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Alirocumab

January 01, 1970

Alirocumab, sold under the brand name Praluent, is a medication used as a second-line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment. It is a human monoclonal antibody that belongs to a novel class of anti-cholesterol drugs, known as PCSK9 inhibitors, and it was the first such agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety.[6]

Alirocumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetProprotein convertase subtilisin/kexin type 9 (PCSK9)
Clinical data
Trade namesPraluent
AHFS/Drugs.comMonograph
MedlinePlusa615035
License data
Pregnancy
category
  • AU: B1
Routes of
administration		Subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
  • 1245916-14-6
DrugBank
  • DB09302
ChemSpider
  • none
UNII
  • PP0SHH6V16
KEGG
  • D10335
Chemical and physical data
FormulaC6472H9996N1736O2032S42
Molar mass145983.80 g·mol−1

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 edit

Alirocumab is used as a second-line treatment to lower LDL cholesterol for adults who have a severe form of hereditary high cholesterol and people with atherosclerosis who require additional lowering of LDL cholesterol when diet and statin treatment have not worked.[3] It is administered by subcutaneous injection.[3] As of July 2015, it is not known whether alirocumab prevents early death from cardiovascular disease or prevents heart attacks;[3] a clinical trial to determine outcomes was ongoing at that time,[7] the results of which were expected in 2017.[8] In November 2018, The New England Journal of Medicine published positive results from a clinical trial with alirocumab. According to the study, alirocumab significantly reduced major adverse cardiovascular events by 15% and it was associated with a 15% lower risk of death from any cause (hazard ratio [HR] 0.85; 95% confidence interval [CI], 0.73 to 0.98).[9]

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 edit

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 edit

Main article: PCSK9

Alirocumab works by inhibiting the PCSK9 protein.[10] PCSK9 binds to the low-density lipoprotein receptor (LDLR) (which takes cholesterol out of circulation), and that binding leads to the receptor being degraded, and less LDL cholesterol being removed from circulation. Inhibiting PCSK9 prevents the receptor from being degraded, and promotes removal of LDL cholesterol from circulation.[11]

After subcutaneous administration of alirocumab, maximal suppression of free PCSK9 occurs within 4 to 8 hours and has an apparent half-life of 17 to 20 days. Inhibition is dose-dependent. The antibody is distributed through the circulation, and it is eliminated at low concentrations by binding to its target, and at higher concentrations through a proteolytic pathway.[3]

Chemistry edit

Alirocumab is a human monoclonal antibody of the IgG1 isotype.[12] It is made of two disulfide-linked human heavy chains, each disulfide-linked to a human light chain. It has an approximate molecular weight of 146 kDa.[3]

It is produced using Chinese hamster ovary cells transfected with recombinant DNA, that are grown in tanks.[3]

History edit

The importance of PCSK9 as a biological target for drug discovery emerged in 2003, when a series of discoveries led to identification of the protein and its gene, its role in causing some cases of familial hypercholesterolaemia when some mutations are present, and its role in causing very low levels of LDL cholesterol when other mutations are present.[13]

The discovery and validation of the target set off a race among pharmaceutical and biotech companies.[14][15]

Alirocumab was discovered by Regeneron Pharmaceuticals using its "VelocImmune" mouse,[16] in which many of the genes coding for antibodies have been replaced with human genes.[17][18][19]: 255–258  In an investor presentation, Regeneron claimed that with their system, it took only about 19 months from when they first immunized mice with PCSK9 until they filed their IND.[20]: Slide 26  Alirocumab was co-developed with Sanofi under a deal made in 2007.[21] Before it received its international nonproprietary name it was known as REGN727 and SAR236553.[22]

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 priority review voucher that BioMarin had won for a recent rare disease drug approval for $67.5 million; the voucher cut four months off the regulatory review time for alirocumab and was part of their strategy to beat Amgen to market with the first approval of a PCSK9 inhibitor.[28][29][30]

In July 2015, the FDA approved alirocumab as a second-line treatment to lower LDL cholesterol for adults who have hereditary high cholesterol and people with atherosclerosis who require additional lowering of LDL cholesterol when diet and statin treatment have not worked.[7] This was the first approval of a PCSK9 inhibitor.[7] The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety.[31]

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 edit

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 Amgen's competing drugs having sales of $3B per year, and other competitors dividing the remaining $4B, based on estimates of an annual price for alirocumab of $10,000 per year.[34] At the same time, pharmacy benefit managers such as Express Scripts and CVS Caremark, while recognizing that the new drugs could help patients who were otherwise left with uncontrolled cholesterol levels, and recognizing that injectable biopharmaceuticals will always be more expensive than pills, and especially more expensive than generic pills, expressed concerns about the burden of the new costs on the health care system.[34]

When the drug was approved in July 2015, the announced price was higher than analysts had predicted: $14,600 a year.[8] Pharmacy benefit managers continued expressing their concerns, as did insurance companies and some doctors, who were especially concerned over the price, in light of the fact that the FDA approval was based on lowering cholesterol alone, and not on better health outcomes, such as fewer heart attacks or longer life.[8]

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 edit

Alirocumab is the international nonproprietary name.[12]

References edit

  1. ^ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  2. ^ "Health Canada New Drug Authorizations: 2016 Highlights". Health Canada. 14 March 2017. Retrieved 7 April 2024.
  3. ^ a b c d e f g h i "Praluent- alirocumab injection, solution". DailyMed. Retrieved 1 April 2021.
  4. ^ 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.
  5. ^ a b "Praluent EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 1 April 2021.
  6. ^ a b Kolata G (27 July 2015). "Praluent Looks Cheap to Those With Extreme Cholesterol". New York Times.
  7. ^ a b c "Press release: FDA approves Praluent to treat certain patients with high cholesterol". U.S. Food and Drug Administration. 24 July 2015.
  8. ^ a b c Szabo L (24 July 2015). "FDA approves new cholesterol drug - at $14,600 a year". USA Today.
  9. ^ Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. (November 2018). "Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome". The New England Journal of Medicine. 379 (22): 2097–2107. doi:10.1056/NEJMoa1801174. hdl:10072/400231. PMID 30403574.
  10. ^ Weinreich M, Frishman WH (2014). "Antihyperlipidemic therapies targeting PCSK9". Cardiology in Review. 22 (3): 140–146. doi:10.1097/CRD.0000000000000014. PMID 24407047. S2CID 2201087.
  11. ^ * . Archived from the original on 2015-05-18. Retrieved 13 May 2015.
  12. ^ a b "International Nonproprietary Names for Pharmaceutical Substances (INN) List 69" (PDF). WHO Drug Information. 27 (1). World Health Organization. 2013.
  13. ^ Hall SS (9 April 2013). "Genetics: A gene of rare effect. A mutation that gives people rock-bottom cholesterol levels has led geneticists to what could be the next blockbuster heart drug". Nature News. 496 (7444): 152–155. doi:10.1038/496152a. PMID 23579660. S2CID 28081494.
  14. ^ Abifadel M, Elbitar S, El Khoury P, Ghaleb Y, Chémaly M, Moussalli ML, et al. (September 2014). "Living the PCSK9 adventure: from the identification of a new gene in familial hypercholesterolemia towards a potential new class of anticholesterol drugs". Current Atherosclerosis Reports. 16 (9): 439. doi:10.1007/s11883-014-0439-8. PMID 25052769. S2CID 207325099.
  15. ^ Desai NR, Sabatine MS (October 2015). "PCSK9 inhibition in patients with hypercholesterolemia". Trends in Cardiovascular Medicine. 25 (7): 567–574. doi:10.1016/j.tcm.2015.01.009. PMID 25771732.
  16. ^ "Veloclmmune". Regeneron. 29 December 2015.
  17. ^ a b BiotechDaily International staff writers (17 April 2012). "LDL-Lowering Monoclonal Antibody Shines in Early Clinical Trials".
  18. ^ Mompó SM, González-Fernández A (2014). "Antigen-specific human monoclonal antibodies from transgenic mice". Human Monoclonal Antibodies. Methods in Molecular Biology (Clifton, N.J.). Vol. 1060. pp. 245–76. doi:10.1007/978-1-62703-586-6_13. ISBN 978-1-62703-585-9. PMID 24037845.
  19. ^ Mompó SM, González-Fernández Á (2014). "Human Monoclonal Antibodies from Transgenic Mice." (PDF). In Steinitz M (ed.). Human Monoclonal Antibodies: Methods and Protocols. New York Heidelberg: Humana Press. ISBN 978-1-62703-585-9.
  20. ^ (PDF). Regeneron. Presentation to Credit Suisse 2013 Antibody Day. 10 May 2013. Archived from the original (PDF) on 2016-03-04.
  21. ^ Herper M (August 14, 2013). "How Two Guys From Queens Are Changing Drug Discovery". Forbes. United States. from the original on March 16, 2014. Retrieved March 22, 2014. 
  22. ^ Sheridan C (December 2013). "Phase 3 data for PCSK9 inhibitor wows". Nature Biotechnology. 31 (12): 1057–1058. doi:10.1038/nbt1213-1057. PMID 24316621. S2CID 34214247.
  23. ^ Stein EA, Mellis S, Yancopoulos GD, Stahl N, Logan D, Smith WB, et al. (March 2012). "Effect of a monoclonal antibody to PCSK9 on LDL cholesterol". The New England Journal of Medicine. 366 (12): 1108–1118. doi:10.1056/NEJMoa1105803. PMID 22435370.
  24. ^ Moriarty PM, Jacobson TA, Bruckert E, Thompson PD, Guyton JR, Baccara-Dinet MT, Gipe D (Nov–Dec 2014). "Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial". Journal of Clinical Lipidology. 8 (6): 554–561. doi:10.1016/j.jacl.2014.09.007. PMID 25499937.
  25. ^ "Huge Decreases in LDL Cholesterol With Alirocumab: ODYSSEY".
  26. ^ Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. (April 2015). "Efficacy and safety of alirocumab in reducing lipids and cardiovascular events" (PDF). The New England Journal of Medicine. 372 (16): 1489–1499. doi:10.1056/NEJMoa1501031. hdl:10447/127416. PMID 25773378.
  27. ^ Kostapanos MS, Cacciottolo PJ, Hubsch A, Pavey H, Hurlock J, Maki-Petaja K, et al. (24 October 2019). "Investigating the lowest threshold of vascular benefits from LDL cholesterol lowering with a PCSK9 mAb inhibitor (alirocumab) in healthy volunteers - a mechanistic physiological study (INTENSITY-LOW): protocol and study rationale". Journal of Drug Assessment. 8 (1): 167–174. doi:10.1080/21556660.2019.1677673. PMC 6818119. PMID 31692938.
  28. ^ Carroll J (July 30, 2014), "Sanofi, Regeneron pay $67M for a shortcut in the blockbuster PCSK9 race with Amgen", FierceBiotech
  29. ^ Winslow R, Walker J (July 30, 2014), "Drug Firms Buy $67.5 Million Voucher to Speed FDA Review", Wall Street Journal
  30. ^ Loftus P (1 November 2015). "Drug Makers Buy Pricey Vouchers to Speed Products to Market". Wall Street Journal. Retrieved 19 November 2015.
  31. ^ Kolata G (29 August 2015). "New Alternatives to Statins Add to a Quandary on Cholesterol". New York Times.
  32. ^ Feeley J, Bloomfield D, Decker S (5 January 2017). "Amgen Wins Ban on Sanofi's Praluent Cholesterol Drug Sales". Bloomberg News.
  33. ^ "U.S. court reverses ban on sale of Regeneron, Sanofi cholesterol drug". Reuters. 5 October 2017.
  34. ^ a b Staton T (7 May 2014). "Payers fret about the next drug doomsday: Pricey PCSK9 cholesterol meds". FiercePharmaMarketing.

January 01, 1970
alirocumab, sold, under, brand, name, praluent, medication, used, second, line, treatment, high, cholesterol, adults, whose, cholesterol, controlled, diet, statin, treatment, human, monoclonal, antibody, that, belongs, novel, class, anti, cholesterol, drugs, k. Alirocumab sold under the brand name Praluent is a medication used as a second line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment It is a human monoclonal antibody that belongs to a novel class of anti cholesterol drugs known as PCSK9 inhibitors and it was the first such agent to receive FDA approval The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety 6 AlirocumabMonoclonal antibodyTypeWhole antibodySourceHumanTargetProprotein convertase subtilisin kexin type 9 PCSK9 Clinical dataTrade namesPraluentAHFS Drugs comMonographMedlinePlusa615035License dataUS DailyMed AlirocumabPregnancycategoryAU B1Routes ofadministrationSubcutaneousATC codeC10AX14 WHO Legal statusLegal statusAU S4 Prescription only 1 CA only 2 UK POM Prescription only US only 3 4 EU Rx only 5 In general Prescription only IdentifiersCAS Number1245916 14 6DrugBankDB09302ChemSpidernoneUNIIPP0SHH6V16KEGGD10335Chemical and physical dataFormulaC 6472H 9996N 1736O 2032S 42Molar mass145983 80 g mol 1 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 Contents 1 Medical uses 2 Side effects 3 Pharmacology 4 Chemistry 5 History 6 Society and culture 6 1 Names 7 ReferencesMedical uses editAlirocumab is used as a second line treatment to lower LDL cholesterol for adults who have a severe form of hereditary high cholesterol and people with atherosclerosis who require additional lowering of LDL cholesterol when diet and statin treatment have not worked 3 It is administered by subcutaneous injection 3 As of July 2015 it is not known whether alirocumab prevents early death from cardiovascular disease or prevents heart attacks 3 a clinical trial to determine outcomes was ongoing at that time 7 the results of which were expected in 2017 8 In November 2018 The New England Journal of Medicine published positive results from a clinical trial with alirocumab According to the study alirocumab significantly reduced major adverse cardiovascular events by 15 and it was associated with a 15 lower risk of death from any cause hazard ratio HR 0 85 95 confidence interval CI 0 73 to 0 98 9 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 editSide 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 editMain article PCSK9 Alirocumab works by inhibiting the PCSK9 protein 10 PCSK9 binds to the low density lipoprotein receptor LDLR which takes cholesterol out of circulation and that binding leads to the receptor being degraded and less LDL cholesterol being removed from circulation Inhibiting PCSK9 prevents the receptor from being degraded and promotes removal of LDL cholesterol from circulation 11 After subcutaneous administration of alirocumab maximal suppression of free PCSK9 occurs within 4 to 8 hours and has an apparent half life of 17 to 20 days Inhibition is dose dependent The antibody is distributed through the circulation and it is eliminated at low concentrations by binding to its target and at higher concentrations through a proteolytic pathway 3 Chemistry editAlirocumab is a human monoclonal antibody of the IgG1 isotype 12 It is made of two disulfide linked human heavy chains each disulfide linked to a human light chain It has an approximate molecular weight of 146 kDa 3 It is produced using Chinese hamster ovary cells transfected with recombinant DNA that are grown in tanks 3 History editThe importance of PCSK9 as a biological target for drug discovery emerged in 2003 when a series of discoveries led to identification of the protein and its gene its role in causing some cases of familial hypercholesterolaemia when some mutations are present and its role in causing very low levels of LDL cholesterol when other mutations are present 13 The discovery and validation of the target set off a race among pharmaceutical and biotech companies 14 15 Alirocumab was discovered by Regeneron Pharmaceuticals using its VelocImmune mouse 16 in which many of the genes coding for antibodies have been replaced with human genes 17 18 19 255 258 In an investor presentation Regeneron claimed that with their system it took only about 19 months from when they first immunized mice with PCSK9 until they filed their IND 20 Slide 26 Alirocumab was co developed with Sanofi under a deal made in 2007 21 Before it received its international nonproprietary name it was known as REGN727 and SAR236553 22 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 priority review voucher that BioMarin had won for a recent rare disease drug approval for 67 5 million the voucher cut four months off the regulatory review time for alirocumab and was part of their strategy to beat Amgen to market with the first approval of a PCSK9 inhibitor 28 29 30 In July 2015 the FDA approved alirocumab as a second line treatment to lower LDL cholesterol for adults who have hereditary high cholesterol and people with atherosclerosis who require additional lowering of LDL cholesterol when diet and statin treatment have not worked 7 This was the first approval of a PCSK9 inhibitor 7 The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety 31 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 editIn 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 Amgen s competing drugs having sales of 3B per year and other competitors dividing the remaining 4B based on estimates of an annual price for alirocumab of 10 000 per year 34 At the same time pharmacy benefit managers such as Express Scripts and CVS Caremark while recognizing that the new drugs could help patients who were otherwise left with uncontrolled cholesterol levels and recognizing that injectable biopharmaceuticals will always be more expensive than pills and especially more expensive than generic pills expressed concerns about the burden of the new costs on the health care system 34 When the drug was approved in July 2015 the announced price was higher than analysts had predicted 14 600 a year 8 Pharmacy benefit managers continued expressing their concerns as did insurance companies and some doctors who were especially concerned over the price in light of the fact that the FDA approval was based on lowering cholesterol alone and not on better health outcomes such as fewer heart attacks or longer life 8 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 edit Alirocumab is the international nonproprietary name 12 References edit 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 Schwartz GG Steg PG Szarek M Bhatt DL Bittner VA Diaz R et al November 2018 Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome The New England Journal of Medicine 379 22 2097 2107 doi 10 1056 NEJMoa1801174 hdl 10072 400231 PMID 30403574 Weinreich M Frishman WH 2014 Antihyperlipidemic therapies targeting PCSK9 Cardiology in Review 22 3 140 146 doi 10 1097 CRD 0000000000000014 PMID 24407047 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 Hall SS 9 April 2013 Genetics A gene of rare effect A mutation that gives people rock bottom cholesterol levels has led geneticists to what could be the next blockbuster heart drug Nature News 496 7444 152 155 doi 10 1038 496152a PMID 23579660 S2CID 28081494 Abifadel M Elbitar S El Khoury P Ghaleb Y Chemaly M Moussalli ML et al September 2014 Living the PCSK9 adventure from the identification of a new gene in familial hypercholesterolemia towards a potential new class of anticholesterol drugs Current Atherosclerosis Reports 16 9 439 doi 10 1007 s11883 014 0439 8 PMID 25052769 S2CID 207325099 Desai NR Sabatine MS October 2015 PCSK9 inhibition in patients with hypercholesterolemia Trends in Cardiovascular Medicine 25 7 567 574 doi 10 1016 j tcm 2015 01 009 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 Mompo SM Gonzalez Fernandez A 2014 Antigen specific human monoclonal antibodies from transgenic mice Human Monoclonal Antibodies Methods in Molecular Biology Clifton N J Vol 1060 pp 245 76 doi 10 1007 978 1 62703 586 6 13 ISBN 978 1 62703 585 9 PMID 24037845 Mompo SM Gonzalez Fernandez A 2014 Human Monoclonal Antibodies from Transgenic Mice PDF In Steinitz M ed Human Monoclonal Antibodies Methods and Protocols New York Heidelberg Humana Press 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 nbsp Sheridan C December 2013 Phase 3 data for PCSK9 inhibitor wows Nature Biotechnology 31 12 1057 1058 doi 10 1038 nbt1213 1057 PMID 24316621 S2CID 34214247 Stein EA Mellis S Yancopoulos GD Stahl N Logan D Smith WB et al March 2012 Effect of a monoclonal antibody to PCSK9 on LDL cholesterol The New England Journal of Medicine 366 12 1108 1118 doi 10 1056 NEJMoa1105803 PMID 22435370 Moriarty PM Jacobson TA Bruckert E Thompson PD Guyton JR Baccara Dinet MT Gipe D Nov Dec 2014 Efficacy and safety of alirocumab a monoclonal antibody to PCSK9 in statin intolerant patients design and rationale of ODYSSEY ALTERNATIVE a randomized phase 3 trial Journal of Clinical Lipidology 8 6 554 561 doi 10 1016 j jacl 2014 09 007 PMID 25499937 Huge Decreases in LDL Cholesterol With Alirocumab ODYSSEY Robinson JG Farnier M Krempf M Bergeron J Luc G Averna M et al April 2015 Efficacy and safety of alirocumab in reducing lipids and cardiovascular events PDF The New England Journal of Medicine 372 16 1489 1499 doi 10 1056 NEJMoa1501031 hdl 10447 127416 PMID 25773378 Kostapanos MS Cacciottolo PJ Hubsch A Pavey H Hurlock J Maki Petaja K et al 24 October 2019 Investigating the lowest threshold of vascular benefits from LDL cholesterol lowering with a PCSK9 mAb inhibitor alirocumab in healthy volunteers a mechanistic physiological study INTENSITY LOW protocol and study rationale Journal of Drug Assessment 8 1 167 174 doi 10 1080 21556660 2019 1677673 PMC 6818119 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 Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Alirocumab amp oldid 1217670433, wikipedia, wiki, book, books, library,

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