New drugs for pulmonary hypertension

European Respiratory Monograph

Volumn 57, Issue , 2012, Pages 233-246

  O'Connell, Caroline ^a   O'Callaghan, Dermot S ^a   Gaine, Sean ^a  

^a MATER MISERICORDIAE UNIVERSITY HOSPITAL   (Ireland)

Author keywords

Endothelial progenitor cell; Endothelin antagonist; Guanylate cyclase stimulator; Prostacyclin receptor agonist; Rho kinase; Tyrosine kinase inhibitors

Indexed keywords

EID: 84865578402     PISSN: 1025448X     EISSN: 20756674     Source Type: Book Series    
DOI: 10.1183/1025448x.10020211     Document Type: Article

References (92)

1. Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122: 156-163.
2. D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115: 343-349.
3. O'Callaghan DS, Savale L, Montani D, et al. Treatment of pulmonary arterial hypertension with targeted therapies. Nat Rev Cardiol 2011; 8: 526-538.
4. Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993; 328: 1732-1739.
5. O'Callaghan DS, Humbert M, Simonneau G. Treatment strategies for severe PAH: the present and the future. In: Malley J, ed. Pulmonary Hypertension: the Present and the Future. Beijing, People's Medical Publishing House USA, 2011; pp. 265-276.
6. Kummer O, Haschke M, Hammann F, et al. Comparison of the dissolution and pharmacokinetic profiles of two galenical formulations of the endothelin receptor antagonist macitentan. Eur J Pharm Sci 2009; 38: 384-388.
7. Sidharta PN, van Giersbergen PL, Halabi A, et al. Macitentan: entry-into-humans study with a new endothelin receptor antagonist. Eur J Clin Pharmacol 2011; 67: 977-984.
8. Raja SG. Macitentan, a tissue-targeting endothelin receptor antagonist for the potential oral treatment of pulmonary arterial hypertension and idiopathic pulmonary fibrosis. Curr Opin Investig Drugs 2010; 11: 1066-1073.
9. Actelion. Study of ACT 064992 on morbidity and mortality in patients with symptomatic pulmonary arterial hypertension. http://clinicaltrials.gov/ct2/show/NCT00660179?term5SERAPHIN&rank522008 Date last accessed: March 2012. Date last updated: April 30, 2012.
10. Christman BW, McPherson CD, Newman JH, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 1992; 327: 70-75.
11. Barst RJ, Rubin LJ, McGoon MD, et al. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994; 121: 409-415.
12. Gomberg-Maitland M, Olschewski H. Prostacyclin therapies for the treatment of pulmonary artery hypertension. Eur Respir J 2008; 31: 891-901.
13. US Food and Drug Administration. Veletri (epoprostenol sodium) injection. www.fda.gov/Safety/MedWatch/ SafetyInformation/ucm250257.htm?utm_source5fdaSearch&utm_medium5website&utm_term5veletri&utm_ content51 Date last accessed: March 2012. Date last updated: April 12, 2011.
14. GlaxoSmithKline. Study of a new thermo stable formulation of epoprostenol sodium to treat pulmonary arterial hypertension (PAH). www.clinicaltrials.gov/ct2/show/NCT01462565?term5veletri&rank512011 Date last accessed: April 2012. Date last updated: May 24, 2012.
15. Tapson VF, Torres F, Kermeen F, et al. Results of the FREEDOM-C study: a pivotal study of oral treprostinil used adjunctively with an ERA and/or PDE5-inhibitor for the treatment of PAH. Am J Respir Crit Care Med 2009; 179: A1040.
16. United Therapeutics. A 16-week, international, multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of oral UT-15C sustained release tablets in subjects with pulmonary arterial hypertension (FREEDOM-C2). www.clinicaltrials.gov/ct2/show/NCT00887978?term5FREEDOM-C2&rank512011 Date last accessed: April 2012. Date last updated: May 5, 2011.
17. United Therapeutics. UT-15C treprostinil diethanolamine sustained release tablets (oral treprostinil). www. unither.com/oral-treprostinil-for-pah Date last accessed: 2011.
18. United Therapeutics. FREEDOM-M: oral treprostinil as monotherapy for the treatment of pulmonary arterial hypertension (PAH). www.clinicaltrials.gov/ct2/show/NCT00325403?term5FREEDOM-M&rank512012 Date last accessed: April 2012. Date last updated: April, 18: 2011.
19. Voswinckel R, Reichenberger F, Gall H, et al. Metered dose inhaler delivery of treprostinil for the treatment of pulmonary hypertension. Pulm Pharmacol Ther 2009; 22: 50-56.
20. Gomberg-Maitland M, Olschewski H. Prostacyclin therapies for the treatment of pulmonary arterial hypertension. Eur Respir J 2008; 31: 891-901.
21. Kuwano K, Hashino A, Asaki T, et al. 2-[4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy]-N-(methylsulfonyl)acetamide (NS-304), an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther 2007; 322: 1181-1188.
22. McLaughlin VV. Looking to the future: a new decade of pulmonary arterial hypertension therapy. Eur Respir Rev 2011; 20: 262-269.
23. Simonneau G, Torbicki A, Hoeper MM, et al. Selexipag, an oral, selective IP receptor agonist for the treatment of pulmonary arterial hypertension. Eur Respir J 2012; [Epub ahead of print DOI: 10.1183/09031936.00137511].
24. Actelion. ACT-293987 in pulmonary arterial hypertension. www.clinicaltrials.gov/ct2/show/ NCT01106014?term5GRIPHON&rank512012 Date last accessed: April 2012. Date last updated: May 24, 2012.
25. Archer SL, Michelakis ED. Phosphodiesterase type 5 inhibitors for pulmonary arterial hypertension. N Engl J Med 2009; 361: 1864-1871.
26. Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353: 2148-2157.
27. Galie N, Brundage BH, Ghofrani HA, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation 2009; 119: 2894-2903.
28. Montani D, Chaumais MC, Savale L, et al. Phosphodiesterase type 5 inhibitors in pulmonary arterial hypertension. Adv Ther 2009; 26: 813-825.
29. Jing ZC, Jiang X, Wu BX, et al. Vardenafil treatment for patients with pulmonary arterial hypertension: a multicentre, open-label study. Heart 2009; 95: 1531-1536.
30. Jing ZC, Yu ZX, Shen JY, et al. Vardenafil in pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med 2011; 183: 1723-1729.
31. Evgenov OV, Pacher P, Schmidt PM, et al. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov 2006; 5: 755-768.
32. Grimminger F, Weimann G, Frey R, et al. First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. Eur Respir J 2009; 33: 785-792.
33. Ghofrani HA, Hoeper MM, Halank M, et al. Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Eur Respir J 2010; 36: 792-799.
34. Bayer. A study to evaluate efficacy and safety of oral BAY63-2521 in patients with pulmonary arterial hypertension (PAH). http://clinicaltrials.gov/ct2/show/NCT00810693?term5BAY63-2521&rank512011 Date last accessed: April 2012. Date last updated: June 4, 2012.
35. Bayer. A study to evaluate efficacy and safety of oral BAY63-2521 in patients with CTEPH. (CHEST-1). www. clinicaltrials.gov/ct2/show/NCT00855465?term5CHEST%2C+riociguat&rank522012 Date last accessed: April 2012. Date last updated: June 11, 2012.
36. Ghofrani HA, Osterloh IH, Grimminger F. Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat Rev Drug Discov 2006; 5: 689-702.
37. Bayer. Evaluation of the pharmacodynamic effect of the combination of sildenafil and riociguat on blood pressure and other safety parameters (PATENT PLUS). www.clinicaltrials.gov/ct2/show/NCT01179334?term5PATENTPLUS& rank51 Date last accessed: April 2012. Date last updated: June 8, 2012.
38. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002; 106: 1477-1482.
39. Perros F, Montani D, Dorfmuller P, et al. Platelet-derived growth factor expression and function in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 2008; 178: 81-88.
40. Ghofrani HA, Morrell NW, Hoeper MM, et al. Imatinib in pulmonary arterial hypertension patients with inadequate response to established therapy. Am J Respir Crit Care Med 2010; 182: 1171-1177.
41. Hoeper M, Barst R, Bourge R, et al. Imatinib improves exercise capacity and hemodynamics at 24 weeks as add-on therapy in symptomatic pulmonary arterial hypertension patients: the IMPRES study. Chest 2011; 140: 1045A.
42. Kim TD, le Coutre P, Schwarz M, et al. Clinical cardiac safety profile of nilotinib. Haematologica 2012; 97: 883-889.
43. Novartis. Efficacy, safety, tolerability and pharmacokinetics (PK) of nilotinib (AMN107) in pulmonary arterial hypertension. http://clinicaltrials.gov/ct2/show/NCT01179737?term5Nilotinib+pulmonary&rank512010 Date last accessed: April 2012. Date last updated: December 8, 2011.
44. Moreno-Vinasco L, Gomberg-Maitland M, Maitland ML, et al. Genomic assessment of a multikinase inhibitor, sorafenib, in a rodent model of pulmonary hypertension. Physiol Genomics 2008; 33: 278-291.
45. Gomberg-Maitland M, Maitland ML, Barst RJ, et al. A dosing/cross-development study of the multikinase inhibitor sorafenib in patients with pulmonary arterial hypertension. Clin Pharmacol Ther 2010; 87: 303-310.
46. Humbert M, Simonneau G, Dinh-Xuan AT. Whistleblowers. Eur Respir J 2011; 38: 510-511.
47. Montani D, Bergot E, Gunther S, et al. Pulmonary arterial hypertension in patients treated by dasatinib. Circulation 2012; 125: 2128-2137.
48. Dempsie Y, MacLean MR. Pulmonary hypertension: therapeutic targets within the serotonin system. Br J Pharmacol 2008; 155: 455-462.
49. Herve P, Launay JM, Scrobohaci ML, et al. Increased plasma serotonin in primary pulmonary hypertension. Am J Med 1995; 99: 249-254.
50. Launay JM, Herve P, Peoc'h K, et al. Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension. Nat Med 2002; 8: 1129-1135.
51. Eddahibi S, Humbert M, Fadel E, et al. Serotonin transporter overexpression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J Clin Invest 2001; 108: 1141-1150.
52. Eddahibi S, Chaouat A, Morrell N, et al. Polymorphism of the serotonin transporter gene and pulmonary hypertension in chronic obstructive pulmonary disease. Circulation 2003; 108: 1839-1844.
53. Zhai FG, Zhang XH, Wang HL. Fluoxetine protects against monocrotaline-induced pulmonary arterial hypertension: potential roles of induction of apoptosis and upregulation of Kv1.5 channels in rats. Clin Exp Pharmacol Physiol 2009; 36: 850-856.
54. Shah SJ, Gomberg-Maitland M, Thenappan T, et al. Selective serotonin reuptake inhibitors and the incidence and outcome of pulmonary hypertension. Chest 2009; 136: 694-700.
55. Dumitrascu R, Kulcke C, Konigshoff M, et al. Terguride ameliorates monocrotaline-induced pulmonary hypertension in rats. Eur Respir J 2011; 37: 1104-1118.
56. Hamidi SA, Prabhakar S, Said SI. Enhancement of pulmonary vascular remodelling and inflammatory genes with VIP gene deletion. Eur Respir J 2008; 31: 135-139.
57. Said SI, Hamidi SA, Dickman KG, et al. Moderate pulmonary arterial hypertension in male mice lacking the vasoactive intestinal peptide gene. Circulation 2007; 115: 1260-1268.
58. Petkov V, Mosgoeller W, Ziesche R, et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest 2003; 111: 1339-1346.
59. Leuchte HH, Baezner C, Baumgartner RA, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J 2008; 32: 1289-1294.
60. Kip1. J Biol Chem 1999; 274: 21926-21931.
61. Zhao L, Sebkhi A, Ali O, et al. Simvastatin and sildenafil combine to attenuate pulmonary hypertension. Eur Respir J 2009; 34: 948-957.
62. Kao PN. Simvastatin treatment of pulmonary hypertension: an observational case series. Chest 2005; 127: 1446-1452.
63. Kawut SM, Bagiella E, Lederer DJ, et al. Randomized clinical trial of aspirin and simvastatin for pulmonary arterial hypertension: ASA-STAT. Circulation 2011; 123: 2985-2993.
64. Wilkins MR, Ali O, Bradlow W, et al. Simvastatin as a treatment for pulmonary hypertension trial. Am J Respir Crit Care Med 2010; 181: 1106-1113.
65. Saadjian A, Philip-Joet F, Paganelli F, et al. Long-term effects of cicletanine on secondary pulmonary hypertension. J Cardiovasc Pharmacol 1998; 31: 364-371.
66. US NIH ClinicalTrials. gov. Study of Cicletanine for Pulmonary Arterial Hypertension (PAH). http://clinicaltrials. gov/ct2/show/NCT00832507 Date last updated: August 2011. Date last accessed: April 2012.
67. Guilluy C, Eddahibi S, Agard C, et al. RhoA and Rho kinase activation in human pulmonary hypertension: role of 5-HT signaling. Am J Respir Crit Care Med 2009; 179: 1151-1158.
68. Oka M, Fagan KA, Jones PL, et al. Therapeutic potential of RhoA/Rho kinase inhibitors in pulmonary hypertension. Br J Pharmacol 2008; 155: 444-454.
69. Abe K, Shimokawa H, Morikawa K, et al. Long-term treatment with a Rho-kinase inhibitor improves monocrotaline-induced fatal pulmonary hypertension in rats. Circ Res 2004; 94: 385-393.
70. Fukumoto Y, Matoba T, Ito A, et al. Acute vasodilator effects of a Rho-kinase inhibitor, fasudil, in patients with severe pulmonary hypertension. Heart 2005; 91: 391-392.
71. Fujita H, Fukumoto Y, Saji K, et al. Acute vasodilator effects of inhaled fasudil, a specific Rho-kinase inhibitor, in patients with pulmonary arterial hypertension. Heart Vessels 2010; 25: 144-149.
72. Ishikura K, Yamada N, Ito M, et al. Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension. Circ J 2006; 70: 174-178.
73. Pacaud P, Loirand G. Rho kinase inhibitors for pulmonary hypertension: waiting for clinical evidence. Eur Respir J 2010; 36: 709-711.
74. Hardavella GF, Dionellis GS, Kantza CG, et al. Latest therapeutic novelties and patents in pulmonary hypertension. Recent Pat Cardiovasc Drug Discov 2011; 6: 55-60.
75. Dahal BK, Kosanovic D, Pamarthi PK, et al. Therapeutic efficacy of azaindole-1 in experimental pulmonary hypertension. Eur Respir J 2010; 36: 808-818.
76. Kakishita M, Nishikimi T, Okano Y, et al. Increased plasma levels of adrenomedullin in patients with pulmonary hypertension. Clin Sci (Lond) 1999; 96: 33-39.
77. Nagaya N, Kyotani S, Uematsu M, et al. Effects of adrenomedullin inhalation on hemodynamics and exercise capacity in patients with idiopathic pulmonary arterial hypertension. Circulation 2004; 109: 351-356.
78. McMurtry MS, Bonnet S, Wu X, et al. Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res 2004; 95: 830-840.
79. Dewachter L, Dewachter C, Naeije R. New therapies for pulmonary arterial hypertension: an update on current bench to bedside translation. Expert Opin Investig Drugs 2010; 19: 469-488.
80. University of Alberta, Imperial College London. Dichloroacetate (DCA) for the treatment of pulmonary arterial hypertension. www.clinicaltrials.gov/ct2/show/NCT01083524?term5dichloroacetate&rank51 Date last accessed: April 2012. Date last updated: November 3, 2011.
81. Dewachter L, Adnot S, Fadel E, et al. Angiopoietin/Tie2 pathway influences smooth muscle hyperplasia in idiopathic pulmonary hypertension. Am J Respir Crit Care Med 2006; 174: 1025-1033.
82. Ferreira AJ, Shenoy V, Yamazato Y, et al. Evidence for angiotensin-converting enzyme 2 as a therapeutic target for the prevention of pulmonary hypertension. Am J Respir Crit Care Med 2009; 179: 1048-1054.
83. Zhao YD, Courtman DW, Deng Y, et al. Rescue of monocrotaline-induced pulmonary arterial hypertension using bone marrow-derived endothelial-like progenitor cells: efficacy of combined cell and eNOS gene therapy in established disease. Circ Res 2005; 96: 442-450.
84. Launay JM, Herve P, Callebert J, et al. Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension. Blood 2012; 119: 1772-1780.
85. Gambaryan N, Perros F, Montani D, et al. Targeting of c-kit+ haematopoietic progenitor cells prevents hypoxic pulmonary hypertension. Eur Respir J 2011; 37: 1392-1399.
86. Wang XX, Zhang FR, Shang YP, et al. Transplantation of autologous endothelial progenitor cells may be beneficial in patients with idiopathic pulmonary arterial hypertension: a pilot randomized controlled trial. J Am Coll Cardiol 2007; 49: 1566-1571.
87. Northern Therapeutics, St Michael's Hospital, Davis MB. Pulmonary hypertension: assessment of cell therapy (PHACeT). http://clinicaltrials.gov/ct2/show/NCT00469027?term5PHACeT&rank512010 Date last accessed: April 2012. Date last updated: June 6, 2011.
88. O'Callaghan DS, Gaine SP. Combination therapy and new types of agents for pulmonary arterial hypertension. Clin Chest Med 2007; 28: 169-185.
89. Rubin LJ, Galie N. Pulmonary arterial hypertension: a look to the future. J Am Coll Cardiol 2004; 43: 89S-90S.
90. Galiè N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2009; 34: 1219-1263.
91. Peacock A, Keogh A, Humbert M. Endpoints in pulmonary arterial hypertension: the role of clinical worsening. Curr Opin Pulm Med 2010; 16: Suppl. 1, S1-S9.
92. US NIH ClinicalTrials. gov. A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH) (AMBITION). http://clinicaltrials.gov/ct2/show/NCT01178073 Date last updated: December 2011. Date last accessed: April 2011.