Research Progress in Ubrogepant

doi:10.19803/j.1672-8629.2021.03.18

Abstract

Abstract: ：Ubrogepant (trade name: Ubralvy) is an oral, small molecule, highly selective, calcitonin gene-related peptide receptor antagonist (CGRP P-receptor) , which won the first approval of FDA for the treatment of episodic migraine by inhibiting CRGP activity. Compared with conventional drugs for acute migraine, ubrogepant can prevent the episode of acute migraine and reduce the number of episodes, which is better tolerated and has fewer contraindications. This article reviews the mechanism, pharmacokinetics, pharmacodynamics, clinical evaluation and safety of ubrogepant in order toprovide reference for clinical treatment and further research.

Key words: ubrogepant, acute migraine, small molecule oral medicine

CLC Number:

R994.13

ZHAO Shuang, CHEN Hongying, MIAO Qiuli, LIU Weibing, SONG Yanqing. Research Progress in Ubrogepant[J]. Chinese Journal of Pharmacovigilance, 2021, 18(3): 289-293.

References

[1] Lassen LH, Jacobsen VB, Haderslev PA, et al.Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients[J]. Neuroreport, 2001, 12( 5) : 967-971.
[2] Vos T, Flaxman AD, Naghavi M, et al.Years lived with disability (YLDs) for 1 160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the global burden of disease study 2010[J]. Lancet, 2012, 380(9859): 2163-2196.
[3] Lipton RB, Stewart WF, Diamond S, et al.Prevalence and burden of migraine in the United States: data from the American Migraine Study II[J]. Headache, 2001, 41(7) : 646-657.
[4] Lassen LH, Jacobsen VB, Haderslev PA, et al.Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients[J]. Neuroreport, 2001, 12(5) : 967-971.
[5] Vos T, Flaxman AD, Naghavi M, et al.Years lived with disability ( YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Dis-ease Study 2010[J].Lancet, 2012, 380: 2163-2196.
[6] Allergan. Ubrelvy (ubrogepant): US prescribing information[EB/OL]. (2020-02-05)[2020-04-01]. http://www.fda.gov.
[7] Jakate A, Boinpally R, Butler M, et al.Single therapeutic doses of ubrogepant are not associated with a clinically relevant drug-drug interaction when co-administered with acetaminophen or naproxen[J]. Headache, 2019, 59(1): 87-88.
[8] Voss T, Lipton RB, Dodick DW, et al.A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine[J]. Cephalalgia, 2016, 36(9): 887-898.
[9] Li CC, Voss T, Kowalski K, et al.Making better dose decisions: using exposure-response modeling to integrate efficacy outcome of two phase 2b clinical trials of ubrogepant for migraine treatmen[J]Clin Transl Sci, 2020, 13(3): 482-490.
[10] Lipton RB, Ailani J, Hutchinson S, et al.Efficacy is maintained with long-term intermittent use of ubrogepant for the acute treatment of migraine[J]. Headache, 2019, 60(1): 141-152.
[11] Ankrom W, Bondiskey P, Li CC, et al.Ubrogepant is not associated with clinically meaningful elevations of alanine aminotransferase in healthy adult males[J]. Clin Transl Sci, 2020, 13(3): 462-472.
[12] Goadsby PJ, Tepper SJ, Watkins PB, et al.Safety and tolerability of ubrogepant following intermittent, high-frequency dosing: randomized, placebo-controlled trial in healthy adults[J]. Cephalalgia, 2019, 39(14): 1753-1761.
[13] Hutchinson S, Dodick DW, Treppendahl C, et al.Ubrogepant for the acute treatment of migraine: pooled safety and tolerability from ACHIEVE I and ACHIEVE II phase 3 studies[J]. Headache, 2019, 59(Suppl (1): 120.
[14] Hutchinson S, Silberstein SD, Blumenfeld AM, et al.Safety of ubrogepant in participants with moderate to high cardiovascular risk[J]. Headache, 2019, 59(Suppl 1): 104-105.
[15] Ailani J, Lipton RB, Hutchinson S, et al.Long-term safety evaluation of ubrogepant for the acute treatment of migraine; phase 3, randomized, 52-week extension trial[J]. Headache, 2020, 60(1): 141-152.
[16] Moore E, Burgey CS, Fraley M, et al.Characterization of ubrogepant: a potent and selective antagonist of the human calcitonin gene-related peptide receptor[J]. Journal of Pharmacology and Experimental Therapeutics April, 2020, 373(1): 160-166.
[17] Jakate A, Boinpally R, Butler M, et al.Single therapeutic and supratherapeutic doses of ubrogepant do not affect cardiac repolarization in healthy adults: results from a randomized trial. Clin Pharmacol Ther[J]. Clin Pharmacol Ther, 2020, 107(4):1014-1022.
[18] Connor KM, Shapiro RE, Diener HC, et al.Randomized,controlled trial of telcagepant for the acute treatment of migraine[J].Neurology, 2009, 3(12) : 970-977.
[19] Moore E, Fraley ME, Bell IM, et al.Characterization of ubrogepant: a potent and selective antagonist of the human calcitonin gene?related peptide receptor[J]. Journal of Pharmacology and Experimental Therapeutics, 2020, 372(3) : 970-977.
[20] Li CC, Dockendorf M,Kowalski K, et al.Population PK analyses of ubrogepant MK-1602), a CGRP receptor antagonist: enriching in-clinic plasma pk sampling with outpatient dried blood spot sampling[J]. Clin Pharmacol, 2018, 58(3): 294-303.
[21] Peter J,Stewart J,Paul B Watkins,Safety and tolerability of ubrogepant following intermittent, high-frequency dosing: Randomized, placebo-controlled trial in healthy adults[J].Cephalalgia, 2019, 39(14): 1753-1761.
[22] Li C, Palcza J, Xu J, et al.Absence of clinically significant drug interactions with coadministration of ubrogepant and an ethinyl estradiol/norgestimate oral contraceptive in healthy female subjects: a phase 1 pharmacokinetic analysis[J]. Headache, 2019, 59(1): 91.
[23] Jakate A, Boinpally R, Butler M, et al.Single therapeutic doses of ubrogepant are not associated with a clinically relevant drug-drug interaction when co-administered with acetaminophen or naproxen[J]. Headache, 2019, 59(1):87-88.
[24] Jakate A, Boinpally R, Butler M, et al.Coadministration of single therapeutic oral doses of ubrogepant and sumatriptan produces no clinically relevant pharmacokinetic interactions[J]. Headache, 2019, 59(1): 86-87.
[25] Goadsby PJ, Tepper SJ, Watkins PB, et al.Safety and tolerability of ubrogepant following intermittent, high-frequency dosing: randomized, placebo-controlled trial in healthy adults[J]. Cephalalgia, 2019, 39(14): 1753-1761.
[26] Croop R, Goadsby PJ, Stock DA, et al.Efficacy,safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind,placebo-controlled trial[J]. Lancet, 2019, 394(10200): 737-745.