Alirocumab
Monoclonal antibody | |
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Type | Whole antibody |
Source | Human |
Target | Proprotein convertase subtilisin/kexin type 9 (PCSK9) |
Clinical data | |
Trade names | Praluent |
AHFS/Drugs.com | Monograph |
MedlinePlus | a615035 |
License data |
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Pregnancy category |
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Subcutaneous | |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
CAS Number | |
DrugBank | |
ChemSpider |
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UNII | |
KEGG | |
Chemical and physical data | |
Formula | C6472H9996N1736O2032S42 |
Molar mass | 145983.80 g·mol−1 |
Alirocumab, sold under the brand name Praluent, is a
Common side effects include nasopharyngitis (cold), injection site reactions, and influenza.[4]
It was approved for medical use in the United States[4] and in the European Union in 2015.[5]
Medical uses
Alirocumab is used as a
In 2021, the U.S. Food and Drug Administration (FDA) added an indication for alirocumab to treat adults with homozygous familial hypercholesterolemia (HoFH), a genetic condition that causes severely high cholesterol.[4] It is not intended to be used alone but instead added to other treatments for HoFH.[4]
Side effects
Side effects that occurred in more than 2% of people treated with alirocumab in clinical trials and that occurred more frequently than with placebo, included nose and throat irritation, injection site reactions and bruising, flu-like symptoms, urinary tract infection, diarrhea, bronchitis and cough, and muscle pain, soreness, and spasms.[3]
There are no available data on use of alirocumab in pregnant women to assess risks to the fetus, nor is there data on use in children.[3]
Pharmacology
Alirocumab works by inhibiting the
After subcutaneous administration of alirocumab, maximal suppression of free
Chemistry
Alirocumab is a human
It is produced using Chinese hamster ovary cells transfected with recombinant DNA, that are grown in tanks.[3]
History
The importance of PCSK9 as a
The discovery and validation of the target set off a race among pharmaceutical and biotech companies.[14][15]
Alirocumab was discovered by
Phase 1 trial results were reported in 2012 in The New England Journal of Medicine.[17][23] A phase 3 trial of statin intolerant patients called ODYSSEY ran for 65 weeks.[24] Results were presented at the 2014 European Society of Cardiology meeting.[25] A 78-week study of alirocumab in 2341 people taking statins who were at high risk for cardiovascular events and had high LDL cholesterol levels was published in April 2015. This study showed a significant reduction of LDL cholesterol levels in patients taking both Alirocumab and oral statins compared to placebo patients solely taking oral statins.[26] Studies are ongoing to assess the effects of alirocumab in normocholesterolemic individuals.[27]
In July 2014, Regeneron and Sanofi announced that they had purchased a
In July 2015, the FDA approved alirocumab as a second-line treatment to lower
Regeneron and Amgen had each filed for patent protection on their monoclonal antibodies and the companies ended up in patent litigation in the U.S. In March 2016, a district court found that 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.[32] In October, 2017 the US Court of Appeals reversed the ban and ordered a new trial after finding the jury was given improper instructions and evidence was withheld. Regeneron and Sanofi were allowed to continue marketing alirocumab during the appeals process.[33]
The U.S. Food and Drug Administration (FDA) granted approval of Praluent to Regeneron Pharmaceuticals, Inc.[4]
Society and culture
In 2014 as PCSK9 inhibitors approached regulatory approval, market analysts estimated that the overall market for these drugs could be $10B per year, with each of alirocumab and
When the drug was approved in July 2015, the announced price was higher than analysts had predicted: $14,600 a year.
The treatment for people with very high cholesterol that cannot be controlled with diet or statins is apheresis, which is similar to dialysis in that a person visits a clinic each month and his or her blood is mechanically filtered, in this case to remove LDL cholesterol. That treatment costs $8000 per month, or $96,000 per year. The price of alirocumab was determined based in part on making apheresis no longer necessary.[6]
Names
Alirocumab is the international nonproprietary name.[12]
References
- ^ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
- ^ "Health Canada New Drug Authorizations: 2016 Highlights". Health Canada. 14 March 2017. Retrieved 7 April 2024.
- ^ a b c d e f g h i "Praluent- alirocumab injection, solution". DailyMed. Retrieved 1 April 2021.
- ^ a b c d e f "Therapy for patients with severely high cholesterol". U.S. Food and Drug Administration (FDA). 1 March 2021. Retrieved 1 April 2021.
- ^ a b "Praluent EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 1 April 2021.
- ^ a b Kolata G (27 July 2015). "Praluent Looks Cheap to Those With Extreme Cholesterol". New York Times.
- ^ a b c "Press release: FDA approves Praluent to treat certain patients with high cholesterol". U.S. Food and Drug Administration. 24 July 2015.
- ^ a b c Szabo L (24 July 2015). "FDA approves new cholesterol drug - at $14,600 a year". USA Today.
- PMID 30403574.
- S2CID 2201087.
- ^ * "The Evolving Role of PCSK9 Modulation in the Regulation of LDL-Cholesterol". Archived from the original on 2015-05-18. Retrieved 13 May 2015.
- ^ a b "International Nonproprietary Names for Pharmaceutical Substances (INN) List 69" (PDF). WHO Drug Information. 27 (1). World Health Organization. 2013.
- S2CID 28081494.
- S2CID 207325099.
- PMID 25771732.
- ^ "Veloclmmune". Regeneron. 29 December 2015.
- ^ a b BiotechDaily International staff writers (17 April 2012). "LDL-Lowering Monoclonal Antibody Shines in Early Clinical Trials".
- PMID 24037845.
- ISBN 978-1-62703-585-9.
- ^ "Regeneron: Science to Medicine" (PDF). Regeneron. Presentation to Credit Suisse 2013 Antibody Day. 10 May 2013. Archived from the original (PDF) on 2016-03-04.
- ^ Herper M (August 14, 2013). "How Two Guys From Queens Are Changing Drug Discovery". Forbes. United States. Archived from the original on March 16, 2014. Retrieved March 22, 2014.
- S2CID 34214247.
- PMID 22435370.
- PMID 25499937.
- ^ "Huge Decreases in LDL Cholesterol With Alirocumab: ODYSSEY".
- PMID 25773378.
- PMID 31692938.
- ^ Carroll J (July 30, 2014), "Sanofi, Regeneron pay $67M for a shortcut in the blockbuster PCSK9 race with Amgen", FierceBiotech
- ^ Winslow R, Walker J (July 30, 2014), "Drug Firms Buy $67.5 Million Voucher to Speed FDA Review", Wall Street Journal
- ^ Loftus P (1 November 2015). "Drug Makers Buy Pricey Vouchers to Speed Products to Market". Wall Street Journal. Retrieved 19 November 2015.
- ^ Kolata G (29 August 2015). "New Alternatives to Statins Add to a Quandary on Cholesterol". New York Times.
- ^ Feeley J, Bloomfield D, Decker S (5 January 2017). "Amgen Wins Ban on Sanofi's Praluent Cholesterol Drug Sales". Bloomberg News.
- ^ "U.S. court reverses ban on sale of Regeneron, Sanofi cholesterol drug". Reuters. 5 October 2017.
- ^ a b Staton T (7 May 2014). "Payers fret about the next drug doomsday: Pricey PCSK9 cholesterol meds". FiercePharmaMarketing.