Current Clinical Trials for Treating Elevated Lipoprotein(a)

Nicholls SJ, Nissen SE, Fleming C, Urva S, Suico J, Berg PH, et al. Muvalaplin, an oral small molecule inhibitor of lipoprotein(a) formation: a Randomized Clinical Trial. JAMA. 2023;330(11):1042–53. https://doi.org/10.1001/jama.2023.16503.

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Nissen SE, Wolski K, Balog C, Swerdlow DI, Scrimgeour AC, Rambaran C, et al. Single Ascending Dose Study of a Short Interfering RNA Targeting Lipoprotein(a) Production in Individuals With Elevated Plasma Lipoprotein(a) Levels. JAMA. 2022;327(17):1679–87. https://doi.org/10.1001/jama.2022.5050

Kaur G, Abdelrahman K, Berman AN, Biery DW, Shiyovich A, Huck D, et al. Lipoprotein(a): Emerging insights and therapeutics. Am J Prev Cardiol. 2024;18:100641. https://doi.org/10.1016/j.ajpc.2024.100641

Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, et al. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020;382(16):1507-19. https://doi.org/10.1056/NEJMoa1912387

O’Donoghue ML, Fazio S, Giugliano RP, Stroes ESG, Kanevsky E, Gouni-Berthold I, et al. Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk. Circulation. 2019;139(12):1483–92. https://doi.org/10.1161/CIRCULATIONAHA.118.037184

Schwartz GG, Szarek M, Bittner VA, Diaz R, Goodman SG, Jukema JW, et al. Lipoprotein(a) and benefit of PCSK9 inhibition in patients with nominally controlled LDL cholesterol. J Am Coll Cardiol. 2021;78(5):421–33. https://doi.org/10.1016/j.jacc.2021.04.102.

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Gianos E, Duell PB, Toth PP, Moriarty PM, Thompson GR, Brinton EA, et al. Lipoprotein apheresis: utility, outcomes, and implementation in clinical practice: a Scientific Statement from the American Heart Association. Arterioscler Thromb Vasc Biol. 2024;44(12):e304–21. https://doi.org/10.1161/ATV.0000000000000177.

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Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925-46. https://doi.org/10.1093/eurheartj/ehac361

Koschinsky ML, Bajaj A, Boffa MB, Dixon DL, Ferdinand KC, Gidding SS, et al. A focused update to the 2019 NLA scientific statement on use of lipoprotein(a) in clinical practice. J Clin Lipidol. 2024;18(3):e308-e19. https://doi.org/10.1016/j.jacl.2024.03.001

Burgess S, Ference BA, Staley JR, Freitag DF, Mason AM, Nielsen SF, et al. Association of LPA variants with Risk of Coronary Disease and the implications for lipoprotein(a)-Lowering therapies: a mendelian randomization analysis. JAMA Cardiol. 2018;3(7):619–27. https://doi.org/10.1001/jamacardio.2018.1470.

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Albers JJ, Kennedy H, Marcovina SM. Evidence that Lp[a] contains one molecule of apo[a] and one molecule of apoB: evaluation of amino acid analysis data. J Lipid Res. 1996;37(1):192–6.

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Dana H, Chalbatani GM, Mahmoodzadeh H, Karimloo R, Rezaiean O, Moradzadeh A, et al. Molecular mechanisms and Biological functions of siRNA. Int J Biomed Sci. 2017;13(2):48–57.

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Hu B, Zhong L, Weng Y, Peng L, Huang Y, Zhao Y, et al. Therapeutic siRNA: state of the art. Signal Transduct Target Ther. 2020;5(1):101. https://doi.org/10.1038/s41392-020-0207-x.

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Sosnowska B, Surma S, Banach M. Targeted treatment against Lipoprotein (a): the coming breakthrough in lipid lowering therapy. Pharmaceuticals (Basel). 2022;15(12). https://doi.org/10.3390/ph15121573.

Dyrbus K, Gasior M, Penson P, Ray KK, Banach M. Inclisiran-New hope in the management of lipid disorders? J Clin Lipidol. 2020;14(1):16–27. https://doi.org/10.1016/j.jacl.2019.11.001.

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Zhang Y, Chen H, Hong L, Wang H, Li B, Zhang M, et al. Inclisiran: a new generation of lipid-lowering siRNA therapeutic. Front Pharmacol. 2023;14:1260921. https://doi.org/10.3389/fphar.2023.1260921.

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Leiter LA, Teoh H, Kallend D, Wright RS, Landmesser U, Wijngaard PLJ, et al. Inclisiran lowers LDL-C and PCSK9 irrespective of diabetes status: the ORION-1 Randomized Clinical Trial. Diabetes Care. 2019;42(1):173–6. https://doi.org/10.2337/dc18-1491.

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Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I, Tardif JC, Baum SJ, Steinhagen-Thiessen E, et al. Lipoprotein(a) reduction in persons with Cardiovascular Disease. N Engl J Med. 2020;382(3):244–55. https://doi.org/10.1056/NEJMoa1905239.

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Tsimikas S, Viney NJ, Hughes SG, Singleton W, Graham MJ, Baker BF, et al. Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study. Lancet. 2015;386(10002):1472–83. https://doi.org/10.1016/S0140-6736(15)61252-1.

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Viney NJ, van Capelleveen JC, Geary RS, Xia S, Tami JA, Yu RZ, et al. Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials. Lancet. 2016;388(10057):2239–53. https://doi.org/10.1016/S0140-6736(16)31009-1.

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Tsioulos G, Kounatidis D, Vallianou NG, Poulaki A, Kotsi E, Christodoulatos GS, et al. Lipoprotein(a) and atherosclerotic Cardiovascular Disease: where do we stand? Int J Mol Sci. 2024;25(6). https://doi.org/10.3390/ijms25063537.

ClinicalTrials.gov. NCT04023552, Assessing the Impact of Lipoprotein (a) Lowering With Pelacarsen (TQJ230) on Major Cardiovascular Events in Patients With CVD (Lp(a)HORIZON). 2019 https://clinicaltrials.gov/study/NCT04023552. Accessed November 11, 2024.

Milosavljevic MN, Stefanovic SM, Pejcic AV. Potential novel RNA-Targeting agents for effective lipoprotein(a) lowering: a systematic Assessment of the evidence from completed and Ongoing Developmental clinical trials. J Cardiovasc Pharmacol. 2023;82(1):1–12. https://doi.org/10.1097/FJC.0000000000001429.

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Koren MJ, Moriarty PM, Baum SJ, Neutel J, Hernandez-Illas M, Weintraub HS, et al. Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a). Nat Med. 2022;28(1):96–103. https://doi.org/10.1038/s41591-021-01634-w.

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ClinicalTrials.gov. NCT03626662, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a). 2018. Available at https://clinicaltrials.gov/study/NCT03626662. Accessed November 5, 2024.

Sohn W, Winkle P, Neutel J, Wu Y, Jabari F, Terrio C, et al. Pharmacokinetics, Pharmacodynamics, and tolerability of Olpasiran in healthy Japanese and non-japanese participants: results from a phase I, Single-dose, open-label study. Clin Ther. 2022;44(9):1237–47. https://doi.org/10.1016/j.clinthera.2022.07.008.

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O’Donoghue ML, Rosenson RS, Gencer B, Lopez JAG, Lepor NE, Baum SJ, et al. Small interfering RNA to reduce lipoprotein(a) in Cardiovascular Disease. N Engl J Med. 2022;387(20):1855–64. https://doi.org/10.1056/NEJMoa2211023.

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ClinicalTrials.gov. NCT05581303, Olpasiran Trials of Cardiovascular Events and Lipoprotein(a) Reduction (OCEAN(a)) - Outcomes Trial. 2022. Available at https://clinicaltrials.gov/study/NCT05581303. Accessed November 6, 2024.

ClinicalTrials.gov. NCT04606602, Study to Investigate Safety, Tolerability, PK and PD Response of SLN360 in Subjects With Elevated Lipoprotein(a). 2020. Available at https://clinicaltrials.gov/study/NCT04606602. Accessed November 8, 2024.

Nissen SE, Wolski K, Watts GF, Koren MJ, Fok H, Nicholls SJ, et al. Single ascending and multiple-dose trial of Zerlasiran, a short interfering RNA targeting lipoprotein(a): a Randomized Clinical Trial. JAMA. 2024;331(18):1534–43. https://doi.org/10.1001/jama.2024.4504.

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ClinicalTrials.gov. NCT05537571, Evaluate SLN360 in Participants With Elevated Lipoprotein(a) at High Risk of Atherosclerotic Cardiovascular Disease Events. 2023. Available at https://clinicaltrials.gov/study/NCT05537571. Accessed November 8, 2024.

Nissen SE, Wang Q, Nicholls SJ, Navar AM, Ray KK, Schwartz GG, et al. Zerlasiran-A Small-interfering RNA targeting lipoprotein(a): a phase 2 Randomized Clinical Trial. JAMA. 2024. https://doi.org/10.1001/jama.2024.21957.

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Nissen SE, Linnebjerg H, Shen X, Wolski K, Ma X, Lim S, et al. Lepodisiran, an extended-duration short interfering RNA targeting lipoprotein(a): a randomized dose-ascending clinical trial. JAMA. 2023;330(21):2075–83. https://doi.org/10.1001/jama.2023.21835.

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ClinicalTrials.gov. NCT05565742, a study of LY3819469 in participants with elevated lipoprotein(a) [Lp(a)]. 2022. Available at https://clinicaltrials.gov/ct2/show/NCT05565742. Accessed October 28, 2024.

ClinicalTrials.gov. NCT06292013, A Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events in Adults With Elevated Lipoprotein(a) - ACCLAIM-Lp(a). 2024 https://clinicaltrials.gov/study/NCT06292013. Accessed December 6, 2024.

ClinicalTrials.gov. NCT05563246, A Study of LY3473329 in Adult Participants With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events (KRAKEN). 2022. Available at https://clinicaltrials.gov/study/NCT05563246. Accessed November 9, 2024.

ClinicalTrials.gov. NCT04472676, A Study of LY3473329 in Healthy Participants. 2020. Available at https://clinicaltrials.gov/study/NCT04472676. Accessed November 11, 2024.

Hooper AJ, Fernando PMS, Burnett JR. Potential of muvalaplin as a lipoprotein(a) inhibitor. Expert Opin Investig Drugs. 2024;33(1):5–7. https://doi.org/10.1080/13543784.2024.2302592.

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Nicholls SJ, Ni W, Rhodes GM, Nissen SE, Navar AM, Michael LF, et al. Oral muvalaplin for lowering of lipoprotein(a): a Randomized Clinical Trial. JAMA. 2024. https://doi.org/10.1001/jama.2024.24017.

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