Evolocumab

Evolocumab[2] (trade name Repatha) is a monoclonal antibody designed for the treatment of hyperlipidemia.

Evolocumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetPCSK9
Clinical data
Trade namesRepatha
Other namesAMG-145[1]
AHFS/Drugs.comhttps://www.drugs.com/repatha.html
License data
Routes of
administration		Subcutaneous injection
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6242H9648N1668O1996S56
Molar mass141.8 kg/mol g·mol−1

Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL-C, or "bad" cholesterol, from the blood.[3]

In 2015 it cost about US$14,100 per year. One article calculated this to be about $400,000 to $500,000 per quality-adjusted life year (QALY), which did not meet "generally accepted" cost-benefit thresholds. The authors calculated that an annual cost of $4,500 would meet an acceptable $100,000 per QALY standard.[4] It is made by Amgen. On October 26, 2018 Amgen announced a 60% cut in price and the drug now costs $5,850 per year.[5]

Mechanism

Evolocumab is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of liver cells to remove LDL-C from the blood.[6]

History

Amgen submitted a biologics license application (BLA) for evolocumab to the FDA in August 2014.[7] The FDA approved evolocumab injection on 27 August 2015, for some patients who are unable to get their LDL cholesterol under control with current treatment options.[8] The European Commission approved it in July 2015.[9] Evolocumab received approval from Health Canada on September 10, 2015.[10] Amgen reported approval by Health Canada in a press release on September 15, 2015.[11]

Regeneron Pharmaceuticals and Amgen had each filed for patent protection on their monoclonal antibodies against PCSK9 and the companies ended up in patent litigation in the U.S. In March 2016 a district court found that Regeneron's drug alirocumab infringed Amgen's patents; Amgen then requested an injunction barring Regeneron and Sanofi from marketing alirocumab, which was granted in January 2017. The judge gave Regeneron and Sanofi 30 days to appeal before the injunction went into effect.[12]

Results of the FOURIER trial were published in March 2017.[13]

References
  1. Sheridan, C (2013). "Phase 3 data for PCSK9 inhibitor wows". Nature Biotechnology. 31 (12): 1057–8. doi:10.1038/nbt1213-1057. PMID 24316621.
  2. World Health Organization (2012). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 108" (PDF). WHO Drug Information. 26 (4).
  3. Weinreich, M; Frishman, W (2014). "Antihyperlipidemic therapies targeting PCSK9". Cardiology in Review. 22 (3): 140–6. doi:10.1097/CRD.0000000000000014. PMID 24407047.
  4. Kazi, Dhruv S.; Moran, Andrew E.; Coxson, Pamela G.; Penko, Joanne; Ollendorf, Daniel A.; Pearson, Steven D.; Tice, Jeffrey A.; Guzman, David; Bibbins-Domingo, Kirsten (16 August 2016). "Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease". JAMA. 316 (7): 743–53. doi:10.1001/jama.2016.11004. PMID 27533159.
  5. Goldman, Dana. "The bigger message behind Amgen's decision to slash cost of its Repatha cholesterol drug". MarketWatch. Retrieved 2018-10-28.
  6. "PCSK9 инхибитори – нов клас медикаменти за лечение на дислипидемия | Списание МД". spisaniemd.bg. Retrieved 2018-10-28.
  7. Amgen Submits Biologics License Application For Novel Investigational LDL Cholesterol-Lowering Medication Evolocumab To The FDA
  8. FDA News Release (August 27, 2015). "FDA approves Repatha to treat certain patients with high cholesterol". U.S. Food and Drug Administration. Retrieved 30 August 2015.
  9. European Commission Approves Amgen's New Cholesterol-Lowering Medication Repatha™ (evolocumab), The First PCSK9 Inhibitor To Be Approved In The World, For Treatment Of High Cholesterol
  10. "Regulatory Decision Summary (SBD): REPATHA - 2015 - Health Canada". www.hc-sc.gc.ca. Archived from the original on 2015-10-07. Retrieved 2015-10-06.
  11. "Amgen - Media - In The News". www.amgen.ca. Retrieved 2015-09-17.
  12. Feeley, Jef; Bloomfield, Doni; Decker, Susan (5 January 2017). "Amgen Wins Ban on Sanofi's Praluent Cholesterol Drug Sales". Bloomberg News.
  13. S., Sabatine, Marc; P., Giugliano, Robert; C., Keech, Anthony; Narimon, Honarpour; D., Wiviott, Stephen; A., Murphy, Sabina; F., Kuder, Julia; Huei, Wang; Thomas, Liu (2017-03-17). "Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease — NEJM" (PDF). New England Journal of Medicine. 376 (18): 1713–1722. doi:10.1056/nejmoa1615664. PMID 28304224.
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