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Vonoprazan: A Review in Helicobacter pylori Infection

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Abstract

Treatment for the eradication of Helicobacter pylori infection, a leading cause of peptic ulcer disease and an important risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma, is indicated whenever infection is identified. However, treatment success rates with current guideline-recommended proton-pump inhibitor (PPI)-based regimens remain suboptimal, with one potential factor associated with treatment failure being inadequate acid suppression. Vonoprazan (Voquezna®) is a first-in-class potassium-competitive acid blocker with the potential to provide potent and sustained acid suppression. Following clinical trials conducted mainly in Asia (supported by post-marketing experience from Asia) and the phase III PHALCON-HP trial conducted in the USA and Europe, vonoprazan is now approved in the USA for use in combination with amoxicillin (dual therapy) or amoxicillin and clarithromycin (triple therapy) for the treatment of H. pylori infection in adults. The vonoprazan-based dual and triple therapy regimens were generally well tolerated in PHALCON-HP. In addition, vonoprazan has advantages including a rapid onset of action and no food effect, making vonoprazan-based dual and triple therapy regimens valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection.

Plain Language Summary

Infection with the bacterium Helicobacter pylori is a leading cause of peptic ulcer disease and has been identified as an important risk factor for gastric cancer. Current recommended treatments for H. pylori infection generally involve a combination of antibiotics together with an acid suppressant, such as a proton-pump inhibitor (PPI). However, treatment success rates with current guideline-recommended PPI-based regimens remain suboptimal. Vonoprazan (Voquezna®), from a new class of drugs known as potassium-competitive acid blockers, has the potential to provide potent and sustained acid suppression. Based on the findings of a pivotal trial (PHALCON-HP) conducted in the USA and Europe, vonoprazan is now approved in the USA for the treatment of H. pylori infection in adults when used in combination with amoxicillin, or amoxicillin and clarithromycin. Alongside the demonstrated efficacy and tolerability of the vonoprazan-based regimens, vonoprazan has a rapid onset of action and can be taken with or without food. Thus, vonoprazan-based dual and triple therapy regimens present valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection.

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References

  1. Chey WD, Leontiadis GI, Howden CW, et al. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. 2017;112(2):212–39.

    Article  PubMed  Google Scholar 

  2. Malfertheiner P, Megraud F, Rokkas T, et al. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut. 2022;71(9):1724–62.

    Article  CAS  Google Scholar 

  3. Shah S, Hubscher E, Pelletier C, et al. Helicobacter pylori infection treatment in the United States: clinical consequences and costs of eradication treatment failure. Expert Rev Gastroenterol Hepatol. 2022;16(4):341–57.

    Article  CAS  PubMed  Google Scholar 

  4. Shah SC, Iyer PG, Moss SF. AGA clinical practice update on the management of refractory Helicobacter pylori infection: expert review. Gastroenterology. 2021;160(5):1831–41.

    Article  PubMed  Google Scholar 

  5. Kim JI, Park SH, Kim JK, et al. The effects of nocturnal acid breakthrough on Helicobacter pylori eradication. Helicobacter. 2002;7(6):331–6.

    Article  PubMed  Google Scholar 

  6. Sjöstedt S, Sagar M, Lindberg G, et al. Prolonged and profound acid inhibition is crucial in Helicobacter pylori treatment with a proton pump inhibitor combined with amoxicillin. Scand J Gastroenterol. 1998;33(1):39–43.

    Article  PubMed  Google Scholar 

  7. Sugimoto M, Furuta T, Shirai N, et al. Evidence that the degree and duration of acid suppression are related to Helicobacter pylori eradication by triple therapy. Helicobacter. 2007;12(4):317–23.

    Article  CAS  PubMed  Google Scholar 

  8. Scott DR, Sachs G, Marcus EA. The role of acid inhibition in Helicobacter pylori eradication. F1000Res. 2016;5(F1000 Faculty Rev):1747.

    Article  Google Scholar 

  9. Scarpignato C, Hunt RH. Acid suppressant therapy: a step forward with potassium-competitive acid blockers. Curr Treat Options Gastro. 2021;19(1):94–132.

    Article  Google Scholar 

  10. Ohkuma K, Iida H, Inoh Y, et al. Comparison of the early effects of vonoprazan, lansoprazole and famotidine on intragastric pH: a three-way crossover study. J Clin Biochem Nutr. 2018;63(1):80–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sakurai Y, Mori Y, Okamoto H, et al. 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. 2015;42(6):719–30.

    Article  CAS  PubMed  Google Scholar 

  12. Laine L, Sharma P, Mulford DJ, et al. Pharmacodynamics and pharmacokinetics of the potassium-competitive acid blocker vonoprazan and the proton pump inhibitor lansoprazole in US subjects. Am J Gastroenterol. 2022;117(7):1158–61.

    Article  CAS  PubMed  Google Scholar 

  13. Garnock-Jones KP. Vonoprazan: first global approval. Drugs. 2015;75(4):439–43.

    Article  CAS  PubMed  Google Scholar 

  14. Chey WD, Mégraud F, Laine L, et al. Vonoprazan triple and dual therapy for Helicobacter pylori infection in the United States and Europe: randomized clinical trial. Gastroenterology. 2022;163(3):608–19.

    Article  CAS  PubMed  Google Scholar 

  15. Phathom Pharmaceuticals Inc. Voquezna Triple Pak (vonoprazan tablets; amoxicillin capsules; clarithromycin tablets) and Voquezna Dual Pak (vonoprazan tablets; amoxicillin capsules): US prescribing information. 2023. https://www.phathompharma.com/wp-content/uploads/VOQUEZNA-TRIPLE-PAK-and-VOQUEZNA-DUAL-PAK-FDA-Final-Label-3.pdf. Accessed 19 Dec 2023.

  16. Phathom Pharmaceuticals Inc. Voquezna (vonoprazan) tablets: US prescribing information. 2023. https://www.phathompharma.com/wp-content/uploads/VOQUEZNA-tablets-Prescriber-Information.pdf. Accessed 19 Dec 2023.

  17. Shin JM, Inatomi N, Munson K, et al. Characterization of a novel potassium-competitive acid blocker of the gastric H, K-ATPase, 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438). J Pharmacol Exp Ther. 2011;339(2):412–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jenkins H, Sakurai Y, Nishimura A, et al. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2015;41(7):636–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Marcus EA, Inatomi N, Nagami GT, et al. The effects of varying acidity on Helicobacter pylori growth and the bactericidal efficacy of ampicillin. Aliment Pharmacol Ther. 2012;36(10):972–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sachs G, Scott DR, Wen Y. Gastric infection by Helicobacter pylori. Curr Gastroenterol Rep. 2011;13(6):540–6.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hori Y, Imanishi A, Matsukawa J, et al. 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases. J Pharmacol Exp Ther. 2010;335(1):231–8.

    Article  CAS  PubMed  Google Scholar 

  22. Scott DR, Munson KB, Marcus EA, et al. The binding selectivity of vonoprazan (TAK-438) to the gastric H+, K+-ATPase. Aliment Pharmacol Ther. 2015;42(11–12):1315–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mulford DJ, Leifke E, Hibberd M, et al. The effect of food on the pharmacokinetics of the potassium-competitive acid blocker vonoprazan. Clin Pharmacol Drug Dev. 2022;11(2):278–84.

    Article  CAS  PubMed  Google Scholar 

  24. Yamasaki H, Kawaguchi N, Nonaka M, et al. In vitro metabolism of TAK-438, vonoprazan fumarate, a novel potassium-competitive acid blocker. Xenobiotica. 2017;47(12):1027–34.

    Article  CAS  PubMed  Google Scholar 

  25. Sakurai Y, Nishimura A, Kennedy G, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of single rising TAK-438 (vonoprazan) doses in healthy male Japanese/non-Japanese subjects. Clin Transl Gastroenterol. 2015;6(6): e94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Scarpignato C, Leifke E, Smith N, et al. A population pharmacokinetic model of vonoprazan: evaluating the effects of race, disease status, and other covariates on exposure. J Clin Pharmacol. 2022;62(6):801–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sakurai Y, Shiino M, Okamoto H, et al. Pharmacokinetics and safety of triple therapy with vonoprazan, amoxicillin, and clarithromycin or metronidazole: a phase 1, open-label, randomized, crossover study. Adv Ther. 2016;33(9):1519–35.

    Article  CAS  PubMed  Google Scholar 

  28. Ramsden D, Mulford DJ, Zhang L, et al. Novel approach to evaluate the impact of moderate and strong CYP3A inducers on vonoprazan exposure [abstract Su1203 and poster]. Gastroenterology. 2022;162(7 suppl):S-544.

    Article  Google Scholar 

  29. Jenkins H, Jenkins R, Patat A. Effect of multiple oral doses of the potent CYP3A4 inhibitor clarithromycin on the pharmacokinetics of a single oral dose of vonoprazan: a phase I, open-label, sequential design study. Clin Drug Investig. 2017;37(3):311–6.

    Article  CAS  PubMed  Google Scholar 

  30. Mulford DJ, Brudi P, Smith N, et al. A clinical drug interaction study to assess the effect of vonoprazan on the pharmacokinetics of midazolam [abstract Su1205 and poster]. Gastroenterology. 2022;162(7 suppl):S-545.

    Article  Google Scholar 

  31. Maruyama M, Tanaka N, Kubota D, et al. Vonoprazan-based regimen is more useful than PPI-based one as a first-line Helicobacter pylori eradication: a randomized controlled trial. Can J Gastroenterol Hepatol. 2017;2017(4385161):1–7.

    Article  Google Scholar 

  32. Murakami K, Sakurai Y, Shiino M, et al. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study. Gut. 2016;65(9):1439–46.

    Article  CAS  PubMed  Google Scholar 

  33. Sue S, Kuwashima H, Iwata Y, et al. The superiority of vonoprazan-based first-line triple therapy with clarithromycin: a prospective multi-center cohort study on Helicobacter pylori eradication. Intern Med. 2017;56(11):1277–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sue S, Ogushi M, Arima I, et al. Vonoprazan- vs proton-pump inhibitor-based first-line 7-day triple therapy for clarithromycin-susceptible Helicobacter pylori: a multicenter, prospective, randomized trial. Helicobacter. 2018;23(e12456):1–8.

    Google Scholar 

  35. Sue S, Shibata W, Sasaki T, et al. Randomized trial of vonoprazan-based versus proton-pump inhibitor-based third-line triple therapy with sitafloxacin for Helicobacter pylori. J Gastroenterol Hepatol. 2019;34(4):686–92.

    Article  CAS  PubMed  Google Scholar 

  36. Suzuki S, Gotoda T, Kusano C, et al. Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-line Helicobacter pylori treatment: a multicentre randomised trial in Japan. Gut. 2020;69(6):1019–26.

    Article  CAS  PubMed  Google Scholar 

  37. Hou X, Meng F, Wang J, et al. Vonoprazan non-inferior to lansoprazole in treating duodenal ulcer and eradicating Helicobacter pylori in Asian patients. J Gastroenterol Hepatol. 2022;37(7):1275–83.

    Article  CAS  PubMed  Google Scholar 

  38. Ang D, Koo SH, Chan YH, et al. Clinical trial: seven-day vonoprazan- versus 14-day proton pump inhibitor-based triple therapy for first-line Helicobacter pylori eradication. Aliment Pharmacol Ther. 2022;56(3):436–49.

    Article  CAS  PubMed  Google Scholar 

  39. Hu J, Mei H, Su NY, et al. Eradication rates of Helicobacter pylori in treatment-naive patients following 14-day vonoprazan-amoxicillin dual therapy: a multicenter randomized controlled trial in China. Helicobacter. 2023;28(4): e12970.

    Article  CAS  PubMed  Google Scholar 

  40. Hu Y, Xu X, Liu XS, et al. Fourteen-day vonoprazan and low- or high-dose amoxicillin dual therapy for eradicating Helicobacter pylori infection: a prospective, open-labeled, randomized non-inferiority clinical study. Front Immunol. 2022;13:1049908.

    Article  CAS  PubMed  Google Scholar 

  41. Yang F, Yu B, Qin L, et al. A randomized clinical study on the efficacy of vonoprazan combined with amoxicillin duo regimen for the eradication of Helicobacter pylori. Medicine (Baltimore). 2023;102(41): e35610.

    Article  CAS  PubMed  Google Scholar 

  42. Jung YS, Kim EH, Park CH. Systematic review with meta-analysis: the efficacy of vonoprazan-based triple therapy on Helicobacter pylori eradication. Aliment Pharmacol Ther. 2017;46(2):106–14.

    Article  CAS  PubMed  Google Scholar 

  43. Shinozaki S, Kobayashi Y, Osawa H, et al. Effectiveness and safety of vonoprazan versus proton pump inhibitors for second-line Helicobacter pylori eradication therapy: systematic review and meta-analysis. Digestion. 2021;102(3):319–25.

    Article  CAS  PubMed  Google Scholar 

  44. Li M, Oshima T, Horikawa T, et al. Systematic review with meta-analysis: vonoprazan, a potent acid blocker, is superior to proton-pump inhibitors for eradication of clarithromycin-resistant strains of Helicobacter pylori. Helicobacter. 2018;23(e12495):1–8.

    Google Scholar 

  45. Yang C, Li S, Huang T, et al. Effectiveness and safety of vonoprazan-based regimen for Helicobacter pylori eradication: a meta-analysis of randomized clinical trials. J Clin Pharm Ther. 2022;47(7):897–904.

    Article  CAS  PubMed  Google Scholar 

  46. Malfertheiner P, Moss SF, Daniele P, et al. Potassium-competitive acid blocker and proton pump inhibitor-based regimens for first-line Helicobacter pylori eradication: a network meta-analysis. Gastro Hep Adv. 2022;1(5):824–34.

    Article  Google Scholar 

  47. Sun Y, Yue L, Hu W. Effectiveness and safety of vonoprazan-based regimens compared with those of proton pump inhibitor (PPI)-based regimens as first-line agents for Helicobacter pylori: a meta-analysis of randomized clinical trials. Eur J Clin Pharmacol. 2023;79(2):279–88.

    Article  CAS  PubMed  Google Scholar 

  48. Sugano K, Tack J, Kuipers EJ, et al. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64(9):1353–67.

    Article  PubMed  Google Scholar 

  49. Fallone CA. The current role of vonoprazan in Helicobacter pylori treatment. Gastroenterology. 2022;163(3):572–4.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

During the peer review process the manufacturer of Voquezna® Triple Pak and Voquezna® Dual Pak was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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    Matt Shirley

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Matt Shirley is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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The manuscript was reviewed by: E. A. Argueta, Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA; R. H. Hunt, Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

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Shirley, M. Vonoprazan: A Review in Helicobacter pylori Infection. Drugs 84, 319–327 (2024). https://doi.org/10.1007/s40265-023-01991-5

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