Naldemedine: First Global Approval

Abstract

Naldemedine (Symproic®) is an orally active µ-opioid receptor antagonist being developed by Shionogi & Co., Ltd. that has been approved in the USA and Japan for the treatment of opioid-induced constipation. The drug inhibits peripheral µ-opioid receptors such as those present in the gastrointestinal tract and has minimal or no effect on central opioid activity. This article summarizes the milestones in the development of naldemedine leading to its first global approval in the USA for the treatment of opioid-induced constipation in patients with chronic non-cancer pain.

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References

  1. 1.

    Camilleri M, Drossman DA, Becker G, et al. Emerging treatments in neurogastroenterology: a multidisciplinary working group consensus statement on opioid-induced constipation. Neurogastroenterol Motil. 2014;26(10):1386–95.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Shionogi Inc. FDA approves Symproic® (naldemedine) once-daily tablets C-II for the treatment of opioid-induced constipation in adults with chronic non-cancer pain [media release]; 2017.

  3. 3.

    Shionogi & Co. Ltd. Symproic® (naldemedine) approved for the treatment of opioid-induced constipation in Japan [media release]; 2017.

  4. 4.

    Shionogi Inc. SYMPROIC® (Naldemedine): US Prescribing Information; 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208854s000lbl.pdf. Accessed 6 April 2017.

  5. 5.

    Shionogi & Co. Ltd. Shionogi and Purdue Pharma establish alliance for joint U.S. commercialization of naldemedine [media release]. 19 December 2016.

  6. 6.

    Webster LR, Yamada T, Arjona Ferreira JC. A phase 2b, randomized, double-blind placebo-controlled study to evaluate the efficacy and safety of naldemedine for the treatment of opioid-induced constipation in patients with chronic noncancer pain. Pain Med. 2017;. doi:10.1093/pm/pnw325.

    PubMed Central  Google Scholar 

  7. 7.

    Kanemasa T, Koike K, Arai T, et al. Effects of naldemedine: a peripherally acting mu-opioid receptor antagonist in rat models of opioid-induced constipation [abstract no. 1322]. Am J Gastroenterol. 2015;110(Suppl. 1):S578.

    Google Scholar 

  8. 8.

    Migoya E, Fukumura K, Yamada T, et al. Effect of naldemedine, a peripherally acting mu-opioid receptor antagonist on QT interval [abstract no. 426]. J Pain. 2016;17(4 Suppl. 1):S81.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Hale M, Wild J, Reddy J, et al. Efficacy and safety of naldemedine for the treatment of opioid-induced constipation in subjects with chronic non-cancer pain receiving opioid therapy: results from two phase 3 clinical trials [abstract no. OP338]. United Eur Gastroenterol J. 2016;4(5 Suppl):A132.

    Google Scholar 

  10. 10.

    Wild J, Reddy J, et al. Efficacy and safety of naldemedine for the treatment of opioid-induced constipation in subjects with chronic non-cancer pain receiving opioid therapy: results from two phase 3 clinical trials [abstract no. 598]. Gastroenterology. 2016;150(4 Suppl. 1):S121–2.

    Google Scholar 

  11. 11.

    Arjona Ferreira JC, Reddy J, Yamada T, et al. A phase 3, randomized, double-blind, placebo-controlled study of naldemedine for the treatment of opioid-induced constipation (OIC) in patients with chronic noncancer pain receiving opioid therapy [abstract no. 192]. Pain Med. 2016;17(2):422.

    Google Scholar 

  12. 12.

    Wild J, Hale M, Reddy J, et al. Onset of action of naldemedine in the treatment of opioid-induced constipation in patients with chronic non-cancer pain: results from two randomized, placebo-controlled phase 3 trials [abstract no. 522]. Am J Gastroenterol. 2016;111(Suppl. 1):S236–7.

    Google Scholar 

  13. 13.

    Webster L, Nalamachu S, Yamada T, et al. Long-term safety and efficacy of naldemedine for the treatment of opioid-induced constipation in subjects with chronic non-cancer pain receiving opioid therapy. Results from a 52-week phase 3 clinical trial [abstract no. 7]. Postgrad Med. 2016;128(Suppl. 2):5.

    Google Scholar 

  14. 14.

    Harada T, Katakami N, Murata T, et al. Phase 3 study to evaluate the efficacy and safety of naldemedine for the treatment of opioid-induced constipation (OIC) in cancer patients [abstract no. 10016]. J Clin Oncol. 2016;34(Suppl.).

  15. 15.

    Murata T, Katakami N, Harada T, et al. Treatment of opioid-induced constipation with naldemedine in patients with cancer: onset of action in a randomized phase 3 trial [abstract no. 1466P]. Ann Oncol. 2016;27(Suppl. 6).

  16. 16.

    Webster L, Nagata T, Yamada T, et al. A phase 2a, randomized, double-blind, placebo-controlled, single ascending-dose study to evaluate the safety and efficacy of naldemedine in patients with chronic noncancer pain and opioid-induced bowel dysfunction [abstract no. 479]. J Pain. 2016;17(4 Suppl.):S94.

    Google Scholar 

  17. 17.

    Boku N, Katakami N, Fujita S, et al. A phase II randomized, double-blind, placebo-controlled study to evaluate naldemedine for the treatment of opioid-induced constipation (OIC) in patients with cancer pain [abstract no. 9594 ]. J Clin Oncol. 2015;33(15 Suppl. 1).

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. A. Markham is a contracted employee of Adis, Springer SBM.

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Correspondence to Anthony Markham.

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This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

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Markham, A. Naldemedine: First Global Approval. Drugs 77, 923–927 (2017). https://doi.org/10.1007/s40265-017-0750-0

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Keywords

  • Placebo Recipient
  • Naltrexone
  • Moxifloxacin
  • Oxycodone
  • Spontaneous Bowel Movement