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Review

Safety and efficacy of therapies for chylomicronemia

& ORCID Icon
Pages 395-405 | Received 08 May 2022, Accepted 21 Jun 2022, Published online: 03 Jul 2022

References

  • Brahm AJ, Hegele RA. Chylomicronaemia - current diagnosis and future therapies. Nat Rev Endocrinol. 2015;11:352–362.
  • Paquette M, Bernard S, Hegele RA, et al. Chylomicronemia: differences between familial chylomicronemia syndrome and multifactorial chylomicronemia. Atherosclerosis. 2019;283:137–142.
  • Chait A, Eckel RH. The chylomicronemia syndrome is most often multifactorial. Ann Intern Med. 2019;170:626–634.
  • Paragh G, Á N, and Harangi M, et al. Causes, clinical findings and therapeutic options in chylomicronemia syndrome, a special form of hypertriglyceridemia. Lipids Health Dis. 2022;21:21.
  • Williams L, Rhodes KS, Karmally W, et al. Familial chylomicronemia syndrome: bringing to life dietary recommendations throughout the life span. J Clin Lipidol. 2018;12:908–919.
  • Hegele RA, Pollex RL. Hypertriglyceridemia: phenomics and genomics. Mol Cell Biochem. 2009;326:35–43.
  • Hegele RA, Borén J, Ginsberg HN, et al. Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement. Lancet Diabetes Endocrinol. 2020;8(1):50–67.
  • Hegele RA, Ginsberg HN, Chapman MJ, et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014;2(8):655–666.
  • Nurmohamed NS, Dallinga–Thie GM, Stroes ESG. Targeting apoC-III and ANGPTL3 in the treatment of hypertriglyceridemia. Expert Rev Cardiovasc Ther. 2020;18(6):355–361.
  • Reeskamp LF, Tromp TR, Stroes ESG. The next generation of triglyceride-lowering drugs: will reducing apolipoprotein C-III or angiopoietin like protein 3 reduce cardiovascular disease? Curr Opin Lipidol. 2020;31:140–146.
  • Lazarte J, and Hegele RA. Volanesorsen for treatment of familial chylomicronemia syndrome. Expert Rev Cardiovasc Ther. 2021;19:685–693.
  • Witztum JL, Gaudet D, and Freedman SD, et al. Volanesorsen and triglyceride levels in familial chylomicronemia syndrome. N Engl J Med. 2019;381:531–542.
  • Kersten S. ANGPTL3 as therapeutic target. Curr Opin Lipidol. 2021;32:335–341.
  • Dron JS, Hegele RA. Genetics of hypertriglyceridemia. Front Endocrinol. 2020;11:455.
  • Hegele RA, Berberich AJ, Ban MR, et al. Clinical and biochemical features of different molecular etiologies of familial chylomicronemia. J Clin Lipidol. 2018;12:920–927.
  • Berberich AJ, Hegele RA. A modern approach to dyslipidemia. Endocr Rev. 2021;2:bnab037.
  • Laufs U, Parhofer KG, Ginsberg HN, et al. Clinical review on triglycerides. Eur Heart J. 2020;41:99–109.
  • Goldberg RB, Chait A. A comprehensive update on the chylomicronemia syndrome. Front Endocrinol. 2020;11:593931.
  • Baass A, Paquette M, Bernard S, et al., Familial chylomicronemia syndrome: an under-recognized cause of severe hypertriglyceridaemia. 2020;J Inter Med. 287:340–348.
  • Brown WV, Gaudet D, Goldberg I, et al. Roundtable on etiology of familial chylomicronemia syndrome. J Clin Lipidol. 2018;12:5–11.
  • Valdivielso P, Ramírez-Bueno A, Ewald N. Current knowledge of hypertriglyceridemic pancreatitis. Eur J Intern Med. 2014;25:689–694.
  • Gaudet D, Signorovitch J, Swallow E, et al. Medical resource use and costs associated with chylomicronemia. J Med Econ. 2013; 16: 657–666.
  • Sisman G, Erzin Y, Hatemi I, et al. Familial chylomicronemia syndrome related chronic pancreatitis: a single-center study. Hepatobiliary Pancreatic Dis Intl. 2014; 13: 209–214.
  • Nordestgaard BG, Benn M, Schnohr P, et al. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298:299–308.
  • Stroes E, Moulin P, Parhofer KG, et al. Diagnostic algorithm for familial chylomicronemia syndrome. Atherosclerosis Suppl. 2017;23:1–7.
  • Moulin P, Dufour R, Averna M, et al. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recommendations and proposal of an “FCS score.” Atherosclerosis. 2018;275:265–272.
  • Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22.
  • Nicholls SJ, Lincoff AM, Garcia M, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. JAMA. 2020;324(22):2268–2280.
  • Berberich AJ, Hegele RA. Secondary causes of chylomicronemia: defining the underside of the iceberg. J Intern Med. 2018;283:405–407.
  • Rouis M, Dugi KA, Previato L, et al. Therapeutic response to medium-chain triglycerides and ω-3 fatty acids in a patient with the familial chylomicronemia syndrome. Arterioscler Thromb Vasc Biol. 1997;17:1400–1406.
  • Ahmad Z, Wilson DP. Familial chylomicronemia syndrome and response to medium-chain triglyceride therapy in an infant with novel mutations in GPIHBP1. J Clin Lipidol. 2014;8:635–639.
  • Yadav D, Hawes RH, Brand RE, et al. Alcohol consumption, cigarette smoking, and the risk of recurrent acute and chronic pancreatitis. Arch Intern Med. 2009;169:1035–1045.
  • Jacobson TA, Maki KC, Orringer CE, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015; 9: S1–S122.e1.
  • Berberich AJ, Ziada A, Zou GY, et al. Conservative management in hypertriglyceridemia-associated pancreatitis. J Intern Med. 2019;286:644–650.
  • Inayat F, Zafar F, Baig AS, et al. Hypertriglyceridemic pancreatitis treated with insulin therapy: a comparative review of 34 cases. Cureus. 2018;10(10):548.
  • Chen Z, Huang X, Zhang M, et al. Rapid reduction in triglyceride levels by therapeutic plasma exchange in patients with hypertriglyceridemic pancreatitis. J Clin Apheresis. 2022;37:82–90.
  • Wolska A, Dunbar RL, Freeman LA, et al. Apolipoprotein C-II: new findings related to genetics, biochemistry, and role in triglyceride metabolism. Atherosclerosis. 2017;267:49–60.
  • Tremblay AJ, Lamarche B, Hogue J-C, et al. Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia. J Lipid Res. 2009;50(7):1463–1471.
  • Yuan G, Al-Shali KZ, Hegele RA. Hypertriglyceridemia: its etiology, effects and treatment. Can Med Assoc J. 2007;176:1113–1120.
  • Wolska A, Yang ZH, Remaley AT. Hypertriglyceridemia: new approaches in management and treatment. Curr Opin Lipidol. 2020;31:331–339.
  • Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384:626–635.
  • Kowa Research Institute, Inc. Kowa to discontinue K-877 (Pemafibrate) “Prominent” Cardiovascular outcomes study [Internet]. Chicago IL: Cision PR Newswire; April 2022. [cited 2022 May 28]. Available from: https://www.prnewswire.com/news-releases/kowa-to-discontinue-k-877-pemafibrate-prominent-cardiovascular-outcomes-study-301520956.html
  • Ganda OP. When to lower triglycerides? Curr Opin Lipidol. 2020;31:238–245.
  • Goldberg A, Alagona P, Capuzzi DM, et al. Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia. Am J Cardiol. 2000;85:1100–1105.
  • Gotto AM, Moon JE. Pharmacotherapies for lipid modification: beyond the statins. 2013;Nature Rev Cardiol. 10:560–570.
  • Sherratt SCR, Lero M, Mason RP. Are dietary fish oil supplements appropriate for dyslipidemia management? A review of the evidence. Curr Opin Lipidol. 2020;31:94–100.
  • Pschierer V, Richter WO, Schwandt P. Primary chylomicronemia in patients with severe familial hypertriglyceridemia responds to long-term treatment with (n-3) fatty acids. J Nutrition. 1995;125:1490–1494.
  • Richter WO, Jacob BG, Ritter MM, et al. Treatment of primary chylomicronemia due to familial hypertriglyceridemia by omega-3 fatty acids. Metabolism. 1992;41:1100–1105.
  • Bajaj A, Cuchel M. Homozygous familial hypercholesterolemia: what treatments are on the horizon? Curr Opin Lipidol. 2020;31:119–124.
  • Sacks FM, Stanesa M, Hegele RA. Severe hypertriglyceridemia with pancreatitis: thirteen years’ treatment with lomitapide. JAMA Intern Med. 2014;174(3):443–447.
  • Cuchel M, Meagher EA, du Toit Theron H, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013;381:40–46.
  • deGoma EM. Lomitapide for the management of homozygous familial hypercholesterolemia. Rev Cardiovasc Med. 2014;15:109–118.
  • Basu D, Goldberg IJ. Regulation of lipoprotein lipase-mediated lipolysis of triglycerides. Curr Opin Lipidol. 2020;31:154–160.
  • Hegele RA. Apolipoprotein C-III inhibition to lower triglycerides: one ring to rule them all? Eur Heart J. 2022;43:1413–1415.
  • Gouni-Berthold I. The role of antisense oligonucleotide therapy against apolipoprotein-CIII in hypertriglyceridemia. Atherosclerosis Suppl. 2017;30:19–27.
  • Hegele RA. Multidimensional regulation of lipoprotein lipase: impact on biochemical and cardiovascular phenotypes. J Lipid Res. 2016;57:1601–1607.
  • Qin W, Sundaram M, Wang Y, et al. Missense mutation in APOC3 within the C-terminal lipid binding domain of human ApoC-III results in impaired assembly and secretion of triacylglycerol-rich very low density lipoproteins: evidence that ApoC-III plays a major role in the formation of lipid precursors within the microsomal lumen. J Biol Chem. 2011;286:27769–27780.
  • Pollin TI, Damcott CM, Shen H, et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science. 2008;322:1702–1705.
  • Crosby J, Peloso GM, Auer PL, et al. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med. 2014;371:22–31.
  • Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG, et al. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med. 2014;371:32–41.
  • Arca M, Hsieh A, and Soran H, et al. The effect of volanesorsen treatment on the burden associated with familial chylomicronemia syndrome: the results of the ReFOCUS study. Expert Rev Cardiovasc Ther. 2018;16:537–546.
  • Gouni-Berthold I, Alexander VJ, and Yang Q, et al. Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2021;9:264–275.
  • Hegele RA, Joy TR, Al-Attar SA, et al. Lipodystrophies: windows on adipose biology and metabolism. J Lipid Res. 2007;48:1433–1444.
  • Alexander VJ, Xia S, Hurh E, et al. N-acetyl galactosamine-conjugated antisense drug to APOC3 mRNA, triglycerides and atherogenic lipoprotein levels. Eur Heart J. 2019;40(33):2785–2796.
  • Clifton P, Sullivan D, Baker J, et al., Abstract 12594: pharmacodynamic effect of ARO-APOC3, an investigational hepatocyte-targeted RNA interference therapeutic targeting apolipoprotein C3, in patients with hypertriglyceridemia and multifactorial chylomicronemia. Circulation. 142(Suppl_3): 12594. 2020.
  • Ng DS. Evolving ANGPTL-based lipid-lowering strategies and beyond. Curr Opin Lipidol. 2021;32(4):271–272.
  • Musunuru K, Pirruccello JP, Do R, et al. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. New Engl J Med. 2010;363(23):2220–2227.
  • Dewey FE, Gusarova V, Dunbar RL, et al. Genetic and pharmacologic inactivation of ANGPTL3 and cardiovascular disease. New Engl J Med. 2017;377(3):211–221.
  • Raal FJ, Rosenson RS, Reeskamp LF, et al. Evinacumab for homozygous familial hypercholesterolemia. New Engl J Med. 2020;383(8):711–720.
  • Markham A. Evinacumab: first approval. Drugs. 2021;81(9):1101–1105.
  • Rosenson RS, Gaudet D, Ballantyne CM, et al. A phase 2 trial of the efficacy and safety of evinacumab in patients with severe hypertriglyceridemia. Atherosclerosis. 2021;331:e293.
  • Graham MJ, Lee RG, Brandt TA, et al. Cardiovascular and metabolic effects of ANGPTL3 antisense oligonucleotides. New Engl J Med. 2017;377(3):222–232.
  • Gaudet D, Karwatowska-Prokopczuk E, Baum SJ, et al. Vupanorsen, an N-acetyl galactosamine-conjugated antisense drug to ANGPTL3 mRNA, lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia. Eur Heart J. 2020;41(40):3936–3945.
  • Pfizer Inc., Ionis Pharmaceuticals, Inc. Pfizer and ionis announce discontinuation of vupanorsen clinical development program [Internet]. New York NY and Carlsbad CA: Pfizer; January 2022. cited 2022 May 28]. Available from: https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-ionis-announce-discontinuation-vupanorsen
  • Watts GF, Schwabe C, Scott R, et al., Abstract 15751: pharmacodynamic effect of ARO-ANG3, an investigational RNA interference targeting hepatic angiopoietin-like protein 3, in patients with hypercholesterolemia. Circulation. 142(Suppl_3): 15751. 2020.
  • Rip J, van Dijk KW, Sierts JA, et al. AAV1-LPLS447X gene therapy reduces hypertriglyceridemia in apoE2 knock in mice. Biochim Biophys Acta. 2006;1761(10):1163–1168.
  • Gaudet D, Méthot J, Kastelein J. Gene therapy for lipoprotein lipase deficiency. Curr Opin Lipidol. 2012;23(4):310–320.
  • Carpentier AC, Frisch F, Labbé SM, et al. Effect of alipogene tiparvovec (AAV1-LPL S447X) on postprandial chylomicron metabolism in lipoprotein lipase-deficient patients. J Clin Endocrinol Metab. 2012;97(5):1635–1644.
  • Gaudet D, Méthot J, Déry S, et al. Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial. Gene Ther. 2013;20(4):361–369.
  • Cao J, Zhou Y, Peng H, et al. Targeting acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) with small molecule inhibitors for the treatment of metabolic diseases. J Biol Chem. 2011;286(48):41838–41851.
  • DeVita RJ, Pinto S. Current status of the research and development of diacylglycerol O -acyltransferase 1 (DGAT1) inhibitors. J Med Chem. 2013;56(24):9820–9825.
  • Schober G, Arnold M, Birtles S, et al. Diacylglycerol acyltransferase-1 inhibition enhances intestinal fatty acid oxidation and reduces energy intake in rats. J Lipid Res. 2013;54(5):1369–1384.
  • Meyers CD, Tremblay K, Amer A, et al. Effect of the DGAT1 inhibitor pradigastat on triglyceride and apoB48 levels in patients with familial chylomicronemia syndrome. Lipids Health Dis. 2015;14(1):8.
  • Meyers CD, Amer A, Majumdar T, et al. Pharmacokinetics, pharmacodynamics, safety, and tolerability of pradigastat, a novel diacylglycerol acyltransferase 1 inhibitor in overweight or obese, but otherwise healthy human subjects. J Clin Pharmacol. 2015;55(9):1031–1041.
  • Meyers C, Gaudet D, Tremblay K, et al. The DGAT1 inhibitor LCQ908 decreases triglyceride levels in patients with the familial chylomicronemia syndrome. J Clin Lipidol. 2012;6(3):266–267.
  • Wolska A, Reimund M, Remaley AT. Apolipoprotein C-II: the re-emergence of a forgotten factor. Curr Opin Lipidol. 2020;31(3):147–153.
  • Dewey FE, Gusarova V, O’Dushlaine C, et al. Inactivating variants in ANGPTL4 and risk of coronary artery disease. New Engl J Med. 2016;374(12):1123–1133.
  • Whittaker MN, Musunuru K. Therapeutic application of genome editing in dyslipidemia. Curr Opin Lipidol. 2022;33(2):133–138.