacarsen and olpasiran are two novel RNA-based injectable therapies which are being studied in ongoing phase 3 clinical trials, with the earliest of these to be concluded in 2025...Other candidate drugs, such as Lepodisiran, Zerlasiran, and Muvalaplin, are also in early-stage development. While there are presently no Lp(a)-lowering drugs available for routine clinical use, several promising candidates are currently under investigation. If these prove to be effective in randomized clinical trials, they will expand the cardiovascular care armamentarium and will allow clinicians to treat a presently unmitigated cardiovascular risk factor."

Clinical • Journal • Review • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia

Effect of mild hepatic impairment on the pharmacokinetics of pelacarsen (AHA 2024) - P1 | "Pelacarsen Cmax, AUClast, and AUCinf were, on average, 7%, 37%, and 50% higher, respectively, in participants with mild HI versus matched controls. All 90% confidence intervals around the HI versus healthy control geometric mean ratios included 1 (Table). The ranges of all PK parameters and estimated half-lives were similar between groups."

PK/PD data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • ASGR

Early health technology assessment of gene silencing therapies for lowering lipoprotein(a) in the secondary prevention of coronary heart disease. (PubMed, J Clin Lipidol) - P3 | "This early health technology assessment model used inclusion criteria from clinical trials. Olpasiran and pelacarsen would be cost-effective if annual treatment prices were AU$1867 and AU$984 respectively, from the Australian healthcare perspective."

Journal • Cardiovascular • Coronary Artery Disease • Heart Failure

Expanding therapeutic options: overview of novel pharmacotherapies for dyslipidemia. (PubMed, Expert Opin Pharmacother) - "Optimizing the use of available first- and second-line lipid-lowering drugs allows us to adequately control low-density lipoprotein cholesterol (LDL-C) levels, even in statin-intolerant individuals and in patients at high and very high risk of developing cardiovascular diseases who must reach more aggressive LDL-C targets. The drugs under development will further improve our ability to manage the overall lipid-related cardiovascular disease risk and target other dyslipidemia biomarkers."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders

Lp(a) Lowering Study of Pelacarsen (TQJ230) in US Black/African American and Hispanic Participants With Elevated Lp(a) and Established ASCVD (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2027 ➔ Mar 2027 | Trial primary completion date: Jun 2027 ➔ Mar 2027

Enrollment open • Trial completion date • Trial primary completion date • Atherosclerosis • Cardiovascular • Dyslipidemia

Lipoprotein (a) and cerebrovascular disease. (PubMed, J Int Med Res) - "Lp(a) seems to play a significant role in the pathogenesis of arterial ischemic stroke in children because environmental thrombotic and atherogenic factors are generally not present.Phase 3 trials of novel Lp(a) targeting agents, such as pelacarsen and olpasiran, are anticipated to demonstrate their efficacy in reducing the incidence of stroke. Given the richness of the literature, new guidelines regarding Lp(a) screening and management in targeted populations are warranted to provide more effective primary and secondary prevention."

Journal • Review • Atherosclerosis • Cardiovascular • CNS Disorders • Dyslipidemia • Ischemic stroke • Pediatrics • Vascular Neurology