Chemistry:Fremanezumab

From HandWiki
Short description: Pharmaceutical biological monoclonal antibody
Fremanezumab
AJOVY.jpg
A Norwegian syringe of fremanezumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetCalcitonin gene-related peptide (CGRP) α, β
Clinical data
Trade namesAjovy
Other namesTEV-48125, fremanezumab-vfrm
AHFS/Drugs.comMonograph
MedlinePlusa618053
License data
Pregnancy
category
Routes of
administration		Subcutaneous
Drug classCalcitonin gene-related peptide antagonist
ATC code
Legal status
Legal status
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

Fremanezumab, sold under the brand name Ajovy, is a medication used to prevent migraines in adults.[8][6] It is given by injection under the skin.[8][6]

The most common side effect is pain and redness at the site of injection.[8] Other side effects include allergic reactions.[8] It is in the calcitonin gene-related peptide antagonist class of medications.[8]

It was approved for medical use in the United States in 2018,[8] the European Union in 2019,[7] the UK in 2020[4] and Argentina by September 2021.[9]

Medical uses

Fremanezumab was shown to be effective in adults with four or more attacks per month.[10]

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.[6][11]

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.[6]

Pharmacology

Mechanism of action

Fremanezumab is a fully humanized monoclonal antibody directed against calcitonin gene-related peptides (CGRP) alpha and beta.[12] The precise mechanism of action is unknown.[11] It 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.[11]

History

Fremanezumab was discovered and developed by Rinat Neuroscience, was acquired by Pfizer in 2006, and was then licensed to Teva.[13] It was approved by the US Food and Drug Administration in September 2018.[14] In March 2019, fremanezumab was approved for marketing and use in the European Union.[7][15]

The drug has been and is still[when?] being evaluated for diseases other than migraine, where the endogenous substance CGRP has been implicated in the pathology.[citation needed] Teva is still[when?] 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.[16][needs update]

Chemistry

Fremanezumab is a humanized monoclonal antibody.[17] It is produced using recombinant DNA in Chinese hamster ovary cells.[18]

References

  1. ↑ "Fremanezumab (Ajovy) Use During Pregnancy". 3 October 2018. https://www.drugs.com/pregnancy/fremanezumab.html. 
  2. ↑ "Summary Basis of Decision (SBD) for Ajovy". https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00479&lang=en. 
  3. ↑ "Ajovy Product information". https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=98765. 
  4. ↑ 4.0 4.1 "Fremanezumab". https://bnf.nice.org.uk/drug/fremanezumab.html. 
  5. ↑ "Ajovy (fremanezumab) 225 mg Pre-filled Syringe for Injection - Summary of Product Characteristics (SmPC)". https://www.medicines.org.uk/emc/product/10386/smpc. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 "Ajovy- fremanezumab-vfrm injection". DailyMed. U.S. National Library of Medicine. 5 February 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=98e344ea-5916-4947-b6f2-4a76ccc04b6b. 
  7. ↑ 7.0 7.1 7.2 "Ajovy EPAR". 29 January 2019. https://www.ema.europa.eu/en/medicines/human/EPAR/ajovy. 
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 "Fremanezumab-vfrm Monograph for Professionals". American Society of Health-System Pharmacists. https://www.drugs.com/monograph/fremanezumab-vfrm.html. 
  9. ↑ "Migraña: en qué consiste el nuevo tratamiento para esta enfermedad frecuente e incapacitante". https://www.infobae.com/salud/ciencia/2021/09/12/migrana-en-que-consiste-el-nuevo-tratamiento-para-esta-enfermedad-frecuente-e-incapacitante/. 
  10. ↑ "Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial". JAMA 319 (19): 1999–2008. May 2018. doi:10.1001/jama.2018.4853. PMID 29800211. 
  11. ↑ 11.0 11.1 11.2 "Ajovy: EPAR - Product Information". European Medicines Agency. 2019-04-17. https://www.ema.europa.eu/documents/product-information/ajovy-epar-product-information_en.pdf. 
  12. ↑ "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 77". WHO Drug Information 31 (1): 61–150. 2017. 
  13. ↑ "Fremanezumab - Teva Pharmaceutical". https://adis.springer.com/drugs/800024333. 
  14. ↑ "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.". https://www.tevapharm.com/news/teva_announces_u_s_approval_of_ajovytm_fremanezumab_vfrm_injection_the_first_and_only_anti_cgrp_treatment_with_both_quarterly_and_monthly_dosing_for_the_preventive_treatment_of_migraine_in_adults_09_18.aspx. 
  15. ↑ "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.
  16. ↑ "Teva Pulls Out of Chronic Cluster Headache Trial of Fremanezumab". http://www.mdmag.com/medical-news/teva-pulls-out-of-chronic-cluster-headache-trial-of-fremanezumab. 
  17. ↑ "Novel class of preventive treatments for migraine - Clinical Advisor". 18 May 2020. https://www.clinicaladvisor.com/home/topics/neurology-information-center/novel-class-of-preventive-treatments-for-migraine/. 
  18. ↑ "AJOVY prescribing information". https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761089s000lbl.pdf. 

External links



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Fremanezumab&oldid=3333667"