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

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

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 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2025 ➔ Jan 2025 | Trial primary completion date: Jun 2025 ➔ Jan 2025

Trial completion date • Trial primary completion date • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB

Lipoprotein (a) and lipid-lowering treatment from the perspective of a cardiac surgeon. An impact on the prognosis in patients with aortic valve replacement and after heart transplantation. (PubMed, Int J Cardiol Cardiovasc Risk Prev) - "There is still no targeted therapy for Lp(a), however, drugs such as pelacarsen, olpasiran, zerlasiran, lepodisiran and muvalaplin are in clinical trials and have been shown to be effective in significantly reducing Lp(a) levels. Therefore, the assessment of Lp(a) concentration in these patients will allow for a more accurate stratification of their cardiovascular risk, and the possibility of lowering Lp(a) will allow for the optimization of this risk. In this article, we summarized the most important information regarding the role of Lp(a) and lipid-lowering treatment in patients after AVR and HTx."

Journal • Cardiovascular • Transplantation

Therapeutic Potential of Lipoprotein(a) Inhibitors. (PubMed, Drugs) - "Early studies of antisense oligonucleotides (e.g., mipomersen, pelacarsen), RNA interference (e.g., olpasiran, zerlasiran, lepodisiran) and small molecule inhibitors (e.g., muvalaplin) have demonstrated effective Lp(a) lowering and good tolerability. These agents are moving forward in clinical development, in order to determine whether Lp(a) lowering reduces cardiovascular risk. The results of these studies have the potential to transform our approach to the prevention of cardiovascular disease."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia

New insights into the therapeutic options to lower lipoprotein(a). (PubMed, Eur J Clin Invest) - "If the results from the cardiovascular outcome trials, designed to demonstrate whether the reduction of Lp(a) of more than 80% as observed with pelacarsen, olpasiran or lepodisiran translates into the decrease of cardiovascular mortality and major adverse cardiovascular events, will be positive, lowering Lp(a) will become a new additional target in the management of patients with elevated cardiovascular risk."

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

Elevated Lipoprotein(a) Levels: A Crucial Determinant of Cardiovascular Disease Risk and Target for Emerging Therapies. (PubMed, Curr Probl Cardiol) - "Newly emerging therapies, including pelacarsen, zerlasiran, olpasiran, muvalaplin, and lepodisiran, show promise in significantly lowering Lp(a) levels, potentially transforming the management of cardiovascular disease. However, further research is essential to assess these novel therapies' long-term efficacy and safety, heralding a new era in cardiovascular disease prevention and treatment and providing hope for at-risk patients."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Disorders • Inflammation • Thrombosis

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 primary completion date: Sep 2028 ➔ Jan 2029

Trial primary completion date

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 | Not yet recruiting ➔ Recruiting

Enrollment open

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 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB

Targeting Lipoprotein(a): Can RNA Therapeutics Provide the Next Step in the Prevention of Cardiovascular Disease? (PubMed, Cardiol Ther) - "Promising treatment approaches targeting apo(a) expression include RNA-based drugs such as pelacarsen, olpasiran, SLN360, and lepodisiran, which are currently in clinical trials. In this comprehensive review, we provide a detailed overview of RNA-based therapeutic approaches and discuss the recent advances and challenges of RNA therapeutics specifically designed to reduce Lp(a) levels and thus the risk of cardiovascular disease."

Journal • Review • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Dyslipidemia • Heart Failure • APOB