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Characteristics of the Novel Potassium-Competitive Acid Blocker Vonoprazan Fumarate (TAK-438)

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Abstract

Proton pump inhibitors (PPIs) are widely prescribed as first-line therapy for the treatment of acid-related diseases, such as peptic ulcers and gastro-esophageal reflux disease, and for the eradication of Helicobacter pylori. However, the therapeutic efficacy of conventional PPIs is considered limited because: (1) they are unstable under acidic conditions and require an enteric-coated formulation in clinical use; (2) they show high interindividual variability in pharmacokinetics due to genetic polymorphisms of cytochrome P450 (CYP) 2C19 metabolism; (3) they have a relatively slow onset of pharmacological action and may require several doses to achieve optimal acid suppression and symptom relief; and (4) they often do not provide stable suppression of gastric acid secretion over 24 h. Vonoprazan fumarate (TAK-438, hereinafter referred to as “vonoprazan”) is a new potassium-competitive acid blocker (P-CAB) developed to resolve the above limitations of conventional PPIs. Various physicochemical data have shown that vonoprazan has a high solubility and stability over a broad pH range in aqueous conditions. In addition, vonoprazan has a more potent and longer-lasting acid suppression effect than the conventional PPI, lansoprazole. Preclinical pharmacokinetic studies have shown that vonoprazan is accumulated and retained in the stomach for more than 24 h, even after it is eliminated from the plasma. From these findings, we propose that vonoprazan, which possesses a novel mode of action, can improve on the outcomes seen with conventional PPI-based treatments for acid-related diseases.

Funding

This review project, including the publication of this article, was funded by Takeda Pharmaceutical Company Limited.

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Acknowledgments

Sponsorship and article processing charges for this study were funded by Takeda Pharmaceutical Company Limited.

We express our thanks to Mr. Masayuki Aboshi and Mr. Shigeki Okita of the Medical Science Liaison Group, Medical Affairs Department, Japan Research Center, Takeda Pharmaceutical Company Limited, and Mr. Francois Jones of Quintiles Transnational Japan Co., Ltd. for their support in drafting this article. We also thank the Medical Science Liaison Group, Medical Affairs Department, Japan Research Center, Takeda Pharmaceutical Company Limited for providing scientific advice. Dr. Keisuke Ishida of SunFlare Co., Ltd. provided medical writing support, which was funded by Takeda Pharmaceutical Company Limited. Mr. Yoshitaka Sato of Saikou, provided medical illustration service, which was funded by Takeda Pharmaceutical Company Limited.

This article was originally published in Japanese in the journal Progress in Medicine. Permission to translate and republish the article in English was granted by the publisher of Progress in Medicine. Kazuyoshi Otake, Yuichi Sakurai, Haruyuki Nishida, Hideo Fukui, Yoshihiko Tagawa, Hitomi Yamasaki, Masatoshi Karashima, Keiichi Otsuka, Nobuhiro Inatomi. Vonoprazan Fumarate (TAK-438). A New Potassium-Competitive Acid Blocker (P-CAB) with a Novel Mode of Action—physicochemical Properties, Non-Clinical Data, and a Proposed Mode of Action. Progress in Medicine 2014:34(12):2183–2194. Translation of the article from Japanese to English was funded by Takeda Pharmaceuticals USA, Inc. and performed by a native Japanese-speaking translator specialized in the life sciences. The translation was conducted according to rigid ISO 9001:2008 and EN 15038:2006 certified quality assurance processes. This article is a translation of the original Japanese article to English with updates.

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Disclosures

Kazuyoshi Otake, Yuuichi Sakurai, Haruyuki Nishida, Hideo Fukui, Yoshihiko Tagawa, Hitomi Yamasaki, Masatoshi Karashima, Keiichi Otsuka and Nobuhiro Inatomi are employees of Takeda Pharmaceutical Company Limited, and there are no other applicable matters regarding conflicts of interest.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Global Medical Affairs Japan Department, Takeda Pharmaceutical Co., Ltd., Tokyo, Japan

    Kazuyoshi Otake

  2. Clinical Science, Takeda Development Center Japan, Takeda Pharmaceutical Co., Ltd., Osaka, Japan

    Yuuichi Sakurai

  3. Medicinal Chemistry Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan

    Haruyuki Nishida

  4. Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan

    Hideo Fukui

  5. Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan

    Yoshihiko Tagawa & Hitomi Yamasaki

  6. Analytical Development Laboratories, CMC Center, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan

    Masatoshi Karashima

  7. Analytical Development Laboratories, CMC Center, Takeda Pharmaceutical Co., Ltd., Osaka, Japan

    Keiichi Otsuka

  8. Extra Value Generation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Co., Ltd., Kanagawa, Japan

    Nobuhiro Inatomi

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  1. Kazuyoshi Otake
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Otake, K., Sakurai, Y., Nishida, H. et al. Characteristics of the Novel Potassium-Competitive Acid Blocker Vonoprazan Fumarate (TAK-438). Adv Ther 33, 1140–1157 (2016). https://doi.org/10.1007/s12325-016-0345-2

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