OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Eptinezumab – Vyepti®

DRUG CLASS

Migraine Headache Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

ANNOTATED BIBLIOGRAPHY

References updated: 09 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 eptinezumab).
• FDA. https://www​.accessdata​.fda.gov/drugsatfda_docs​/nda/2020/761119Orig1s000SumR.pdf.

  (FDA Drug Approvals website that has product labels [package inserts], letters of approval and full FDA multidisciplinary scientific review of the eptinezumab application which mentions safety results in Section 8, page 16).
• Dodick DW, Lipton RB, Silberstein S, Goadsby PJ, Biondi D, Hirman J, Cady R, et al. Eptinezumab for prevention of chronic migraine: A randomized phase 2b clinical trial. Cephalalgia. 2019;39:1075–85. [PubMed: 31234642]

  (Among 616 adults with chronic migraine treated with eptinezumab [10, 30, 100 or 300 mg] or placebo as a single intravenous infusion, a 75% reduction in number of migraine days per month occurred in 27%, 28%, 31% and 33% on drug vs 21% on placebo, and adverse events were mostly mild upper respiratory symptoms and dizziness; there were no serious adverse events and data on ALT levels were not reported).
• Ashina M, Saper J, Cady R, Schaeffler BA, Biondi DM, Hirman J, Pederson S, et al. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia. 2020;40:241–54. [PMC free article: PMC7066477] [PubMed: 32075406]

  (Among 888 patients with episodic migraine treated with eptinezumab [30, 100 or 300 mg] vs placebo intravenously every 12 weeks for 48 weeks, the reduction in number of migraine days per month averaged -4.0, -3.9, -4.2 on drug vs -3.2 on placebo, and adverse events that were more frequent with drug were upper respiratory symptoms and fatigue; no mention of ALT elevations or hepatotoxicity).
• Lipton RB, Goadsby PJ, Smith J, Schaeffler BA, Biondi DM, Hirman J, Pederson S, et al. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology. 2020;94:e1365–e1377. [PMC free article: PMC7274916] [PubMed: 32209650]

  (Among 1072 patients with chronic migraine treated with eptinezumab [100 or 300 mg] vs placebo intravenously at week 0 and 12, average number of migraine days per month decreased by 7.7 and 8.2 with eptinezumab and by 5.6 days with placebo, and adverse events were uncommon and usually mild, the most frequent being nasopharyngitis [9.4% vs 6%] and fatigue [1.8% vs <1%], and there were no hepatic adverse events and no mention of ALT elevations).
• Dhillon S. Eptinezumab: first approval. Drugs. 2020;80(7):733–9. [PubMed: 32266704]

  (Review of the mechanism of action, history of development, clinical efficacy and safety of eptinezumab shortly after its approval for use in the US, mentions side effects of fatigue and dizziness, but does not mention ALT elevations or hepatotoxicity).
• Eptinezumab (Vyepti) for migraine prevention. Med Lett Drugs Ther. 2020;62(1599):85–7. [PubMed: 32555116]

  (Concise review of the mechanism of action, clinical efficacy, safety and costs of eptinezumab in relation to other drugs for migraine prevention shortly after its approval in the US, states that it is modestly effective and that adverse events include nasopharyngitis and hypersensitivity reactions [1-2%] including angioedema; no mention of ALT elevations or hepatotoxicity).
• 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 and ergots] and to prevent migraines [such as anticonvulsants, beta blockers, antidepressants and CGRP antagonists]).
• Silberstein S, Diamond M, Hindiyeh NA, Biondi DM, Cady R, Hirman J, Allan B, et al. Eptinezumab for the prevention of chronic migraine: efficacy and safety through 24 weeks of treatment in the phase 3 PROMISE-2 (Prevention of migraine via intravenous ALD403 safety and efficacy-2) study. J Headache Pain. 2020;21:120. [PMC free article: PMC7539382] [PubMed: 33023473]

  (Among 1072 adults with chronic migraine treated with eptinezumab [100 or 300 mg] vs placebo intravenously at 0 and 12 weeks, the reduction in days with migraine per month decreased by week 24 by 8.2 and 8.8 days vs 6.2 days with placebo, and no new adverse events were reported compared to [compared to Lipton 2020], hypersensitivity reactions occurring in 3 patients [0.9%] with the second dose; no mention of ALT elevations or hepatotoxicity).
• Smith TR, Janelidze M, Chakhava G, Cady R, Hirman J, Allan B, Pederson S, et al. Eptinezumab for the prevention of episodic migraine: sustained effect through 1 year of treatment in the PROMISE-1 Study. Clin Ther. 2020;42:2254–65.e3. [PubMed: 33250209]

  (Among 888 patients with episodic migraine treated with eptinezumab [30, 100, 300 mg] vs placebo intravenously every 12 weeks for up to one year, reductions in average number of days with migraine per month were 4 to 4.8 with eptinezumab vs 3.2 to 4.6 with placebo, and adverse events rates were similar in all groups and decreased after the initial dose, and “no serious tolerability signals were observed”).
• Kudrow D, Cady RK, Allan B, Pederson SM, Hirman J, Mehta LR, Schaeffler BA. Long-term safety and tolerability of eptinezumab in patients with chronic migraine: a 2-year, open-label, phase 3 trial. BMC Neurol. 2021;21:126. [PMC free article: PMC7977171] [PubMed: 33740902]

  (Among 128 adults with chronic migraine treated with eptinezumab [300 mg] intravenously every 12 weeks for up to 2 years, adverse events included upper respiratory tract symptoms and a low rate of hypersensitivity reactions [5 patients], one of which was moderate and responded rapidly to an infusion of antihistamine; in addition, “No clinically relevant trends in clinical laboratory….results were identified”).
• Smith TR, Spierings ELH, Cady R, Hirman J, Schaeffler B, Shen V, Sperling B, et al. Safety and tolerability of eptinezumab in patients with migraine: a pooled analysis of 5 clinical trials. J Headache Pain. 2021;22:16. [PMC free article: PMC8008612] [PubMed: 33781209]

  (Analysis of safety based upon pooled results from five placebo controlled trials of eptinezumab in 2867 patients with migraine found an overall treatment-emergent adverse event ate of 55% [1.7% severe] with drug vs 52% [1.4% severe] with placebo, and most events were considered unrelated, although infusion related hypersensitivity reactions occurred in 1.1% of eptinezumab vs 0% of placebo recipients).
• Winner PK, McAllister P, Chakhava G, Ailani J, Ettrup A, Krog Josiassen M, Lindsten A, et al. Effects of intravenous eptinezumab vs placebo on headache pain and most bothersome symptom when initiated during a migraine attack: a randomized clinical trial. JAMA. 2021;325:2348–56. [PMC free article: PMC8207242] [PubMed: 34128999]

  (Among 476 adults who were treated with an intravenous infusion within 1 to 6 hours of onset of a migraine headache, the time to being pain free was shorter with 100 mg of eptinezumab than placebo [4 vs 9 hours] and adverse event rates were similar except for hypersensitivity reactions [2.1% vs none]; no mention of hepatic adverse events or ALT elevations).