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Aflibercept

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Aflibercept
Clinical data
Trade namesEylea, Zaltrap
Other namesziv-aflibercept
Biosimilarsaflibercept-abzv,[1][2] aflibercept-ayyh,[3][2] aflibercept-jbvf,[4][2] aflibercept-mrbb,[5][2] aflibercept-yszy,[6][2] Ahzantive,[5][2] Enzeevu,[1][2] Opuviz,[6][2] Pavblu,[3][2] Yesafili[4][7][8][2]
AHFS/Drugs.com
MedlinePlusa612004
License data
Pregnancy
category
  • AU: D[9]
  • Not recommended
Routes of
administration		Intravenous, intravitreal injection
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: ℞-only[10]
  • UK: POM (Prescription only)
  • US: ℞-only[11][12][13]"Eylea HD- aflibercept injection, solution". DailyMed. 18 August 2023. Archived from the original on 29 August 2023. Retrieved 28 August 2023.</ref>
  • EU: Rx-only[14][15]
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC4318H6788N1164O1304S32
Molar mass96898.57 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Aflibercept, sold under the brand names Eylea and Zaltrap among others, is a medication used to treat wet macular degeneration and metastatic colorectal cancer.[14][15] It was developed by Regeneron Pharmaceuticals.

It is an inhibitor of vascular endothelial growth factor (VEGF).[16][17]

Medical uses

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Aflibercept (Eylea) is indicated for the treatment of people with neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, and retinopathy of prematurity.[11]

Aflibercept (Zaltrap), in combination with fluorouracil, leucovorin, and irinotecan (known as FOLFIRI), is indicated for the treatment of people with metastatic colorectal cancer that is resistant to, or has progressed following, an oxaliplatin-containing regimen.[12][15]

It is used for the treatment of wet macular degeneration and is administered as an intravitreal injection, that is, into the eye.[11] For cancer treatment, it is given intravenously in combination with fluorouracil, leucovorin, and irinotecan.[12]

In July 2014, aflibercept (Eylea) was approved for the treatment of people with visual impairment due to diabetic macular edema[18] In May 2019, the US FDA expanded the indication for aflibercept to include all stages of diabetic retinopathy.[19]

In February 2023, the US FDA approved aflibercept (Eylea) as a treatment for retinopathy of prematurity.[20]

Contraindications

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Aflibercept (Eylea) is contraindicated in people with infections or active inflammations of or near the eye,[11] while aflibercept (Zaltrap) has no contraindications.[12]

Adverse effects

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Common adverse effects of the eye formulation include conjunctival hemorrhage, eye pain, cataract, vitreous detachment, floaters, and ocular hypertension.[11]

Aflibercept (Zaltrap) has adverse effects typical of anti-cancer drugs, such as reduced blood cell count (leukopenia, neutropenia, thrombocytopenia), gastrointestinal disorders like diarrhea and abdominal pain, and fatigue. Another common effect is hypertension (increased blood pressure).[12]

Interactions

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No interactions are described for either formulation.[11][12]

Mechanism of action

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In wet macular degeneration, abnormal blood vessels grow in the choriocapillaris, a layer of capillaries in the eye, leading to blood and protein leakage below the macula.

Aflibercept (Zaltrap) binds to circulating VEGFs and acts like a "VEGF trap".[21] It thereby inhibits the activity of the vascular endothelial growth factor subtypes VEGF-A and VEGF-B, as well as to placental growth factor (PGF), inhibiting the growth of new blood vessels in the choriocapillaris or the tumour, respectively.[22] The aim of the cancer treatment, so to speak, is to starve the tumor.

Composition

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Aflibercept is a recombinant fusion protein consisting of vascular endothelial growth factor (VEGF)-binding portions from the extracellular domains of human VEGF receptors 1 and 2, that are fused to the Fc portion of the human IgG1 immunoglobulin.[23]

History

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Regeneron commenced clinical testing of aflibercept in cancer in 2001.[24] In 2003, Regeneron signed a major deal with Aventis to develop aflibercept in the field of cancer.[25] In 2004 Regeneron started testing the compound, locally delivered, in proliferative eye diseases,[24] and in 2006 Regeneron and Bayer signed an agreement to develop the eye indications.[26]

Society and culture

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[edit]

In November 2011, the US Food and Drug Administration (FDA) approved aflibercept for the treatment of wet macular degeneration.[27][28]

In August 2012, the US FDA approved aflibercept (Zaltrap) for use in combination with 5-fluorouracil, folinic acid and irinotecan to treat adults with metastatic colorectal cancer that is resistant to, or has progressed following, an oxaliplatin‑containing regimen.[29][23][30][31] To avoid confusion with the version that is injected into the eye, the FDA assigned a new name, ziv-aflibercept, to the active ingredient.[32]

In November 2012, the European Medicines Agency (EMA) approved aflibercept (Eylea) for the treatment of wet macular degeneration.[14][33]

In February 2013, the European Medicines Agency (EMA) approved aflibercept (Zaltrap) for the treatment of adults with metastatic colorectal cancer for whom treatment based on oxaliplatin has not worked or the cancer got worse.[15][34] Aflibercept (Zaltrap) is used with irinotecan, 5-fluorouracil, and folinic acid.[15]

In August 2023, the FDA approved aflibercept (Eylea) for the treatment of wet age-related macular degeneration, diabetic macular edema, and diabetic retinopathy.[35]

Biosimilars

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Yesafili was approved for medical use in the European Union in September 2023.[7]

In May 2024, aflibercept-jbvf (Yesafili)[4] and aflibercept-yszy (Opuviz)[6] were approved for medical use in the United States.[36][2]

Aflibercept-mrbb (Ahzantive) was approved for medical use in the United States in June 2024.[5][37][2] It is a biosimilar to Eylea.[5]

In August 2024, aflibercept-abzv (Enzeevu) was approved for medical use in the United States.[1][38][2] It is a biosimilar to Eylea.[1]

In August 2024, aflibercept-ayyh (Pavblu) was approved for medical use in the United States.[3][39][2] It is a biosimilar to Eylea.[3]

In September 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Opuviz, intended for the treatment of neovascular (wet) age-related macular degeneration, visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO or central RVO), visual impairment due to diabetic macular edema (DME) and visual impairment due to myopic choroidal neovascularization (myopic CNV).[40] The applicant for this medicinal product is Samsung Bioepis NL B.V.[40] Opuviz is a biosimilar medicinal product that is highly similar to the reference product Eylea (aflibercept), which was authorized in the EU in November 2012.[40]

In September 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Afqlir, intended for the treatment of neovascular (wet) age-related macular degeneration, visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO or central RVO), visual impairment due to diabetic macular edema (DME) and visual impairment due to myopic choroidal neovascularization (myopic CNV).[41] The applicant for this medicinal product is Sandoz GmbH.[41] Afqlir is a biosimilar medicinal product that is highly similar to the reference product Eylea (aflibercept), which was authorized in the EU in November 2012.[41] Afqlir was authorized for use in the EU in November 2024.[42][43]

In November 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Ahzantive, intended for the treatment of neovascular (wet) age-related macular degeneration, visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO or central RVO), visual impairment due to diabetic macular edema (DME) and visual impairment due to myopic choroidal neovascularisation (myopic CNV).[44] The applicant for this medicinal product is Klinge Biopharma GmbH.[44] Ahzantive is a biosimilar medicinal product that is highly similar to the reference product Eylea (aflibercept), which was authorized in the EU in November 2012.[44][45]

In November 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Baiama, intended for the treatment of neovascular (wet) age-related macular degeneration, visual impairment due to macular edema secondary to retinal vein occlusion (branch RVO or central RVO), visual impairment due to diabetic macular edema (DME) and visual impairment due to myopic choroidal neovascularisation (myopic CNV).[46] The applicant for this medicinal product is Formycon AG.[46] Baiama is a biosimilar medicinal product that is highly similar to the reference product Eylea (aflibercept), which was authorized in the EU in November 2012.[46][45]

Economics

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In March 2015, aflibercept was one of a group of drugs delisted from the UK Cancer Drugs Fund.[47] In 2017, injections of aflibercept (HCPCS code J0178) were responsible for the most billing to Medicare Part B, at US$2.36 billion.[48]

Research

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In March 2011, aflibercept failed its primary endpoint of overall survival in the Vital phase III trial for second-line treatment of locally advanced or metastatic non-small cell lung cancer, although it improved the secondary endpoint of progression-free survival.[22][49]

In April 2011, aflibercept improved its primary endpoint of overall survival in the Velour phase III clinical trial for second-line treatment for metastatic colorectal cancer.[22]

Aflibercept was also in a phase III trial for hormone-refractory metastatic prostate cancer as of April 2011.[22]

A 2016 Cochrane Review examined outcomes comparing aflibercept versus ranibizumab injections in over 2400 people with neovascular AMD, from two randomized controlled trials. Both treatment options yielded similar improvements in visual acuity and morphological outcomes, though the authors note that the aflibercept treatment regimen has the potential to reduce treatment burden and risks from frequent injections.[50]

A 2017 review update studying the effects of anti-VEGF drugs on diabetic macular edema found that while all three studied treatments have advantages over laser therapy, there was moderate evidence that aflibercept is significantly favored in all measured efficacy outcomes over ranibizumab and bevacizumab, after one year, longer term advantages were unclear.[51]

References

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  1. ^ a b c d "Enzeevu (aflibercept-abzv) injection, for intravitreal use" (PDF). Archived (PDF) from the original on 8 September 2024. Retrieved 26 August 2024.
  2. ^ a b c d e f g h i j k l m n "Biosimilar Drug Information". U.S. Food and Drug Administration (FDA). 26 August 2024. Archived from the original on 28 August 2021. Retrieved 26 August 2024.
  3. ^ a b c d "Pavblu- aflibercept-ayyh injection, solution". DailyMed. 28 October 2024. Retrieved 11 November 2024.
  4. ^ a b c "Yesafili (aflibercept-jbvf) injection, for intravitreal use" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 19 August 2024.
  5. ^ a b c d "Ahzantive" (PDF). Archived (PDF) from the original on 5 October 2024. Retrieved 26 August 2024.
  6. ^ a b c "Opuviz (aflibercept-yszy) injection, for intravitreal use" (PDF). Archived (PDF) from the original on 21 May 2024. Retrieved 21 May 2024.
  7. ^ a b "Yesafili EPAR". European Medicines Agency. 15 September 2023. Archived from the original on 17 February 2024. Retrieved 21 May 2024.
  8. ^ "Yesafili Product information". Union Register of medicinal products. 19 September 2023. Archived from the original on 2 October 2023. Retrieved 2 October 2023.
  9. ^ "Ziv-aflibercept (Zaltrap) Use During Pregnancy". Drugs.com. 25 December 2019. Archived from the original on 29 November 2020. Retrieved 12 March 2020.
  10. ^ "Regulatory Decision Summary for Eylea HD". Drug and Health Products Portal. 2 February 2024. Archived from the original on 2 April 2024. Retrieved 2 April 2024.
  11. ^ a b c d e f "Eylea- aflibercept injection, solution". DailyMed. 12 August 2019. Archived from the original on 25 March 2021. Retrieved 13 August 2020.
  12. ^ a b c d e f "Zaltrap- ziv-aflibercept solution, concentrate". DailyMed. 10 June 2020. Archived from the original on 4 August 2020. Retrieved 13 August 2020.
  13. ^ Cite error: The named reference Eylea HD FDA label was invoked but never defined (see the help page).
  14. ^ a b c "Eylea EPAR". European Medicines Agency (EMA). 9 July 2019. Archived from the original on 9 November 2020. Retrieved 12 March 2020.
  15. ^ a b c d e "Zaltrap EPAR". European Medicines Agency (EMA). 12 November 2019. Archived from the original on 11 November 2020. Retrieved 12 March 2020.
  16. ^ Fraser HM, Wilson H, Silvestri A, Morris KD, Wiegand SJ (September 2008). "The role of vascular endothelial growth factor and estradiol in the regulation of endometrial angiogenesis and cell proliferation in the marmoset". Endocrinology. 149 (9): 4413–20. doi:10.1210/en.2008-0325. PMID 18499749. Archived from the original on 8 December 2019. Retrieved 3 July 2008.
  17. ^ Duncan WC, van den Driesche S, Fraser HM (July 2008). "Inhibition of vascular endothelial growth factor in the primate ovary up-regulates hypoxia-inducible factor-1alpha in the follicle and corpus luteum". Endocrinology. 149 (7): 3313–20. doi:10.1210/en.2007-1649. PMID 18388198.
  18. ^ "Eylea (aflibercept) FDA Approval History". Drugs.com. 18 November 2011. Archived from the original on 19 June 2024. Retrieved 26 August 2024.
  19. ^ "FDA Approves Eylea (aflibercept) Injection for Diabetic Retinopathy". Regeneron Pharmaceuticals Inc. (Press release). 13 May 2019. Archived from the original on 14 May 2019. Retrieved 28 June 2023.
  20. ^ "Eylea (aflibercept) Injection Approved as the First Pharmacologic Treatment for Preterm Infants with Retinopathy of Prematurity (ROP) by the FDA". Regeneron Pharmaceuticals Inc. (Press release). 8 February 2023. Archived from the original on 28 June 2023. Retrieved 28 June 2023.
  21. ^ "Aflibercept Approved for Colorectal Cancer in Europe". 7 February 2013. Archived from the original on 10 February 2013.
  22. ^ a b c d "Regeneron and Sanofi-Aventis Report Positive Phase III mCRC Trial Data". 27 April 2011. Archived from the original on 2 February 2012.
  23. ^ a b "Ziv-Aflibercept". U.S. Food and Drug Administration (FDA). 3 August 2012. Archived from the original on 16 October 2013. Retrieved 16 October 2013.
  24. ^ a b "Our History - A 25 year commitment to repeated innovation". www.regeneron.com. 1988. Archived from the original on 17 May 2017. Retrieved 7 May 2018.
  25. ^ Hoffmann C (8 September 2003). "Aventis inks deal with Regeneron for collaboration on cancer therapy". firstwordpharma. Archived from the original on 14 April 2014.
  26. ^ "Bayer HealthCare Signs On to Help Develop Regeneron's VEGF Trap-Eye". GEN - Genetic Engineering and Biotechnology News. 19 October 2006. Retrieved 17 September 2024.
  27. ^ "Drug Approval Package: Eylea (aflibercept) NDA #125387". U.S. Food and Drug Administration (FDA). 18 November 2011. Archived from the original on 17 October 2023. Retrieved 21 May 2024.
  28. ^ Gever J (19 November 2011). "FDA Approves Eylea for Macular Degeneration". MedpageToday.com. Archived from the original on 28 May 2013. Retrieved 16 October 2013.
  29. ^ "Drug Approval Package: Zaltrap (ziv-aflibercept) NDA #125418". U.S. Food and Drug Administration (FDA). 6 September 2012. Archived from the original on 26 September 2022. Retrieved 21 May 2024.
  30. ^ "2012 Notifications". U.S. Food and Drug Administration (FDA). 17 December 2012. Archived from the original on 26 December 2019. Retrieved 21 May 2024.
  31. ^ "U.S. FDA Approves Zaltrap (ziv-aflibercept) After Priority Review for Previously Treated Metastatic Colorectal Cancer" (Press release). Sanofi and Regeneron. 3 August 2012. Archived from the original on 21 May 2024. Retrieved 21 May 2024 – via PR Newswire.
  32. ^ Serebrov M. "GPhA: Common Name is Key to Biosimilar Competition". BioWorld. Archived from the original on 13 December 2013.
  33. ^ "Aflibercept Injection Approved for the Treatment of Wet Age-Related Macular Degeneration in Europe". Amd-fruehdiagnose.de. Archived from the original on 25 November 2013. Retrieved 16 October 2013.
  34. ^ "Zaltrap : EPAR - Summary for the public" (PDF). Archived (PDF) from the original on 16 October 2013. Retrieved 1 July 2013.
  35. ^ "Eylea HD (aflibercept) Injection 8 mg Approved by FDA for Treatment of Wet Age-related Macular Degeneration (wAMD), Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR)" (Press release). Regeneron Pharmaceuticals. 18 August 2023. Archived from the original on 26 August 2023. Retrieved 26 August 2024 – via GlobeNewswire.
  36. ^ "FDA approves first interchangeable biosimilars to Eylea to treat macular degeneration and other eye conditions". U.S. Food and Drug Administration (FDA) (Press release). 20 May 2024. Archived from the original on 21 May 2024. Retrieved 21 May 2024.
  37. ^ "Ahzantive Biologic License Application Approval" (PDF). Archived (PDF) from the original on 8 September 2024. Retrieved 26 August 2024.
  38. ^ "Enzeevu Biologic License Application Approval" (PDF). Archived (PDF) from the original on 5 October 2024. Retrieved 26 August 2024.
  39. ^ "Pavblu Biologic License Application Approval" (PDF). Archived (PDF) from the original on 8 September 2024. Retrieved 26 August 2024.
  40. ^ a b c "Pavblu EPAR". European Medicines Agency (EMA). 19 September 2024. Archived from the original on 21 September 2024. Retrieved 21 September 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  41. ^ a b c "Afqlir EPAR". European Medicines Agency (EMA). 19 September 2024. Archived from the original on 21 September 2024. Retrieved 21 September 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  42. ^ "Afqlir PI". Union Register of medicinal products. 14 November 2024. Retrieved 20 November 2024.
  43. ^ "Sandoz receives European Commission approval for Afqlir (aflibercept), further strengthening leading biosimilar portfolio". Yahoo News.
  44. ^ a b c "Ahzantive EPAR". European Medicines Agency (EMA). 14 November 2024. Retrieved 16 November 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  45. ^ a b "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 11-14 November 2024". European Medicines Agency (EMA) (Press release). 15 November 2024. Retrieved 16 November 2024.
  46. ^ a b c "Baiama EPAR". European Medicines Agency (EMA). 14 November 2024. Retrieved 16 November 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  47. ^ "Cancer: Drugs:Written question - HL3340". UK Parliament. 19 November 2015. Archived from the original on 2 April 2018.
  48. ^ "Physician/Supplier National Data" (PDF). Centers for Medicare & Medicaid Services. Archived (PDF) from the original on 17 August 2018. Retrieved 11 June 2019.
  49. ^ "Regeneron and Sanofi-Aventis Cancer Drug Misses Phase III Primary Endpoint but Meets Secondary Targets". 11 March 2011. Archived from the original on 6 April 2012.
  50. ^ Sarwar S, Clearfield E, Soliman MK, Sadiq MA, Baldwin AJ, Hanout M, et al. (February 2016). "Aflibercept for neovascular age-related macular degeneration". The Cochrane Database of Systematic Reviews. 2016 (2): CD011346. doi:10.1002/14651858.CD011346.pub2. PMC 5030844. PMID 26857947.
  51. ^ Virgili G, Curran K, Lucenteforte E, Peto T, Parravano M, et al. (Cochrane Eyes and Vision Group) (June 2023). "Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis". The Cochrane Database of Systematic Reviews. 2023 (6): CD007419. doi:10.1002/14651858.CD007419.pub7. PMC 10294542. PMID 38275741.
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