Elinzanetant: a phase III therapy for postmenopausal patients with vasomotor symptoms

References

• Monteleone P, Mascagni G, Giannini A, et al. Symptoms of menopause - global prevalence, physiology and implications. Nat Rev Endocrinol. 2018 Apr;14(4):199–215. doi: 10.1038/nrendo.2017.180
   PubMed Web of Science ®Google Scholar
• Avis NE, Crawford SL, Greendale G, et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med. 2015 Apr;175(4):531–9.
   PubMed Web of Science ®Google Scholar
• Hamoda H, Panay N, Pedder H, et al. The British menopause society & women’s health concern 2020 recommendations on hormone replacement therapy in menopausal women. Post Reprod Health. 2020 Dec;26(4):181–209.
   PubMedGoogle Scholar
• Archer DF, Schmelter T, Schaefers M, et al. A randomized, double-blind, placebo-controlled study of the lowest effective dose of drospirenone with 17beta-estradiol for moderate to severe vasomotor symptoms in postmenopausal women. Menopause. 2014 Mar;21(3):227–235.
   PubMed Web of Science ®Google Scholar
• The Hormone Therapy Position Statement of The North American Menopause Society Advisory Panel. The 2022 hormone therapy position statement of the North American menopause society. Menopause. 2022 Jul 1;29(7):767–94. doi: 10.1097/GME.0000000000002028
   PubMed Web of Science ®Google Scholar
• Depypere H, Pintiaux A, Desreux J, et al. Coping with menopausal symptoms: an internet survey of Belgian postmenopausal women. Maturitas. 2016 Aug;90:24–30.
   PubMed Web of Science ®Google Scholar
• Bluethmann SM, Murphy CC, Tiro JA, et al. Deconstructing decisions to initiate, maintain, or discontinue adjuvant endocrine therapy in breast cancer survivors: a mixed-methods study. Oncol Nurs Forum. 2017 May 1;44(3):E101–E10. doi: 10.1188/17.ONF.E101-E110
   PubMed Web of Science ®Google Scholar
• Makubate B, Donnan PT, Dewar JA, et al. Cohort study of adherence to adjuvant endocrine therapy, breast cancer recurrence and mortality. Br J Cancer. 2013 Apr 16;108(7):1515–24. doi: 10.1038/bjc.2013.116
   PubMed Web of Science ®Google Scholar
• Lan Q, Hickey M, Peate M, et al. Priorities for alleviating menopausal symptoms after cancer. Menopause. 2023 Feb 1;30(2):136–42. doi: 10.1097/GME.0000000000002108
   PubMed Web of Science ®Google Scholar
• Carpenter JS, Woods NF, Otte JL, et al. MsFLASH participants’ priorities for alleviating menopausal symptoms. Climacteric. 2015;18(6):859–66. doi: 10.3109/13697137.2015.1083003
   PubMed Web of Science ®Google Scholar
• Leon-Ferre RA, Novotny PJ, Wolfe EG, et al. Oxybutynin vs placebo for hot flashes in women with or without breast cancer: a randomized, double-blind clinical trial (ACCRU SC-1603). JNCI Cancer Spectr. 2020 Feb;4(1):kz088.
   Web of Science ®Google Scholar
• The Nonhormone Therapy Position Statement of The North American Menopause Society Advisory Panel, The 2023 nonhormone therapy position statement of the North american menopause society. Menopause. 2023 Jun 1;30(6):573–90. doi: 10.1097/GME.0000000000002200
   PubMed Web of Science ®Google Scholar
• Severini C, Improta G, Falconieri-Erspamer G, et al. The tachykinin peptide family. Pharmacol Rev. 2002 Jun;54(2):285–322.
   PubMed Web of Science ®Google Scholar
• de Roux N, Genin E, Carel JC, et al. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci USA. 2003 Sep 16;100(19):10972–10976. doi: 10.1073/pnas.1834399100
   PubMed Web of Science ®Google Scholar
• Seminara SB, Messager S, Chatzidaki EE, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003 Oct 23;349(17):1614–27. doi: 10.1056/NEJMoa035322
   PubMed Web of Science ®Google Scholar
• Topaloglu AK, Reimann F, Guclu M, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for neurokinin B in the central control of reproduction. Nat Genet. 2009 Mar;41(3):354–58. doi: 10.1038/ng.306
   PubMed Web of Science ®Google Scholar
• Oakley AE, Clifton DK, Steiner RA. Kisspeptin signaling in the brain. Endocr Rev. 2009 Oct;30(6):713–43. doi: 10.1210/er.2009-0005
   PubMed Web of Science ®Google Scholar
• Skorupskaite K, Anderson RA. Hypothalamic neurokinin signalling and its application in reproductive medicine. Pharmacol Ther. 2022 Feb;230: 107960. doi: 10.1016/j.pharmthera.2021.107960
   PubMed Web of Science ®Google Scholar
• Mileusnic D, Lee JM, Magnuson DJ, et al. Neurokinin-3 receptor distribution in rat and human brain: an immunohistochemical study. Neuroscience. 1999;89(4):1269–90. doi: 10.1016/S0306-4522(98)00349-2
   PubMed Web of Science ®Google Scholar
• Kishimoto S, Tateishi K, Kobayashi H, et al. Distribution of neurokinin A-like and neurokinin B-like immunoreactivity in human peripheral tissues. Regul Pept. 1991 Oct 29;36(2):165–71. doi: 10.1016/0167-0115(91)90054-K
   PubMedGoogle Scholar
• Rance NE, Young WS. Hypertrophy and increased gene expression of neurons containing neurokinin-B and substance-P messenger ribonucleic acids in the hypothalami of postmenopausal women. Endocrinology. 1991 May;128(5):2239–2247.
   PubMed Web of Science ®Google Scholar
• Rometo AM, Krajewski SJ, Voytko ML, et al. Hypertrophy and increased kisspeptin gene expression in the hypothalamic infundibular nucleus of postmenopausal women and ovariectomized monkeys. J Clin Endocrinol Metab. 2007 Jul;92(7):2744–50.
   PubMed Web of Science ®Google Scholar
• Rance NE, Dacks PA, Mittelman-Smith MA, et al. Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: a novel hypothesis on the mechanism of hot flushes. Front Neuroendocrinol. 2013 Aug;34(3):211–27.
   PubMed Web of Science ®Google Scholar
• Jayasena CN, Comninos AN, Stefanopoulou E, et al. Neurokinin B administration induces hot flushes in women. Sci Rep. 2015 Feb 16;5(1):8466. doi: 10.1038/srep08466
   PubMedGoogle Scholar
• Crandall CJ, Manson JE, Hohensee C, et al. Association of genetic variation in the tachykinin receptor 3 locus with hot flashes and night sweats in the Women’s health initiative study. Menopause. 2017 Mar;24(3):252–61.
   PubMed Web of Science ®Google Scholar
• Padilla SL, Johnson CW, Barker FD, et al. A neural circuit underlying the generation of hot flushes. Cell Rep. 2018 Jul 10;24(2):271–77. doi: 10.1016/j.celrep.2018.06.037
   PubMed Web of Science ®Google Scholar
• Prague JK, Roberts RE, Comninos AN, et al. Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2017 May 6;389(10081):1809–20. doi: 10.1016/S0140-6736(17)30823-1
   PubMed Web of Science ®Google Scholar
• Skorupskaite K, George JT, Veldhuis JD, et al. Neurokinin 3 receptor antagonism reveals roles for neurokinin B in the regulation of gonadotropin secretion and hot flashes in postmenopausal women. Neuroendocrinology. 2018;106(2):148–57. doi: 10.1159/000473893
   PubMed Web of Science ®Google Scholar
• Prague JK, Roberts RE, Comninos AN, et al. Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action. Menopause. 2018 Mar 12;25(8):862–869. doi: 10.1097/GME.0000000000001090
   PubMed Web of Science ®Google Scholar
• Depypere H, Lademacher C, Siddiqui E, et al. Fezolinetant in the treatment of vasomotor symptoms associated with menopause. Expert Opin Investig Drugs. 2021 Jul;30(7):681–94.
   PubMed Web of Science ®Google Scholar
• Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023 Apr 1;401(10382):1091–102. doi: 10.1016/S0140-6736(23)00085-5
   PubMed Web of Science ®Google Scholar
• Lee A. Fezolinetant: first approval. Drugs. 2023 Aug;83(12):1137–1141.
   PubMedGoogle Scholar
• Navarro VM, Bosch MA, Leon S, et al. The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction. Endocrinology. 2015 Feb;156(2):627–37.
   PubMed Web of Science ®Google Scholar
• Hrabovszky E, Borsay BA, Racz K, et al. Substance P immunoreactivity exhibits frequent colocalization with kisspeptin and neurokinin B in the human infundibular region. PLoS One. 2013;8(8):e72369. doi: 10.1371/journal.pone.0072369
   PubMed Web of Science ®Google Scholar
• Borsay BA, Skrapits K, Herczeg L, et al. Hypophysiotropic gonadotropin-releasing hormone projections are exposed to dense plexuses of kisspeptin, neurokinin B and substance p immunoreactive fibers in the human: a study on tissues from postmenopausal women. Neuroendocrinology. 2014;100(2–3):141–152. doi: 10.1159/000368362
   PubMed Web of Science ®Google Scholar
• De Muckadell OBS, Aggestrup S, Stentoft P. Flushing and plasma substance P concentration during infusion of synthetic substance P in normal man. Scand J Gastroenterol. 1986 May;21(4):498–502. doi: 10.3109/00365528609015169
   PubMed Web of Science ®Google Scholar
• Westcott EB, Segal SS. Perivascular innervation: a multiplicity of roles in vasomotor control and myoendothelial signaling. Microcirculation. 2013 Apr;20(3):217–38. doi: 10.1111/micc.12035
   PubMed Web of Science ®Google Scholar
• Ratti E, Bettica P, Alexander R, et al. Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies. J Psychopharmacol. 2013 May;27(5):424–34.
   PubMed Web of Science ®Google Scholar
• Ratti E, Carpenter DJ, Zamuner S, et al. Efficacy of vestipitant, a neurokinin-1 receptor antagonist, in primary insomnia. Sleep. 2013 Dec 1;36(12):1823–30. doi: 10.5665/sleep.3208
   PubMed Web of Science ®Google Scholar
• Catalani MP, Alvaro G, Bernasconi G, et al. Identification of novel NK1/NK3 dual antagonists for the potential treatment of schizophrenia. Bioorg Med Chem Lett. 2011 Nov 15;21(22):6899–904. doi: 10.1016/j.bmcl.2011.07.116
   PubMed Web of Science ®Google Scholar
• Ridler K, Gunn RN, Searle GE, et al. Characterising the plasma-target occupancy relationship of the neurokinin antagonist GSK1144814 with PET. J Psychopharmacol. 2014 Mar;28(3):244–53.
   PubMed Web of Science ®Google Scholar
• Te Beek ET, Hay JL, Bullman JN, et al. Pharmacokinetics and central nervous system effects of the novel dual NK1/NK3 receptor antagonist GSK1144814 in alcohol-intoxicated volunteers. Br J Clin Pharmacol. 2013 May;75(5):1328–1339.
   PubMed Web of Science ®Google Scholar
• Oakley AE, Steiner RA, Chavkin C, et al. Kappa agonists as a novel therapy for menopausal hot flashes. Menopause. 2015 Dec;22(12):1328–1334.
   PubMed Web of Science ®Google Scholar
• Fraser GL, Ramael S, Hoveyda HR, et al. The NK3 Receptor Antagonist ESN364 Suppresses Sex Hormones in men and women. J Clin Endocrinol Metab. 2016 Feb;101(2):417–26.
   PubMed Web of Science ®Google Scholar
• Skorupskaite K, George JT, Veldhuis JD, et al. Interactions between neurokinin B and kisspeptin in mediating estrogen feedback in healthy women. J Clin Endocrinol Metab. 2016 Dec;101(12):4628–36.
   PubMed Web of Science ®Google Scholar
• Skorupskaite K, George JT, Veldhuis JD, et al. Neurokinin 3 receptor antagonism decreases gonadotropin and testosterone secretion in healthy men. Clin Endocrinol (Oxf). 2017 Dec;87(6):748–56.
   PubMed Web of Science ®Google Scholar
• Anderson RA, Cormier J, Thieroff-Ekerdt R, et al. Pharmacodynamic activity of the novel neurokinin-3 receptor antagonist SJX-653 in healthy men. J Clin Endocrinol Metab. 2020 Sep 18;105(12):e4857–e65. doi: 10.1210/clinem/dgaa657
   PubMed Web of Science ®Google Scholar
• Pawsey S, Mills EG, Ballantyne E, et al. Elinzanetant (NT-814), a Neurokinin 1,3 Receptor Antagonist, Reduces Estradiol and Progesterone in Healthy Women. J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3221–e34. doi: 10.1210/clinem/dgab108
   PubMed Web of Science ®Google Scholar
• Casper RF, Yen SS, Wilkes MM. Menopausal flushes: a neuroendocrine link with pulsatile luteninizing hormone secreation. Science. 1979 Aug 24;205(4408):823–825. doi: 10.1126/science.462193
   PubMedGoogle Scholar
• Trower M, Anderson RA, Ballantyne E, et al. Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial. Menopause. 2020 Feb 17;27(5):498–505. doi: 10.1097/GME.0000000000001500
   PubMed Web of Science ®Google Scholar
• Simon JA, Anderson RA, Ballantyne E, et al. Efficacy and safety of elinzanetant, a selective neurokinin-1,3 receptor antagonist for vasomotor symptoms: a dose-finding clinical trial (SWITCH-1). Menopause. 2023 Jan 31;30(3):239–46. doi: 10.1097/GME.0000000000002138
   PubMed Web of Science ®Google Scholar
• Langer RD, Hodis HN, Lobo RA, et al. Hormone replacement therapy - where are we now? Climacteric. 2021 Feb;24(1):3–10. doi: 10.1080/13697137.2020.1851183
   PubMed Web of Science ®Google Scholar
• Nguyen PL, Alibhai SM, Basaria S, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015 May;67(5):825–836.
   PubMed Web of Science ®Google Scholar
• Sassarini J, Fox H, Ferrell W, et al. Vascular function and cardiovascular risk factors in women with severe flushing. Clin Endocrinol (Oxf). 2011 Jan;74(1):97–103.
   PubMed Web of Science ®Google Scholar
• George JT, Kakkar R, Marshall J, et al. Neurokinin B receptor antagonism in women with polycystic ovary syndrome: a randomized, placebo-controlled trial. J Clin Endocrinol Metab. 2016 Jul 26;101(11):4313–21. doi: 10.1210/jc.2016-1202
   PubMed Web of Science ®Google Scholar
• Fraser GL, Obermayer-Pietsch B, Laven J, et al. Randomized controlled trial of neurokinin 3 receptor antagonist fezolinetant for treatment of polycystic ovary syndrome. J Clin Endocrinol Metab. 2021 May 17;106(9):e3519–e32. doi: 10.1210/clinem/dgab320
   PubMed Web of Science ®Google Scholar
• Liu X, Yan D, Guo SW. Sensory nerve-derived neuropeptides accelerate the development and fibrogenesis of endometriosis. Hum Reprod. 2019 Mar 1;34(3):452–68. doi: 10.1093/humrep/dey392
   PubMed Web of Science ®Google Scholar
• Yan D, Liu X, Guo SW. Neuropeptides substance P and calcitonin gene related peptide accelerate the development and fibrogenesis of endometriosis. Sci Rep. 2019 Feb 25;9(1):2698. doi: 10.1038/s41598-019-39170-w
   PubMedGoogle Scholar
• Skorupskaite K, George JT, Veldhuis JD, et al. Neurokinin B regulates gonadotropin secretion, ovarian follicle growth, and the timing of ovulation in healthy women. J Clin Endocrinol Metab. 2018 Jan 1;103(1):95–104. doi: 10.1210/jc.2017-01306
   PubMed Web of Science ®Google Scholar