Filorexant Explained

Filorexant (; developmental code name MK-6096) is an orexin antagonist which was under development by Merck for the treatment of insomnia, depression, diabetic neuropathy, and migraine.[1] [2] It is a dual antagonist of the orexin OX1 and OX2 receptors.[3] [4] It has a relatively short elimination half-life of 3 to 6hours.[5] However, it dissociates slowly from the orexin receptors and may thereby have a longer duration.[6] Possibly in relation to this, filorexant shows next-day somnolence similarly to suvorexant. In phase 2 clinical trials, filorexant was found to be effective in the treatment of insomnia,[7] but was not effective in the treatment of major depressive disorder,[8] [9] [10] painful diabetic neuropathy,[11] [12] or migraine.[13], filorexant was no longer listed on Merck's online development pipeline and hence development of the drug appears to have been discontinued.[14] Development of filorexant may have been discontinued due to lack of differentiation from suvorexant (which was also developed by Merck).

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Notes and References

  1. Web site: Filorexant . AdisInsight . Springer Nature Switzerland AG .
  2. Hoyer D, Jacobson LH . Orexin in sleep, addiction and more: is the perfect insomnia drug at hand? . Neuropeptides . 47 . 6 . 477–488 . December 2013 . 24215799 . 10.1016/j.npep.2013.10.009 . 6402764 .
  3. Winrow CJ, Gotter AL, Cox CD, Tannenbaum PL, Garson SL, Doran SM, Breslin MJ, Schreier JD, Fox SV, Harrell CM, Stevens J, Reiss DR, Cui D, Coleman PJ, Renger JJ . 6 . Pharmacological characterization of MK-6096 - a dual orexin receptor antagonist for insomnia . Neuropharmacology . 62 . 2 . 978–987 . February 2012 . 22019562 . 10.1016/j.neuropharm.2011.10.003 . 35304627 .
  4. Peroutka SJ . Clinical trials update. 2013: year in review . Headache . 54 . 1 . 189–194 . January 2014 . 24400767 . 10.1111/head.12267 . 28141555 .
  5. Hoyer D, Jacobson LH . Orexin Receptor Antagonists . Current Sleep Medicine Reports . 13 November 2017 . 3 . 4 . 342–353 . 2198-6401 . 10.1007/s40675-017-0099-7 . 11343/282828 . 80067706 . free .
  6. Jacobson LH, Hoyer D, de Lecea L . Hypocretins (orexins): The ultimate translational neuropeptides . Journal of Internal Medicine . 291 . 5 . 533–556 . May 2022 . 35043499 . 10.1111/joim.13406 . 248119793 .
  7. Connor KM, Mahoney E, Jackson S, Hutzelmann J, Zhao X, Jia N, Snyder E, Snavely D, Michelson D, Roth T, Herring WJ . 6 . A Phase II Dose-Ranging Study Evaluating the Efficacy and Safety of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Primary Insomnia . The International Journal of Neuropsychopharmacology . 19 . 8 . pyw022 . August 2016 . 26979830 . 5006195 . 10.1093/ijnp/pyw022 .
  8. Summers CH, Yaeger JD, Staton CD, Arendt DH, Summers TR . Orexin/hypocretin receptor modulation of anxiolytic and antidepressive responses during social stress and decision-making: Potential for therapy . Brain Research . 1731 . 146085 . March 2020 . 30590027 . 6591110 . 10.1016/j.brainres.2018.12.036 .
  9. Han Y, Yuan K, Zheng Y, Lu L . Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders . Neuroscience Bulletin . 36 . 4 . 432–448 . April 2020 . 31782044 . 7142186 . 10.1007/s12264-019-00447-9 .
  10. Connor KM, Ceesay P, Hutzelmann J, Snavely D, Krystal AD, Trivedi MH, Thase M, Lines C, Herring WJ, Michelson D . 6 . Phase II Proof-of-Concept Trial of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Major Depressive Disorder . The International Journal of Neuropsychopharmacology . 20 . 8 . 613–618 . August 2017 . 28582570 . 5570043 . 10.1093/ijnp/pyx033 .
  11. Book: Steiner MA, Winrow CJ . Insomnia and beyond - Exploring the therapeutic potential of orexin receptor antagonists. 11 November 2014. Frontiers E-books. 978-2-88919-330-1. 3–.
  12. Joseph Herring W, Ge JY, Jackson S, Assaid C, Connor KM, Michelson D . Orexin Receptor Antagonism in Painful Diabetic Neuropathy: A Phase 2 Trial With Filorexant . The Clinical Journal of Pain . 34 . 1 . 37–43 . January 2018 . 28448426 . 10.1097/AJP.0000000000000503 . 23060776 .
  13. Chabi A, Zhang Y, Jackson S, Cady R, Lines C, Herring WJ, Connor KM, Michelson D . 6 . Randomized controlled trial of the orexin receptor antagonist filorexant for migraine prophylaxis . Cephalalgia . 35 . 5 . 379–388 . April 2015 . 25106663 . 10.1177/0333102414544979 . 20872932 .
  14. Web site: Merck Pipeline. 2015-05-14. Merck. 2015.

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