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Drug Discovery in Japan pp 127–146Cite as

Pranlukast (Onon)

An Anti-asthmatic Drug Realized by Intensive Investment in the Arachidonic Acidcascade

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Abstract

Pranlukast hydrate (Onon) was the world’s first cysteinyl leukotriene (CysLT) receptor antagonist and was developed by Ono Pharmaceutical. The innovation of pranlukast is summarized by its provision of an oral agent with high efficacy against bronchial asthma, and its novel mechanism of action. The case of pranlukast development has the following implications. The first is the importance of the contribution of the underlying scientific knowledge to the development of a drug with a novel mechanism of action, particularly at the conceptualization stage of the project. In the case of pranlukast, the discovery of leukotrienes was the contributing factor. The second is the importance of accumulating drug development experience. Such development of expertise allowed Ono Pharmaceutical to discover such a promising compound ahead of other companies located around the globe that were also in competition to develop an LT antagonist. Pranlukast was the first antagonist of CysLT receptors to be developed and became a highly successful drug in Japan with annual sales of tens of billions of yen. However, the third LT antagonist, montelukast (Singulair), has recorded far greater sales than pranlukast globally. These facts provide two additional insights into a market competition of the pharmaceutical industry. The first is related to patent protection and the subsequent entries into the market. The second is the importance of complementary assets in market competition.

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Notes

  1. 1.

    Leukotrienes include LTA4 (leukotriene A4), LTB4, LTC4, LTD4, LTE4, and LTF4. Among them, LTC4, LTD4, LTE4 are called cysteinyl leukotrienes (CysLTs) because they have cysteine residues in their structures (Kanaoka 2011).

  2. 2.

    Pharmaceutical Interview Form: Onon Capsules 112.5 mg (revised December 2011, 8th edn), p. 1, 62.

  3. 3.

    Pharmaceutical Interview Form: Onon Dry Syrup 10% (revised January 2012, 8th edn), p. 1, 70.

  4. 4.

    Pharmaceutical Interview Form: Onon Capsules 112.5 mg (revised December 2011, 8th edn), p. 1.

  5. 5.

    Ono Pharmaceutical “Supplementary Explanation Materials for Financial Results (Fiscal Year 2007, Consolidated and Non-consolidated).”

  6. 6.

    “The total number of patients” in the survey refers to those who were continually receiving medical care at the date of the survey, including those who had not received medical treatment at a medical facility at the date of the survey.

  7. 7.

    The prevalence rate is the ratio of those who responded “with asthma symptoms within the past 12 months” in the questionnaire.

  8. 8.

    WHO Fact sheet on asthma, http://www.who.int/en/news-room/fact-sheets/detail/asthma, (accessed 31 July 2018).

  9. 9.

    Pharmaceutical Interview Form: Onon Capsules 112.5 mg (revised December 2011, 8th edn), p. 18.

  10. 10.

    This section is based on Murota (1988, pp. 41–43) and Tada (1988, p. 1).

  11. 11.

    Sakamoto and Sato (1983), Hayashi (1983), and Tada (1988) have detailed the history of PG research.

  12. 12.

    Kurzrok and Lieb speculated that the seminal fluid contained acetylcholine, which was already known to cause contractions of the myometrium and did not indicate the presence of a new agent. Therefore, the honor of the discovery of prostaglandin does not belong to them.

  13. 13.

    Nikkei Daily Morning Edition, 7 February 1984, p. 14.

  14. 14.

    Hayashi (1983, Chap. 7) and Tada (1988, Chap. 1) describe the history of the discovery of leukotrienes. This section refers to these articles.

  15. 15.

    AA-861, discovered by Takeda Pharmaceutical, was one of the biosynthetic inhibitors that emerged early in the development competition. However, it was not commercialized because of poor pharmacokinetics in humans. In the United States, a 5-lipoxygenase inhibitor zileuton (Zyflo) was commercialized in 1997. Zileuton is hepatotoxic and requires periodic liver function tests (Abiru 2001).

  16. 16.

    Toda and Arai (1987) and Arai (1988) were detailed about the development approach.

  17. 17.

    RS-001 was the compound whose antagonistic activity was found by random screening, and ONO-1078 (pranlukast) was synthesized and developed from the same compound. Note that “RS” of RS-001 came from random screening.

  18. 18.

    Pharmaceutical Interview Form: Onon Capsules 112.5 mg (revised December 2011, 8th edn), p. 1.

  19. 19.

    Nikkei Daily Morning Edition, 29 September 1984, p. 16.

  20. 20.

    The Compiled Works of E. J. Corey, http://www.ejcorey.org/corey/publications/publications.php, (accessed 24 February 2014).

  21. 21.

    Pharmaceutical Interview Form: Azeptin Tablets 0.5 mg, Azeptin Tablets 1 mg, Azeptin Granules 0.2% (revised February 2012, 8th edn), p. 10.

  22. 22.

    Pharmaceutical Interview Form: Vega Tablets 100 mg/200 mg (revised January 2010, 3rd edn), p. 9.

  23. 23.

    Pharmaceutical Interview Form: Domenan Tablets 100 mg, Domenan Tablets 200 mg (revised April 2011, 3rd edn), p. 8.

  24. 24.

    Pharmaceutical Interview Form: Onon Capsules 112.5 mg (revised December 2011, 8th edn), p. 11.

  25. 25.

    Ono Pharmaceutical “Notice of Amendment to Forecast of Full-Term Results for the Year Ended March 31, 2008”, 8 November 2007.

  26. 26.

    Upjohn was a company that had been engaged in research since the beginning in the PG field. This may been because of the tight connection between Bergström, who accomplished isolation and identification of PGs, and the company. For such fundamental work, various boosts, including funds were indispensable, and the very person who took care of this was Dr. Weisblatt of Upjohn, an old friend of Bergström (Sakamoto and Sato 1983, p. 4).

  27. 27.

    In the interview, it was speculated that Merck’s clinical development slowed down, because of some trouble with the clinical compound under development, forcing the company to change to montelukast.

  28. 28.

    Pharmaceutical Interview Form: Singulair Tablets 5 mg, Singulair Tablets 10 mg, Singulair Tablets 5 mg, Singulair Fine Granules 4 mg (revised in April 2014, 29th edn), p. 1, 68.

  29. 29.

    Pharmaceutical Interview Form: Acolate Tablets 20 mg (revised in November 2011, 8th edn), p. 1.

  30. 30.

    Corporate financial data were obtained from Nikkei NEEDS-FinancialQUEST.

  31. 31.

    Nikkei Business Daily, 1 April 1993, p. 15.

  32. 32.

    IMS R&D Focus Drug News, 17 May 1999.

  33. 33.

    Nikkei Business Daily, 8 November 2000, p. 10.

  34. 34.

    Nikkei Business Daily, 28 August 2002, p. 11.

References

  • Abiru, T. (2001). LT receptor antagonists. In S. Murota & S. Yamamoto (Eds.), New Development of Prostaglandin Research (Vol. 38, pp. 202–206). Tokyo: Tokyo Kagaku Dojin (in Japanese).

    Google Scholar 

  • Arai, Y. (1988). Leukotriene. In S. Yamamoto & S. Murota (Eds.), Prostaglandin (Vol. 7, pp. 143–157). Tokyo: Tokyo Kagaku Dojin. (in Japanese).

    Google Scholar 

  • Ebisawa, M. (2011). Management of infantile asthma in JPGL 2008. Japanese Journal of Pediatric Allergy and Clinical Immunology, 25(4), 700–704. (in Japanese).

    Article  Google Scholar 

  • Fukui, Y., Hizawa, N., Takahashi, D., Maeda, Y., Kobayashi, M., Nasuhara, Y., et al. (2008). Efficacy of leukotriene receptor antagonists in asthma treatment and analysis of background factors evaluated by a questionnaire survey among physicians. Annals of The Japanese Respiratory Society, 46(12), 972–980. (in Japanese).

    Google Scholar 

  • Fukutomi, Y., Nakamura, H., Kobayashi, F., Taniguchi, M., Konno, S., Nishimura, M., et al. (2010). Nationwide cross-sectional population-based study on the prevalences of asthma and asthma symptoms among Japanese adults. International Archives of Allergy and Immunology, 152(3), 280–287.

    Article  Google Scholar 

  • Hayashi, M. (1983). New bioactive substances: Prostaglandins and related substances. Tokyo: Kaimeisha. (in Japanese).

    Google Scholar 

  • Kanaoka, Y. (2011). Cysteinyl leukotriene receptor. Seikagaku, 83(7), 609–614. (in Japanese).

    Google Scholar 

  • Miyamoto, A., Takishima, T., Makino, S., Shida, T., & Nakashima, M. (1993a). Effect of ONO-1078, a selective antagonist to leukotriene C4, D4, and E4 receptors on treatment of bronchial asthma in adults. Journal of Clinical and Experimental Medicine, 164(4), 225–247. (in Japanese).

    Google Scholar 

  • Miyamoto, A., Takishima, T., Makino, S., Shida, T., Nakashima, M., & Hanaoka, K. (1993b). Effect of ONO-1078, a Leukotriene C4, D4, and E4 receptor antagonist on treatment of bronchial asthma in adults. Journal of Clinical Therapeutics & Medicines, 9(1), 71–107. (in Japanese).

    Google Scholar 

  • Mouri, T. (2008). The development and the history of ONON. Japanese Journal of National Medical Services, 62(4), 245–246. (in Japanese).

    Google Scholar 

  • Murota, S. (1988). Advances in prostaglandin research. Clinician, 35(367), 40–51. (in Japanese).

    Google Scholar 

  • Nagase, T. (2009). 3. Topics of asthma-related mediators. Nihon Naika Gakkai Zasshi, 98(12), 3013–3018. (in Japanese).

    Article  Google Scholar 

  • Noyori, R. (2011). Facts are the enemy of truth. Tokyo: Nihon Keizai Shinbunsha. (in Japanese).

    Google Scholar 

  • Obata, T. (2001). Research and development of leukotriene receptor antagonist ONON. Farumashia, 37(1), 16. (in Japanese).

    Google Scholar 

  • Sakamoto, S., & Sato, K. (1983). Prostaglandin story. Tokyo: Kodansha. (in Japanese).

    Google Scholar 

  • Sala, A., Proschak, E., Steinhilber, D., & Rovati, G. E. (2018). Two-pronged approach to anti-inflammatory therapy through the T modulation of the arachidonic acid cascade. Biochemical Pharmacology, 158, 161–173.

    Article  Google Scholar 

  • Tada, M. (1988). Prostaglandins. Kyoto: Kagaku Dojin. (in Japanese).

    Google Scholar 

  • Tamura, G. (2003). Category and class of leukotriene receptor antagonists. In M. Adachi (Ed.), A complete guide to leukotriene receptor antagonists (pp. 44–50). Tokyo: SENTA IGAKU-SHA (in Japanese).

    Google Scholar 

  • Tamura, G. (2004). Special feature leukotrienes and anti-leukotrienes: Introduction. Allergy and Immunity, 11(11), 9. (in Japanese).

    Google Scholar 

  • Tamura, G. (2005). Recent trends and future issues of asthma mortality in Japan. Allergology International, 54(2), 223–227.

    Article  Google Scholar 

  • Tamura, G., Inoue, H., Chihara, J., & Takishima, T. (2000). Population-based open-label clinical effectiveness assessment of the cysteinyl leukotriene receptor antagonist pranlukast. Allergology International, 49(3), 189–194.

    Article  Google Scholar 

  • Toda, M., & Arai, Y. (1987). Biological activities of leukotriene derivatives and development of leukotriene antagonist. Journal of Synthetic Organic Chemistry, 45(2), 136–150. (in Japanese).

    Article  Google Scholar 

  • Tsuboshima, M., Matsumoto, K., Arai, Y., Wakatsuka, H., & Kawasaki, A. (1992). Prostaglandins: Synthetic and pharmacological studies and development. Yakugaku Zasshi, 112(7), 447–469. (in Japanese).

    Article  Google Scholar 

  • Yoshihara, S. (2009). Treatment strategies using leukotriene receptor antagonists. Allergy and Immunity, 16(6), 791–793. (in Japanese).

    Google Scholar 

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Authors and Affiliations

  1. Kobe University, Kobe, Japan

    Kenta Nakamura

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  1. Kenta Nakamura
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Editors and Affiliations

  1. Department of Economics, Tokyo Keizai University, Kokubunji, Tokyo, Japan

    Sadao Nagaoka

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Nakamura, K. (2019). Pranlukast (Onon). In: Nagaoka, S. (eds) Drug Discovery in Japan. Springer, Singapore. https://doi.org/10.1007/978-981-13-8906-1_8

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