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Review of the clinical development of fexuprazan for gastroesophageal reflux–related disease

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Abstract

Proton pump inhibitors (PPIs) are a mainstay treatment for acid peptic disorders such as gastroesophageal reflux disease (GERD). Although PPIs are considered first-line medications for acid suppression, they have notable limitations such as requiring acid-mediated activation, short half-life and duration of action, and metabolic variability. Fexuprazan is a newly developed potassium-competitive acid blocker (P-CAB), which inhibits acid generation and secretion in a competitive and reversible manner. Fexuprazan, like other P-CABs, has significantly different pharmacodynamic and pharmacokinetic properties than PPIs with potential advantages including rapid, robust, and durable acid suppression, lack of CYP2C19 metabolism, independence from food intake, and no requirement for activation into an active form. Completed clinical trials of fexuprazan have demonstrated comparable efficacy to PPIs for the healing of erosive esophagitis and relief of GERD-related esophageal symptoms without concerning safety signals. Ongoing clinical trials are evaluating fexuprazan for the prevention of NSAID-induced peptic ulcer disease, non-erosive GERD, and acute and chronic gastritis, as well as healing efficacy and maintenance of erosive esophagitis (EE). Fexuprazan is approved in South Korea for the treatment of EE and at the time of this writing is being considered for regulatory approval in several other countries. In this article, we summarize and discuss the pharmacology, efficacy, and safety of fexuprazan.

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References

  1. Katz PO, Dunbar KB, Schnoll-Sussman FH et al (2022) ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 117(1):27–56

    Article  PubMed  PubMed Central  Google Scholar 

  2. Eusebi LH, Ratnakumaran R, Yuan Y et al (2018) Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis. Gut 67(3):430–440

    Article  PubMed  Google Scholar 

  3. Wang WH, Huang JQ, Zheng GF et al (2005) Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: a meta-analysis. World J Gastroenterol 11(26):4067–4077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Khan M, Santana J, Donnellan C et al (2007) Medical treatments in the short term management of reflux oesophagitis. Cochrane Database Syst Rev (2):CD003244. Published 2007 Apr 18

  5. Chong E, Ensom MH (2003) Pharmacogenetics of the proton pump inhibitors: a systematic review. Pharmacotherapy 23(4):460–471

    Article  CAS  PubMed  Google Scholar 

  6. Richter JE, Kahrilas PJ, Johanson J et al (2001) Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial. Am J Gastroenterol 96(3):656–665

    Article  CAS  PubMed  Google Scholar 

  7. Johnson DA, Katz PO (2008) Nocturnal gastroesophageal reflux disease: issues, implications, and management strategies. Rev Gastroenterol Disord 8(2):98–108

    PubMed  Google Scholar 

  8. Peghini PL, Katz PO, Bracy NA et al (1998) Nocturnal recovery of gastric acid secretion with twice daily dosing of proton pump inhibitors. Am J Gastroenterol 93:763–767

    Article  CAS  PubMed  Google Scholar 

  9. Fouad YM, Katz PO, Castell DO (1999) Oesophageal motility defects associated with nocturnal gastro-oesophageal reflux on proton pump inhibitors. Aliment Pharmacol Ther 13:1467–1471

    Article  CAS  PubMed  Google Scholar 

  10. Fackler WK, Ours TM, Vaezi MF (2002) Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough. Gastroenterology 122(3):625–632

    Article  CAS  PubMed  Google Scholar 

  11. Hunt RH, Scarpignato C (2015) Potassium-competitive acid blockers (P-CABs): are they finally ready for prime time in acid-related disease? Clin Transl Gastroenterol 6(10):e119. Published 2015 Oct 29

  12. Abdel-Aziz Y, Metz DC, Howden CW (2021) Review article: potassium-competitive acid blockers for the treatment of acid-related disorders. Aliment Pharmacol Ther 53(7):794–809

    CAS  PubMed  Google Scholar 

  13. Ministry of Food and Drug Safety (2022) South Korean 2021 drug approval report. Government Publications. Registration number 11–1471057–000120–10

  14. Sugano K (2018) Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date. Ther Adv Gastroenterol 11:1756283X17745776. Published 2018 Jan 9

  15. Kim MS, Lee N, Lee A et al (2022) Model-based prediction of acid suppression and proposal of a new dosing regimen of fexuprazan in humans. Pharmaceuticals (Basel) 15(6):709. Published 2022 Jun 3

  16. Sunwoo J, Oh J, Moon SJ et al (2018) Safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012, a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther 48(2):206–218

    Article  CAS  PubMed  Google Scholar 

  17. Sakurai Y, Mori Y, Okamoto H et al (2015) Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects–a randomised open-label cross-over study. Aliment Pharmacol Ther 42(6):719–730

    Article  CAS  PubMed  Google Scholar 

  18. Hwang JG, Jeon I, Park SA et al (2020) Pharmacodynamics and pharmacokinetics of DWP14012 (fexuprazan) in healthy subjects with different ethnicities. Aliment Pharmacol Ther 52(11–12):1648–1657

    CAS  PubMed  Google Scholar 

  19. Lee KN, Lee OY, Chun HJ et al (2022) Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis. World J Gastroenterol 28(44):6294–6309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sung I-K, Lee OY, Choi M-G et al (2023) Randomized, double-blind, multicenter study to evaluate the efficacy and safety of dwp14012 (fexuprazan) according to the timing of dosing in patients with erosive esophagitis. Gastroenterology 164(7 Suppl):Su1311

    Google Scholar 

  21. Moon SY, Xiao Y (2023) A phase 3, non-inferiority randomized controlled trial with fexuprazan, a novel potassium-competitive acid blocker vs. esomeprazole in Chinese patients with erosive esophagitis. Gastroenterology 164(7Suppl):Su1303

    Google Scholar 

  22. Lundell L, Vieth M, Gibson F et al (2015) Systematic review: the effects of long-term proton pump inhibitor use on serum gastrin levels and gastric histology. Aliment Pharmacol Ther 42:649–663

    Article  CAS  PubMed  Google Scholar 

  23. Ashida K, Sakurai Y, Hori T et al (2016) Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. Aliment Pharmacol Ther 43(2):240–251

    Article  CAS  PubMed  Google Scholar 

  24. Cochrane Library (2023) Search | Cochrane Library. https://www.cochranelibrary.com/search. Accessed 15 Jan 2023

  25. Moon-hee C (2022) Daewoong applies for Fexuclue approval in 10 countries. BusinessKorea. http://www.businesskorea.co.kr/news/articleView.html?idxno=105999. Accessed 15 Jan 2023

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Authors and Affiliations

  1. Division of Gastroenterology, Hepatology, and Nutrition, University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 4.234, Houston, TX, 77030, USA

    Azaan Ramani & Brooks D. Cash

  2. The University of Texas at Austin, Austin, TX, USA

    Alisha Merchant

Authors
  1. Azaan Ramani
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  2. Alisha Merchant
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  3. Brooks D. Cash
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Contributions

BDC conceived the topic. BDC, AR, and AM performed the literature search and source document retrieval. AR and AM conceived and wrote the first draft of the article, and BDC provided final edits.

Corresponding author

Correspondence to Brooks D. Cash.

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The authors declare no competing interests.

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Ramani, A., Merchant, A. & Cash, B.D. Review of the clinical development of fexuprazan for gastroesophageal reflux–related disease. Eur J Clin Pharmacol 79, 1023–1029 (2023). https://doi.org/10.1007/s00228-023-03521-4

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