OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Ubrogepant – Ubrelvy®

DRUG CLASS

Migraine Headache Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Ubrogepant	1374248-77-7	C29-H26-F3-N5-O3

ANNOTATED BIBLIOGRAPHY

References updated: 20 July 2021

Abbreviations: CGRP, calcitonin gene-related peptide.

• Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.

  (Review of hepatotoxicity published in 1999 before the availability of CGRP antagonists).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2019/211765Orig1s000MedR.pdf.

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA multidisciplinary scientific review of the ubrogepant application including specific discussion of hepatic adverse events which consisted mainly of mild-to-moderate ALT or AST elevations which were similar in frequency in ubrogepant vs placebo recipients and two patients with clinically apparent liver injury had evidence of a pre-existing and unrelated diagnosis; cholecystitis and pancreatitis).
• Ho TW, Connor KM, Zhang Y, Pearlman E, Koppenhaver J, Fan X, Lines C, et al. Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. Neurology. 2014;83:958–66. [PubMed: 25107879]

  (Among 660 patients with migraine enrolled in a controlled trial of telcagepant [140 or 280 mg] vs placebo twice daily for 12 weeks, 13 patients on telcagepant developed ALT elevations above 3 times ULN, generally between weeks 4 and 6 of treatment, and in two instances rising to 33 and 39 times ULN accompanied by symptoms but not jaundice leading to prompt discontinuation and to early termination of the trial because of the risk of significant hepatotoxicity).
• Voss T, Lipton RB, Dodick DW, Dupre N, Ge JY, Bachman R, Assaid C, et al. A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine. Cephalalgia. 2016;36:887–98. [PubMed: 27269043]

  (Among 834 patients treated with ubrogepant [1, 10, 25, 50 or 100 mg] or placebo for an acute attack of migraine, 26% of those receiving 100 mg were headache pain free at 2 hours compared to 9% on placebo, while adverse events more frequent with ubrogepant included low rates of nausea and dizziness and there were no ALT elevations above 3 times ULN).
• Tfelt-Hansen P, Loder E. The Emperor's new gepants: are the effects of the new oral CGRP antagonists clinically meaningful? Headache. 2019;59:113–7. [PubMed: 30451300]

  (Commentary on the relative efficacy of two oral CGRP receptor antagonists, ubrogepant and rimegepant, which show only modest efficacy in acute migraine [therapeutic gain of 5-8%] and only when compared to placebo as compared to well-known effective therapies such as aspirin and other nonsteroidal antiinflammatory agents [8-14%] and the triptans [16-32%]).
• Goadsby PJ, Tepper SJ, Watkins PB, Ayele G, Miceli R, Butler M, Severt L, et al. Safety and tolerability of ubrogepant following intermittent, high-frequency dosing: Randomized, placebo-controlled trial in healthy adults. Cephalalgia. 2019;39:1753–61. [PMC free article: PMC6900570] [PubMed: 31537107]

  (Study of safety of ubrogepant given in intermittent doses [200 mg per day for 2 days] to healthy adults found the overall adverse event rates were the same as with placebo [44% vs 45%], including headache [11% vs 10%] and ALT elevations of 3 times ULN or more [in 5 on placebo and 2 on ubrogepant], which were transient and resolved even with drug continuation and without bilirubin elevations or symptoms).
• Lipton RB, Dodick DW, Ailani J, Lu K, Finnegan M, Szegedi A, Trugman JM. Effect of ubrogepant vs placebo on pain and the most bothersome associated symptom in the acute treatment of migraine: the ACHIEVE II randomized clinical trial. JAMA. 2019;322:1887–98. [PMC free article: PMC6865323] [PubMed: 31742631]

  (Among 1465 adults with an acute migraine headache, freedom from pain at 2 hours was achieved by 21% and 22% of ubrogepant [25 or 50 mg] vs 14% of placebo recipients, while adverse events of nausea and dizziness were generally mild and uncommon [~ 2%] and ALT or AST elevations of at least 3 times ULN arose in only 4 of 966 [<1%] rimegepant treated patients, all of which were transient and without symptoms or jaundice).
• Dodick DW, Lipton RB, Ailani J, Lu K, Finnegan M, Trugman JM, Szegedi A. Ubrogepant for the treatment of migraine. N Engl J Med. 2019;381:2230–41. [PubMed: 31800988]

  (Among 1672 adults with migraine headache, freedom from pain within 2 hours was achieved by 19% and 21% of ubrogepant recipients [50 or 100 mg] vs 12% of placebo recipients, and adverse events of dry mouth, somnolence and nausea were generally mild and uncommon [less than 5%], while ALT or AST elevations of 3 times ULN or greater arose in 0.4% and 0.6% vs 0.2% of patients on placebo).
• Ailani J, Lipton RB, Hutchinson S, Knievel K, Lu K, Butler M, Yu SY, et al. Long-term safety evaluation of ubrogepant for the acute treatment of migraine: phase 3,randomized, 52-week extension trial. Headache. 2020;60:141–52. [PMC free article: PMC7004213] [PubMed: 31913519]

  (Among 1230 adults randomized to ubrogepant [50 or 100 mg] or usual care to treat migraine attacks over a 52 week period, elevations in ALT arose in 31% and 32% on ubrogepant vs 31% on usual care and were above 3 times ULN in 1.3% and 2.7% vs 1%, but none of the elevations were associated with jaundice or symptoms).
• Ankrom W, Bondiskey P, Li CC, Palcza J, Liu W, Dockendorf MF, Matthews C, et al. Ubrogepant is not associated with clinically meaningful elevations of alanine aminotransferase in healthy adult males. Clin Transl Sci. 2020;13:462–72. [PMC free article: PMC7214647] [PubMed: 31899602]

  (In two pharmacokinetic and safety studies conducted in 72 healthy male adults, ubrogepant in single and multiple doses of 40 to 400 mg daily for up to 28 days was well tolerated with no serious adverse events or ALT elevations above 3 times ULN; overall rates of ALT abnormalities were similar to those with placebo).
• Scott LJ. Ubrogepant: first approval. Drugs. 2020;80:323–8. [PMC free article: PMC7062659] [PubMed: 32020557]

  (Review of the mechanism of action, history of development, pharmacology, clinical efficacy and safety of ubrogepant shortly after its approval for use in the US, mentions that ALT or AST elevations above 3 times ULN arose in 1-3% of patients, but none were associated with jaundice and rates were similar between ubrogepant and placebo recipients).
• Lasmiditan (Reyvow) and ubrogepant (Ubrelvy) for acute treatment of migraine. Med Lett Drugs Ther. 2020;62(1593):35–9. [PubMed: 32555120]

  (Concise review of the mechanism of action, clinical efficacy, safety and costs of ubrogepant and lasmiditan as therapy of acute migraine shortly after their approval for this indication in the US, mentions side effects of ubrogepant being nausea and somnolence but does not mention ALT elevations or hepatotoxicity).
• Rimegepant (Nurtec ODT) for acute treatment of migraine. Med Lett Drugs Ther. 2020;62(1597):70–2. [PubMed: 32555113]

  (Concise review of the mechanism of action, pharmacology, clinical efficacy, safety and cost of rimegepant shortly after its approval in the US as therapy of acute migraine in adults, mentions that it “was generally well tolerated in clinical trials; nausea was the most common adverse event [~2%]”).
• Drugs for migraine. Med Lett Drugs Ther. 2020;62(1608):153–60. [PubMed: 33434187]

  (Concise summary of the relative clinical efficacy, safety and costs of drugs to treat acute migraine headache [such as analgesics, opiates, triptans, ergots and oral CGRP receptor antagonists] and to prevent migraines [such as anticonvulsants, beta blockers, antidepressants and the monoclonal antibodies to CGRP and its receptor]).
• Hutchinson S, Dodick DW, Treppendahl C, Bennett NL, Yu SY, Guo H, Trugman JM. Ubrogepant for the acute treatment of migraine: pooled efficacy, safety, and tolerability from the ACHIEVE I and ACHIEVE II phase 3 randomized trials. Neurol Ther. 2021;10:235–49. [PMC free article: PMC8140011] [PubMed: 33608814]

  (Post hoc analysis of efficacy and safety from two controlled trials in 2240 patients with migraine, found pain-free rates at 2 hours to be 20.5% with ubrogepant vs 13% with placebo with similar overall rates of adverse events [11.5% vs 11.2%] and no serious adverse events requiring discontinuation).
• Jakate A, Blumenfeld AM, Boinpally R, Butler M, Borbridge L, Contreras-De Lama J, McGeeney D, et al. Pharmacokinetics and safety of ubrogepant when coadministered with calcitonin gene-related peptide-targeted monoclonal antibody migraine preventives in participants with migraine: A randomized phase 1b drug-drug interaction study. Headache. 2021;61:642–52. [PMC free article: PMC8252052] [PubMed: 33818780]

  (Among 40 patients enrolled in pharmacokinetic studies of ubrogepant with or without concurrent preventive therapy with erenumab or galcanezumab, pharmacokinetic parameters were similar with and without concurrent monoclonal antibodies to CGRP and adverse event rates appeared to be unaffected; there were “no clinically relevant changes in laboratory parameters”).
• Robbins MS. Diagnosis and management of headache: a review. JAMA. 2021;325:1874–85. [PubMed: 33974014]

  (Review of the diagnosis and management of headache including use of calcitonin gene-related peptide antagonists for acute migraine attacks which has uncommon side effects of dry mouth and dizziness; no mention of ALT elevations or hepatotoxicity).