Development of evocalcet for unmet needs among calcimimetic agents

References

• Isakova T, Wahl P, Vargas GS, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011;79(12):1370–1378.
   PubMed Web of Science ®Google Scholar
• Tentori F, Wang M, Bieber BA, et al. Recent changes in therapeutic approaches and association with outcomes among patients with secondary hyperparathyroidism on chronic hemodialysis: the DOPPS study. Clin J Am Soc Nephrol. 2015;10(1):98–109.
   PubMed Web of Science ®Google Scholar
• Kidney Disease: Improving Global Outcomes CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2009;(113):S1–130. doi(113):S1-130.
   Google Scholar
• Fukagawa M, Yokoyama K, Koiwa F, et al. Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder. Ther Apher Dial. 2013;17(3):247-288.
   Web of Science ®Google Scholar
• Komaba H, Kakuta T, Fukagawa M. Management of secondary hyperparathyroidism: how and why? Clin Exp Nephrol. 2017;21(Suppl 1):37–45.
   PubMed Web of Science ®Google Scholar
• Kifor O, Moore FD Jr., Wang P, et al. Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab. 1996;81(4):1598–1606.
   PubMed Web of Science ®Google Scholar
• Fukuda N, Tanaka H, Tominaga Y, et al. Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. J Clin Invest. 1993;92(3):1436–1443.
   PubMed Web of Science ®Google Scholar
• Gogusev J, Duchambon P, Hory B, et al. Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int. 1997 Jan;51(1):328–336.
   PubMed Web of Science ®Google Scholar
• Tokumoto M, Tsuruya K, Fukuda K, et al. Reduced p21, p27 and vitamin D receptor in the nodular hyperplasia in patients with advanced secondary hyperparathyroidism. Kidney Int. 2002 Oct;62(4):1196–1207.
   PubMed Web of Science ®Google Scholar
• Komaba H, Goto S, Fujii H, et al. Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. Kidney Int. 2010;77(3):232–238.
   PubMed Web of Science ®Google Scholar
• Block GA, Klassen PS, Lazarus JM, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol. 2004;15(8):2208-2218.
   Web of Science ®Google Scholar
• Tentori F, Blayney MJ, Albert JM, et al. Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2008 Sep;52(3):519–530.
   PubMed Web of Science ®Google Scholar
• Taniguchi M, Fukagawa M, Fujii N, et al. Serum phosphate and calcium should be primarily and consistently controlled in prevalent hemodialysis patients. Ther Apher Dial. 2013;17(2):221-228.
   Web of Science ®Google Scholar
• Komaba H, Taniguchi M, Wada A, et al. Parathyroidectomy and survival among Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int. 2015;88(2):350–359.
   PubMed Web of Science ®Google Scholar
• Kestenbaum B, Andress DL, Schwartz SM, et al. Survival following parathyroidectomy among United States dialysis patients. Kidney Int. 2004;66(5):2010–2016.
   PubMed Web of Science ®Google Scholar
• Costa-Hong V, Jorgetti V, Gowdak LHW, et al. Parathyroidectomy reduces cardiovascular events and mortality in renal hyperparathyroidism. Surgery. 2007;142(5):699–703.
   PubMed Web of Science ®Google Scholar
• Investigators ET, Chertow GM, Block GA, et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367(26):2482–2494.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Sterling LR, Parfrey PS, et al. Assessing the treatment effect in a randomized controlled trial with extensive non-adherence: the EVOLVE trial. Pharm Stat. 2015;14(3):242–251.
   PubMed Web of Science ®Google Scholar
• Akizawa T, Kurita N, Mizobuchi M, et al. PTH-dependence of the effectiveness of cinacalcet in hemodialysis patients with secondary hyperparathyroidism. Sci Rep. 2016 Apr;6:19612.
   PubMed Web of Science ®Google Scholar
• Hruska KA, Teitelbaum SL. Renal osteodystrophy. N Engl J Med. 1995;333(3):166–174.
   PubMed Web of Science ®Google Scholar
• Rudser KD, de Boer IH, Dooley A, et al. Fracture risk after parathyroidectomy among chronic hemodialysis patients. J Am Soc Nephrol. 2007 Aug;18(8):2401–2407.
   PubMed Web of Science ®Google Scholar
• Moe SM, Chertow GM, Parfrey PS, et al. Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: the evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial. Circulation. 2015 Jul;132(1):27–39.
   PubMed Web of Science ®Google Scholar
• Raggi P, Chertow GM, Torres PU, et al. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant. 2011;26(4):1327–1339.
   PubMed Web of Science ®Google Scholar
• Zingraff J, Drueke T, Marie P, et al. Anemia and secondary hyperparathyroidism. Arch Intern Med. 1978 Nov;138(11):1650–1652.
   PubMedGoogle Scholar
• Rao DS, Shih MS, Mohini R. Effect of serum parathyroid hormone and bone marrow fibrosis on the response to erythropoietin in uremia. N Engl J Med. 1993 Jan;328(3):171–175.
   PubMed Web of Science ®Google Scholar
• Bogin E, Massry SG, Levi J, et al. Effect of parathyroid hormone on osmotic fragility of human erythrocytes. J Clin Invest. 1982 Apr;69(4):1017–1025.
   PubMed Web of Science ®Google Scholar
• Akmal M, Telfer N, Ansari AN, et al. Erythrocyte survival in chronic renal failure. Role of secondary hyperparathyroidism. J Clin Invest. 1985 Oct;76(4):1695–1698.
   PubMed Web of Science ®Google Scholar
• Trunzo JA, McHenry CR, Schulak JA, et al. Effect of parathyroidectomy on anemia and erythropoietin dosing in end-stage renal disease patients with hyperparathyroidism. Surgery. 2008 Dec;144(6):915–918. discussion 919.
   PubMed Web of Science ®Google Scholar
• Tanaka M, Yoshida K, Fukuma S, et al. Effects of secondary hyperparathyroidism treatment on improvement in anemia: results from the MBD-5D study. PLoS One. 2016;11(10):e0164865.
   PubMed Web of Science ®Google Scholar
• Goicoechea M, Vazquez MI, Ruiz MA, et al. Intravenous calcitriol improves anaemia and reduces the need for erythropoietin in haemodialysis patients. Nephron. 1998;78(1):23–27.
   PubMed Web of Science ®Google Scholar
• Sarnak MJ, Jaber BL. Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int. 2000 Oct;58(4):1758–1764.
   PubMed Web of Science ®Google Scholar
• Young EW, Albert JM, Satayathum S, et al. Predictors and consequences of altered mineral metabolism: the dialysis outcomes and practice patterns study. Kidney Int. 2005 Mar;67(3):1179–1187.
   PubMed Web of Science ®Google Scholar
• Kir S, Komaba H, Garcia AP, et al. PTH/PTHrP receptor mediates cachexia in models of kidney failure and cancer. Cell Metab. 2016;23(2):315–323.
   PubMed Web of Science ®Google Scholar
• Kir S, White JP, Kleiner S, et al. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature. 2014 Sep;513(7516):100–104.
   PubMed Web of Science ®Google Scholar
• Drueke T, Fauchet M, Fleury J, et al. Effect of parathyroidectomy on left-ventricular function in haemodialysis patients. Lancet. 1980 Jan;1(8160):112–114.
   PubMed Web of Science ®Google Scholar
• Lavi-Moshayoff V, Wasserman G, Meir T, et al. PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol. 2010 Oct;299(4):F882–9.
   PubMed Web of Science ®Google Scholar
• Fukagawa M, Kido R, Komaba H, et al. Abnormal mineral metabolism and mortality in hemodialysis patients with secondary hyperparathyroidism: evidence from marginal structural models used to adjust for time-dependent confounding. Am J Kidney Dis. 2014 Jun;63(6):979–987.
   PubMed Web of Science ®Google Scholar
• Di Iorio B, Molony D, Bell C, et al. Sevelamer versus calcium carbonate in incident hemodialysis patients: results of an open-label 24-month randomized clinical trial. Am J Kidney Dis. 2013 Oct;62(4):771–778.
   PubMed Web of Science ®Google Scholar
• Palmer SC, Gardner S, Tonelli M, et al. Phosphate-binding agents in adults with CKD: a network meta-analysis of randomized trials. Am J Kidney Dis. 2016 Nov;68(5):691–702.
   PubMed Web of Science ®Google Scholar
• Block GA, Raggi P, Bellasi A, et al. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int. 2007 Mar;71(5):438–441.
   PubMed Web of Science ®Google Scholar
• Kidney Disease: Improving Global Outcomes CKD-MBD Work Group. KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease–mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2017;7(1):1–59.
   Web of Science ®Google Scholar
• Fukagawa M, Yumita S, Akizawa T, et al. Cinacalcet (KRN1493) effectively decreases the serum intact PTH level with favorable control of the serum phosphorus and calcium levels in Japanese dialysis patients. Nephrol Dial Transplant. 2008;23(1):328–335.
   PubMed Web of Science ®Google Scholar
• Komaba H, Nakanishi S, Fujimori A, et al. Cinacalcet effectively reduces parathyroid hormone secretion and gland volume regardless of pretreatment gland size in patients with secondary hyperparathyroidism. Clin J Am Soc Nephrol. 2010;5(12):2305–2314.
   PubMed Web of Science ®Google Scholar
• Chiu YW, Teitelbaum I, Misra M, et al. Pill burden, adherence, hyperphosphatemia, and quality of life in maintenance dialysis patients. Clin J Am Soc Nephrol. 2009 Jun;4(6):1089–1096.
   PubMed Web of Science ®Google Scholar
• Fukagawa M, Yokoyama K, Shigematsu T, et al. A phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of etelcalcetide (ONO-5163/AMG 416), a novel intravenous calcimimetic, for secondary hyperparathyroidism in Japanese haemodialysis patients. Nephrol Dial Transplant. 2017 Oct;32(10):1723–1730.
   PubMed Web of Science ®Google Scholar
• Block GA, Bushinsky DA, Cunningham J, et al. Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: two randomized clinical trials. JAMA. 2017 Jan;317(2):146–155.
   PubMed Web of Science ®Google Scholar
• Block GA, Bushinsky DA, Cheng S, et al. Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: a randomized clinical trial. JAMA. 2017 Jan;317(2):156–164.
   PubMed Web of Science ®Google Scholar
• Miyazaki H, Ikeda Y, Sakurai O, et al. Discovery of evocalcet, a next-generation calcium-sensing receptor agonist for the treatment of hyperparathyroidism. Bioorg Med Chem Lett. 2018 Jun;28(11):2055–2060.
   PubMed Web of Science ®Google Scholar
• Bonn B, Masimirembwa CM, Aristei Y, et al. The molecular basis of CYP2D6-mediated N-dealkylation: balance between metabolic clearance routes and enzyme inhibition. Drug Metab Dispos. 2008 Nov;36(11):2199–2210.
   PubMed Web of Science ®Google Scholar
• Leach K, Gregory KJ, Kufareva I, et al. Towards a structural understanding of allosteric drugs at the human calcium-sensing receptor. Cell Res. 2016 05;26(5):574–592.
   PubMed Web of Science ®Google Scholar
• Kawata T, Tokunaga S, Murai M, et al. A novel calcimimetic agent, evocalcet (MT-4580/KHK7580), suppresses the parathyroid cell function with little effect on the gastrointestinal tract or CYP isozymes in vivo and in vitro. PLoS One. 2018;13(4):e0195316.
   PubMed Web of Science ®Google Scholar
• Kondo Y, Kato T, Hosomi A, et al. [The effects of cinacalcet on vagus nerve in miniature pigs]. Jin to Toseki [Kidney and dialysis]. 2017;82(3):455–460. Japanese.
   Google Scholar
• Boussios S, Pentheroudakis G, Katsanos K, et al. Systemic treatment-induced gastrointestinal toxicity: incidence, clinical presentation and management. Ann Gastroenterol. 2012;25(2):106–118.
   PubMedGoogle Scholar
• Badary OA, Awad AS, Sherief MA, et al. In vitro and in vivo effects of ferulic acid on gastrointestinal motility: inhibition of cisplatin-induced delay in gastric emptying in rats. World J Gastroenterol. 2006 Sep;12(33):5363–5367.
   PubMed Web of Science ®Google Scholar
• Tokunaga S, Endo Y, Kawata T. Pharmacological and clinical profiles of a novel calcimimetic, evocalcet (ORKEDIA ®). Nihon Yakurigaku Zasshi [Folia Pharmacologica Japonica]. 2019;154(1):35–43. Japanese.
   PubMedGoogle Scholar
• Narushima K, Maeda H, Shiramoto M, et al. Assessment of CYP-mediated drug interactions for evocalcet, a new calcimimetic agent, based on in vitro investigations and a cocktail study in humans. Clin Transl Sci. 2019 Jan;12(1):20–27.
   PubMed Web of Science ®Google Scholar
• Akizawa T, Shimazaki R, Fukagawa M, et al. Phase 2b study of evocalcet (KHK7580), a novel calcimimetic, in Japanese patients with secondary hyperparathyroidism undergoing hemodialysis: A randomized, double-blind, placebo-controlled, dose-finding study. PLoS One. 2018;13(10):e0204896.
   PubMed Web of Science ®Google Scholar
• Fukagawa M, Shimazaki R, Akizawa T, et al. Head-to-head comparison of the new calcimimetic agent evocalcet with cinacalcet in Japanese hemodialysis patients with secondary hyperparathyroidism. Kidney Int. 2018 Oct;94(4):818–825.
   PubMed Web of Science ®Google Scholar
• Yokoyama K, Shimazaki R, Fukagawa M, et al. Long-term efficacy and safety of evocalcet in Japanese patients with secondary hyperparathyroidism receiving hemodialysis. Sci Rep. 2019 Apr;9(1):6410.
   PubMedGoogle Scholar
• Tsuruya K, Shimazaki R, Fukagawa M, et al. Efficacy and safety of evocalcet in Japanese peritoneal dialysis patients. Clin Exp Nephrol. 2019 Jun;23(6):739–748.
   PubMed Web of Science ®Google Scholar
• Akizawa T, Shimazaki R, Shiramoto M, et al. Pharmacokinetics, pharmacodynamics, and safety of the novel calcimimetic agent evocalcet in healthy Japanese subjects: first-in-human phase I study. Clin Drug Investig. 2018 Oct;38(10):945–954.
   PubMed Web of Science ®Google Scholar
• Shigematsu T, Shimazaki R, Fukagawa M, et al. Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving hemodialysis: first-in-patient clinical trial in Japan. Clin Pharmacol. 2018;10:101–111.
   PubMed Web of Science ®Google Scholar
• Shigematsu T, Shimazaki R, Fukagawa M, et al. Pharmacodynamics of evocalcet for secondary hyperparathyroidism in Japanese hemodialysis patients. Clin Exp Nephrol. 2019 Feb;23(2):258–267.
   PubMed Web of Science ®Google Scholar
• Tominaga Y, Kakuta T, Yasunaga C, et al. Evaluation of parathyroidectomy for secondary and tertiary hyperparathyroidism by the parathyroid surgeons’ society of Japan. Ther Apher Dial. 2016;20(1):6–11.
   PubMed Web of Science ®Google Scholar
• Fukagawa M, Fukuma S, Onishi Y, et al. Prescription patterns and mineral metabolism abnormalities in the cinacalcet era: results from the MBD-5D study. Clin J Am Soc Nephrol. 2012;7(9):1473–1480.
   PubMed Web of Science ®Google Scholar
• Moe SM, Abdalla S, Chertow GM, et al. Effects of cinacalcet on fracture events in patients receiving hemodialysis: the EVOLVE trial. J Am Soc Nephrol. 2015;26(6):1466–1475.
   PubMed Web of Science ®Google Scholar
• Wheeler DC, London GM, Parfrey PS, et al. Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial. J Am Heart Assoc. 2014;3(6):e001363.
   PubMed Web of Science ®Google Scholar
• Wakasugi M, Kazama JJ, Wada A, et al. Hip fracture trends in Japanese dialysis patients, 2008–2013. Am J Kidney Dis. 2018 Feb;71(2):173–181.
   PubMed Web of Science ®Google Scholar
• Díaz-Tocados JM, Rodríguez-Ortiz ME, Almadén Y, et al. Calcimimetics maintain bone turnover in uremic rats despite the concomitant decrease in parathyroid hormone concentration. Kidney Int. 2019 May;95(5):1064–1078.
   PubMed Web of Science ®Google Scholar
• Kawata T, Nagano N, Obi M, et al. Cinacalcet suppresses calcification of the aorta and heart in uremic rats. Kidney Int. 2008 Nov;74(10):1270–1277.
   PubMed Web of Science ®Google Scholar
• Sakai M, Tokunaga S, Kawai M, et al. Evocalcet prevents ectopic calcification and parathyroid hyperplasia in rats with secondary hyperparathyroidism. PLoS One. 2020;15(4):e0232428.
   PubMed Web of Science ®Google Scholar
• Hamano N, Komaba H, Fukagawa M. Etelcalcetide for the treatment of secondary hyperparathyroidism. Expert Opin Pharmacother. 2017 Apr;18(5):529–534.
   PubMed Web of Science ®Google Scholar
• Cunningham J, Block GA, Chertow GM, et al. Etelcalcetide is effective at all levels of severity of secondary hyperparathyroidism in hemodialysis patients. Kidney Int Rep. 2019 Jul;4(7):987–994.
   PubMed Web of Science ®Google Scholar