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Review

Emerging drugs for the treatment of idiopathic pulmonary fibrosis: 2020 phase II clinical trials

ORCID Icon, &
Pages 93-101 | Received 01 Feb 2021, Accepted 13 May 2021, Published online: 24 May 2021

References

  • Sgalla G, Biffi A, Richeldi L. Idiopathic pulmonary fibrosis: diagnosis, epidemiology and natural history. Respirology. 2016;21(3):427–437.
  • Richeldi L, Du Bois RM, Raghu G, et al., Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 370(22): 2071–2082. 2014.
  • King TE, Bradford WZ, Castro-Bernardini S, et al., A Phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 370(22): 2083–2092. 2014.
  • Ruffenach G, Hong J, Vaillancourt M, et al. Pulmonary hypertension secondary to pulmonary fibrosis: clinical data, histopathology and molecular insights. Respir Res. 2020;21(1):1–14.
  • Zisman DA, Schwarz M, Anstrom KJ, et al. A controlled trial of sildenafil in advanced idiopathic pulmonary fibrosis. N Engl J Med. 2010 Aug 12;363(7):620-628.
  • Kolb M, Raghu G, Wells AU, et al. Nintedanib plus sildenafil in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2018Nov 1;379(18):1722-1731.
  • Behr J, Nathan SD, Wuyts WA, et al. Efficacy and safety of sildenafil added to pirfenidone in patients with advanced idiopathic pulmonary fibrosis and risk of pulmonary hypertension: a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med. 2020;9(1):85–95.
  • Wallace WAH, Ramage EA, Lamb D, et al. A type 2 (Th2-like) pattern of immune response predominates in the pulmonary interstitium of patients with cryptogenic fibrosing alveolitis (CFA). Clin Exp Immunol. 1995 Sep;101(3):436-441.
  • Belperio JA, Dy M, Burdick MD, et al. Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol. 2002;27(4):419–427.
  • Hancock A, Armstrong L, Gama R, et al. Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung. Am J Respir Cell Mol Biol. 1998;18(1):60–65.
  • Jakubzick C, Choi ES, Joshi BH, et al. Therapeutic attenuation of pulmonary fibrosis via targeting of IL-4- and IL-13-responsive cells. J Immunol. 2003;171(5):2684–2693.
  • Kolodsick JE, Toews GB, Jakubzick C, et al. Protection from fluorescein isothiocyanate-induced fibrosis in IL-13-deficient, but Not IL-4-deficient, mice results from impaired collagen synthesis by fibroblasts. J Immunol. 2004;172(7):4068–4076.
  • Maher TM, Costabel U, Glassberg MK, et al. Phase 2 trial to assess lebrikizumab in patients with idiopathic pulmonary fibrosis. Eur Respir J. 2020 Feb 4;57(2):1902442.
  • Pilling D, Gomer RH. The development of serum amyloid p as a possible therapeutic. Front Immunol. 2018;9. DOI:10.3389/fimmu.2018.02328
  • Pilling D, Buckley CD, Salmon M, et al. Inhibition of Fibrocyte Differentiation by Serum Amyloid P. J Immunol. 2003;171(10):5537–5546.
  • Pilling D, Roife D, Wang M, et al. Reduction of Bleomycin-Induced Pulmonary Fibrosis by Serum Amyloid P. J Immunol. 2007;179(6):4035–4044.
  • Dillingh MR, Van Den Blink B, Moerland M, et al. Recombinant human serum amyloid P in healthy volunteers and patients with pulmonary fibrosis. Pulm Pharmacol Ther. 2013;26(6):672–676.
  • Raghu G, Van Den Blink B, Hamblin MJ, et al., Effect of recombinant human pentraxin 2 vs placebo on change in forced vital capacity in patients with idiopathic pulmonary fibrosis a randomized clinical trial. J Am Med Assoc. 319(22): 2299. 2018.
  • Raghu G, Van Den Blink B, Hamblin MJ, et al. Long-term treatment with recombinant human pentraxin 2 protein in patients with idiopathic pulmonary fibrosis: an open-label extension study. Lancet Respir Med. 2019;7(8):657–664.
  • Yung YC, Stoddard NC, Chun J. LPA receptor signaling: pharmacology, physiology, and pathophysiology. J Lipid Res. 2014 Jul;55(7):1192-214.
  • Tager AM, LaCamera P, Shea BS, et al. The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak. Nat Med. 2008Jan;14(1):45-54.
  • Oikonomou N, Mouratis MA, Tzouvelekis A, et al. Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Cell Mol Biol. 2012;47(5):566–574.
  • Maher TM, Van Der Aar EM, Van De Steen O, et al., Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial. Lancet Respir Med. 6(8): 627–635. 2018.
  • Swaney JS, Chapman C, Correa LD, et al. A novel, orally active LPA 1 receptor antagonist inhibits lung fibrosis in the mouse bleomycin model. Br J Pharmacol. 2010;160(7):1699–1713.
  • Palmer SM, Snyder L, Todd JL, et al. Randomized, double-blind, placebo-controlled, Phase 2 trial of BMS-986020, a lysophosphatidic acid receptor antagonist for the treatment of idiopathic pulmonary fibrosis. Chest. 2018;154(5):1061–1069.
  • Murphy B, Sum C-S, Wang T, et al. LPA1 antagonist BMS-986278 for idiopathic pulmonary fibrosis: preclinical pharmacological in vitro and in vivo evaluation. 2019.
  • Tirucherai G, Yu D, Revankar R, et al. BMS-986278, a lysophosphatidic acid 1 (LPA1) receptor antagonist, in healthy participants: a single/multiple ascending dose (SAD/MAD) phase 1 study. 2019.
  • Lipson KE, Wong C, Teng Y, et al. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair. 2012;5(S1). DOI:10.1186/1755-1536-5-S1-S24
  • Pan L-H, Yamauchi K, Uzuki M, et al. Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF. Eur Respir J. 2001 Jun;17(6):1220.
  • Allen JT, Knight RA, Bloor CA, et al. Enhanced insulin-like growth factor binding protein–related protein 2 (connective tissue growth factor) expression in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Cell Mol Biol. 1999;21(6):693–700.
  • Wang X, Wu G, Gou L, et al. A novel single-chain-Fv antibody against connective tissue growth factor attenuates bleomycin-induced pulmonary fibrosis in mice. Respirology. 2011;16(3):500–507.
  • Raghu G, Scholand MB, De Andrade J, et al. FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in idiopathic pulmonary fibrosis. Eur Respir J. 2016;47(5):1481–1491.
  • Richeldi L, Fernández Pérez ER, Costabel U, et al., Pamrevlumab, an anti-connective tissue growth factor therapy, for idiopathic pulmonary fibrosis (PRAISE): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 8(1): 25–33. 2020.
  • Saniere L, Marsais F, Jagerschmidt C, et al. Characterization of GLPG1205 in mouse fibrosis models: a potent and selective antagonist of GPR84 for treatment of idiopathic pulmonary fibrosis. 2019.
  • Demedts M, Behr J, Buhl R, et al. High-dose acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2005;353(21):2229–2242.
  • Raghu G, Anstrom KJ, King TE, et al. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N Engl J Med. 2012;366(21):1968–1977.
  • Martinez FJ, De Andrade JA, Anstrom KJ, et al. Randomized trial of acetylcysteine in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2093-101.
  • Behr J, Bendstrup E, Crestani B, et al. Safety and tolerability of acetylcysteine and pirfenidone combination therapy in idiopathic pulmonary fibrosis: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. 2016;4(6):445–453.
  • Oldham JM, Ma SF, Martinez FJ, et al. TOLLIP, MUC5B, and the response to N-acetylcysteine among individuals with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2015;192(12):1475–1482.
  • Homma S, Azuma A, Taniguchi H, et al. Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis. Respirology. 2012;17(3):467–477.
  • Sakamoto S, Kataoka K, Kondo Y, et al. Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial. Eur Respir J [Internet]. 2020; Available from:. . : https://erj.ersjournals.com/content/early/2020/07/16/13993003.00348–2020
  • François A, Gombault A, Villeret B, et al. B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis. J Autoimmun. 2015 Jan;56:1–11.
  • Xue J, Kass DJ, Bon J, et al. Plasma B lymphocyte stimulator and B cell differentiation in idiopathic pulmonary fibrosis patients. J Immunol. 2013;191(5):2089–2095.
  • Donahoe M, Valentine VG, Chien N, et al. Autoantibody-targeted treatments for acute exacerbations of idiopathic pulmonary fibrosis. Maher TM, editor. PLoS One. 2015 Jun;10(6):e0127771.
  • Garneau-Tsodikova S, Thannickal V. Protein kinase inhibitors in the treatment of pulmonary fibrosis. Curr Med Chem. 2008;15(25):2632–2640.
  • Van Der Velden JL, Alcorn JF, Chapman DG, et al. Airway epithelial specific deletion of Jun-N-terminal kinase 1 attenuates pulmonary fibrosis in two independent mouse models. PLoS One. 2020;15(1):e0226904.
  • Schafer PH, Ye Y, Chen P, et al. Pharmacodynamic and pharmacokinetic assessment of the C-Jun N-terminal kinase (JNK) inhibitor CC-930 in a phase 2 sequential ascending dose study in idiopathic pulmonary fibrosis (IPF). Am J Respir Crit Care Med. 2013.
  • Greenberg S, Horan G, Bennett B, et al. Late breaking abstract - evaluation of the JNK inhibitor, CC-90001, in a phase 1b pulmonary fibrosis trial. 2017:187:A5708 .
  • HSP. 47siRNA targeting to myofibroblasts attenuates bleomycin-induced pulmonary fibrosis. Eur Respir J. 2012'40: 4533.
  • Zabludoff S, Liu Y, Liu J, et al. Late breaking abstract - ND-L02-s0201 treatment leads to efficacy in preclinical IPF models. 2017.
  • MacKinnon AC, Gibbons MA, Farnworth SL, et al. Regulation of transforming growth factor-β1-driven lung fibrosis by galectin-3. Am J Respir Crit Care Med. 2012;185(5):537–546.
  • TD139, A Novel Inhaled Galectin-3 Inhibitor for The Treatment of Idiopathic Pulmonary Fibrosis (IPF). Results from the first in (IPF) patients study. QJM An Int J Med. 2016'195:A7560.
  • Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Sep;28(7):451-95.
  • Izumo T, Kondo M, Nagai A. Effects of a leukotriene B4 receptor antagonist on bleomycin-induced pulmonary fibrosis. Eur Respir J. 2009;34(6):1444–1451.
  • Bascom R, Hitz K, Dimmock AEF, et al. Description of protocol to evaluate MN-001’S (tipelukast) efficacy, safety and tolerability in subjects with idiopathic pulmonary fibrosis. 2020.
  • Huang X, Kawakatsu H. The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for 4 5 6 regulating pulmonary inflammation and fibrosis. Cel. 1999;Feb 5;96(3):319-328.
  • Decaris M, Schaub J, Chen C, et al. Dual α V β 6/α V β 1 Inhibitor PLN-74809 reduces fibrogenesis in ex vivo and in vivo models of IPF. 2019.
  • Gorina E, Decaris M, Turner S, et al. PLN-74809, A dual α V β 6/α V β 1, oral, selective integrin inhibitor, is well tolerated and reduces lung TGF-β activity in healthy volunteers. 2020.
  • Lefebvre E, Coulie B, Jurek M, et al. INTEGRIS-IPF: a 12-week, Phase 2a study evaluating the safety, tolerability and pharmacokinetics of PLN-74809 in participants with IPF. 2020.
  • Parker JM, Glaspole IN, Lancaster LH, et al. A phase 2 randomized controlled study of tralokinumab in subjects with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2018;197(1):94–103.
  • Ni K, Liu M, Zheng J, et al. PD-1/PD-L1 pathway mediates the alleviation of pulmonary fibrosis by human mesenchymal stem cells in humanized mice. Am J Respir Cell Mol Biol. 2018;58(6):684–695.
  • Raghu G, Richeldi L, Crestani B, et al. SAR156597 in idiopathic pulmonary fibrosis: a phase 2 placebo-controlled study (DRI11772). Eur Respir J. 2018;52(6):1801130.

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