Fremanezumab

Fremanezumab, sold under the brand name Ajovy, is a medication used to prevent migraines in adults.[2][3] It is given by injection under the skin.[2][3]

Fremanezumab
A Norwegian syringe of fremanezumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetCGRP α, β
Clinical data
Trade namesAjovy
Other namesTEV-48125, fremanezumab-vfrm
AHFS/Drugs.comMonograph
MedlinePlusa618053
License data
Pregnancy
category
    Routes of
    administration    		Subcutaneous injection
    Drug classCalcitonin gene-related peptide antagonist
    ATC code
    Legal status
    Legal status
    • US: ℞-only
    • In general: ℞ (Prescription only)
    Pharmacokinetic data
    Bioavailability55–66%
    MetabolismProteolysis
    Elimination half-life30–31 days (estimated)
    ExcretionKidney
    Identifiers
    CAS Number
    DrugBank
    ChemSpider
    • none
    UNII
    KEGG
    Chemical and physical data
    FormulaC6470H9952N1716O2016S46
    Molar mass145507.54 g·mol−1

    The most common side effect is pain and redness at the site of injection.[2] Other side effects include allergic reactions.[2] It is in the calcitonin gene-related peptide antagonist class of medications.[2]

    It was approved for medical use in the United States in 2018,[2] and in the European Union in 2019.[4] The wholesale cost in the United States as of 2019 is $US 369.90 per month.[5]

    Medical uses

    Fremanezumab was shown to be effective in adults with four or more attacks per month.[6]

    Adverse effects

    The most common adverse effects are reactions at the injection site, which occurred in 43 to 45% of people in studies (as compared to 38% under placebo). Hypersensitivity reactions occurred in fewer than 1% of patients.[3][7]

    Interactions

    Fremanezumab does not interact with other antimigraine drugs such as triptans, ergot alkaloids and analgesics. It is expected to generally have a low potential for interactions because it is not metabolized by cytochrome P450 enzymes.[3]

    Pharmacology

    Mechanism of action

    Fremanezumab is a fully humanized monoclonal antibody directed against calcitonin gene-related peptides (CGRP) alpha and beta.[8] The precise mechanism of action is unknown.[7] It is the only approved anti-CGRP monoclonal antibody that can be given with a quarterly interval.

    Pharmacokinetics

    After subcutaneous injection, fremanezumab has a bioavailability of 55–66%. Highest concentrations in the body are reached after five to seven days. Like other proteins, the substance is degraded by proteolysis to small peptides and amino acids, which are reused or excreted via the kidney. The elimination half-life is estimated to be 30 to 31 days.[7]

    History

    Fremanezumab was discovered and developed by Rinat Neuroscience, was acquired by Pfizer in 2006, and was then licensed to Teva.[9] It was approved by the US Food and Drug Administration in September 2018.[10] In March 2019, fremanezumab was approved for marketing and use in the European Union.[4][11]

    The drug has been and is still being evaluated for diseases other than migraine, where the endogenous substance CGRP has been implicated in the pathology. Teva is still developing it for episodic cluster headache but stopped development of fremanezumab for the treatment of chronic cluster headache in 2018 after the primary endpoint of a Phase III trial was not met.[12]

    Chemistry

    Fremanezumab is a humanized monoclonal antibody. It is partially derived from aborted fetal cell lines not disclosed by the manufacturer as of 2020.[13]

    See also

    Other antibodies blocking the CGRP pathway:

    References
    1. "Fremanezumab (Ajovy) Use During Pregnancy". Drugs.com. 3 October 2018. Retrieved 2 April 2020.
    2. "Fremanezumab-vfrm Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 15 July 2019.
    3. "Ajovy- fremanezumab-vfrm injection". DailyMed. 5 February 2020. Retrieved 2 April 2020.
    4. "Ajovy EPAR". European Medicines Agency (EMA). 29 January 2019. Retrieved 2 April 2020.
    5. "NADAC as of 2019-07-10 | Data.Medicaid.gov". Centers for Medicare and Medicaid Services. Retrieved 15 July 2019.
    6. Dodick, David W.; Silberstein, Stephen D.; Bigal, Marcelo E.; Yeung, Paul P.; Goadsby, Peter J.; Blankenbiller, Tricia; Grozinski-Wolff, Melissa; Yang, Ronghua; Ma, Yuju; Aycardi, Ernesto (15 May 2018). "Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine". JAMA. 319 (19): 1999. doi:10.1001/jama.2018.4853.
    7. "Ajovy: EPAR - Product Information" (PDF). European Medicines Agency. 17 April 2019.
    8. World Health Organization (2017). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 77". WHO Drug Information. 31 (1): 61–150. hdl:10665/330984.
    9. "Fremanezumab - Teva Pharmaceutical".
    10. "Teva Announces U.S. Approval of AJOVY (fremanezumab-vfrm) Injection, the First and Only Anti-CGRP Treatment with Both Quarterly and Monthly Dosing for the Preventive Treatment of Migraine in Adults". Teva Pharmaceutical Industries Ltd Pharmaceutical Industries Ltd. Teva Pharmaceutical Industries Ltd Pharmaceutical Industries Ltd. Retrieved 7 October 2018.
    11. "Teva's AJOVY Receives EU Approval Offering Patients the First and Only Anti-CGRP Treatment with Both Quarterly and Monthly Dosing for the Prophylaxis of Migraine in Adults" (Press release). Teva Pharmaceutical Industries Ltd. 1 April 2019. Retrieved 6 April 2019 – via Business Wire.
    12. "Teva Pulls Out of Chronic Cluster Headache Trial of Fremanezumab". MD Magazine. Retrieved 19 June 2018.
    13. https://www.clinicaladvisor.com/home/topics/neurology-information-center/novel-class-of-preventive-treatments-for-migraine/
    • "Fremanezumab". Drug Information Portal. U.S. National Library of Medicine.
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