代谢相关脂肪性肝病药物研发进展

摘要/Abstract

摘要： 非酒精性脂肪性肝病(NAFLD)/非酒精性脂肪性肝炎(NASH)目前仍未有批准治疗药物,随着流行率的日益增长和高度未满足的医疗需求,相关药物研发的迫切性与日剧增。在过去的几十年中,NASH新药研发经历诸多波折,但在2023年取得了令人瞩目的进步,本文将主要介绍在这一年取得的最新进展。

邢翔宇, 牛俊奇. 代谢相关脂肪性肝病药物研发进展[J]. 肝脏, 2024, 29(1): 5-9.

[1] Estes C, Anstee QM, Arias-Loste MT, et al. Modeling NAFLD disease burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030[J]. J Hepatol, 2018, 69(4): 896-904.
[2] Burra P, Becchetti C, Germani G. NAFLD and liver transplantation: Disease burden, current management and future challenges[J]. JHEP Rep, 2020, 2(6): 100192.
[3] Hallsworth K, Adams LA. Lifestyle modification in NAFLD/NASH: Facts and figures[J]. JHEP Rep, 2019, 1(6): 468-479. DOI: 10.1016/j.jhepr.2019.10.008.
[4] Xu XH, Poulsen KL, Wu LJ, et al. Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)[J]. Signal Transduct Target Ther, 2022, 7: 287. DOI: 10.1038/s41392-022-01119-3.
[5] Yabut JM, Drucker DJ. Glucagon-like peptide-1 receptor-based therapeutics for metabolic liver disease[J]. Endocr Rev, 2023, 44(1): 14-32.
[6] Mantovani A, Petracca G, Beatrice G, et al. Glucagon-like peptide-1 receptor agonists for treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: An updated meta-analysis of randomized controlled trials[J]. Metabolites, 2021, 11(2): 73.
[7] Park MJ, Kim H, Kim MG, et al. Comparison of glucagon-like peptide-1 receptor agonists and thiazolidinediones on treating nonalcoholic fatty liver disease: A network meta-analysis[J]. Clin Mol Hepatol, 2023, 29(3): 693-704.
[8] Stephen AH, Shaheen T, SUSCHAK JJ, et al. Pemvidutide-induced liver fat reduction in subjects with nonalcoholic fatty liver disease correlate with improvements in noninvasive markers of inflammation and fibrosis: results of a 24-week multicenter, randomized, doubleblind, placebo-controlled trial[EB/OL]. AASLD 2023 Late-Breaking Abstracts,2023. https://www.aasld.org/sites/default/files/2023-11/SLD-625%20Late%20Breaking%20Abstract.pdf
[9] Jastreboff AM, Kaplan LM, Hartman ML. Triple-hormone-receptor agonist retatrutide for obesity. reply[J]. N Engl J Med, 2023, 389(17): 1629-1630.
[10] Benjamin JB, Joshua CW, Jonathan O, et al. ORAL LPCN 1148 improves sarcopenia and hepatic encephalopathy in patients with cirrhosis[EB/OL]. AASLD 2023 Late-BreakingAbstracts,2023. https://www.aasld.org/sites/default/files/2023-11/SLD-625%20Late%20Breaking%20Abstract.pdf.
[11] Stephen AH, Juan PF, Kathryn JL, et al. Safety and efficacy of efruxifermin in combination with a GLP-1 receptor agonist (GLP-1RA) in patients with NASH/MASH and T2D: a randomized, placebo-controlled study (cohort D)[EB/OL]. AASLD 2023 Late-Breaking Abstracts,2023. https://www.aasld.org/sites/default/files/2023-11/SLD-625%20Late%20Breaking%20Abstract.pdf.
[12] 常洪楷, 赵冬. 成纤维细胞生长因子21在代谢性疾病中的研究进展[J]. 温州医科大学学报, 2023, 53(12): 1015-1022.
[13] Loomba R, Sanyal AJ, Kowdley KV, et al. Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH. N Engl J Med. 2023;389(11):998-1008.
[14] Harrison SA, Frias JP, Neff G, et al. Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): A multicentre, randomised, double-blind, placebo-controlled, phase 2b trial[J]. Lancet Gastroenterol Hepatol, 2023, 8(12): 1080-1093. DOI: 10.1016/S2468-1253(23)00272-8.
[15] Stephen AH, Guy WN, Kathryn JL, et al. Efruxifermin in compensated cirrhosis due to nash/mash: results from a randomized, double-blind, placebo-controlled, phase 2b trial (symmetry)[EB/OL]. AASLD 2023 Late-Breaking Abstracts,2023. https://www.aasld.org/sites/default/files/2023-11/SLD-625%20Late%20Breaking%20Abstract.pdf.
[16] Loomba R, et al. AASLD 2023. Poster #2403-C
[17] Rinella ME, Lieu HD, Kowdley KV, et al. A randomized, double-blind, placebo-controlled trial of Aldafermin in patients with nonalcoholic steatohepatitis and compensated cirrhosis[J]. Hepatology, 2023.
[18] Staels B, Butruille L, Francque S. Treating NASH by targeting peroxisome proliferator-activated receptors. J Hepatol. 2023;79(5):1302-1316.
[19] Francque SM, Bedossa P, Ratziu V, et al. A randomized, controlled trial of the pan-PPAR agonist lanifibranor in NASH[J]. N Engl J Med, 2021, 385(17): 1547-1558.
[20] Diana B, Srilaxmi K, Eddison G, et al. Lanifibranor reverses insulin resistance and improves glucose and lipid metabolism in patients with type 2 diabetes (T2D) and metabolic dysfunctionassociated steatotic liver disease (MASLD)[EB/OL]. AASLD 2023 Late-Breaking Abstracts,2023. https://www.aasld.org/sites/default/files/2023-11/SLD-625%20Late%20Breaking%20Abstract.pdf.
[21] Li LM, Song Y, Shi YQ, et al. Thyroid hormone receptor-β agonists in NAFLD therapy: Possibilities and challenges[J]. J Clin Endocrinol Metab, 2023, 108(7): 1602-1613.
[22] Zhou J, Tripathi M, Ho JP, et al. Thyroid hormone decreases hepatic steatosis, inflammation, and fibrosis in a dietary mouse model of nonalcoholic steatohepatitis[J]. Thyroid, 2022, 32(6): 725-738.
[23] Karim G, Bansal MB. Resmetirom: An orally administered, smallmolecule, liver-directed, β-selective THR agonist for the treatment of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis[J]. touchREV Endocrinol, 2023, 19(1): 60-70.
[24] Harrison SA, Taub R, Neff GW, et al. Resmetirom for nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled phase 3 trial[J]. Nat Med, 2023, 29(11): 2919-2928.
[25] Rohit L, Manuel R, Muhammad Y, et al. The novel thyroid hormone receptor beta agonist VK2809 significantly reduces liver fat in patients with nash and fibrosis, results from the primary endpoint of the ongoing phase 2b voyage study[EB/OL]. AASLD 2023 Late-Breaking Abstracts,2023. https://www.aasld.org/sites/default/files/2023-11/SLD-625%20Late%20Breaking%20Abstract.pdf.
[26] Terns Pharmaceuticals. Terns achieves primary endpoint and all secondary endpoints in phase 2a duet trial of THR-β agonist TERN-501 in NASH[EB/OL]. https://ir.ternspharma.com/news-releases/news-release-details/terns-achieves-primary-endpoint-and-all-secondary-endpoints.
[27] Ratziu V, et al. AASLD 2023. Poster #2473-C

代谢相关脂肪性肝病药物研发进展

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