Aflibercept

Last updated

Aflibercept
Clinical data
Trade names Eylea, Zaltrap
Other namesziv-aflibercept
Biosimilars aflibercept-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
MedlinePlus a612004
License data
Pregnancy
category
  • AU:D [9]
  • Not recommended
Routes of
administration 		Intravenous, intravitreal injection
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C4318H6788N1164O1304S32
Molar mass 96898.57 g·mol−1
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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

Contents

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

Medical uses

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

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

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

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

Mechanism of action

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

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

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

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

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]

Economics

In March 2015, aflibercept was one of a group of drugs delisted from the UK Cancer Drugs Fund. [40] In 2017, injections of aflibercept (HCPCS code J0178) were responsible for the most billing to Medicare Part B, at US$2.36 billion. [41]

Research

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] [42]

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. [43]

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. [44]

Related Research Articles

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Macular edema occurs when fluid and protein deposits collect on or under the macula of the eye and causes it to thicken and swell (edema). The swelling may distort a person's central vision, because the macula holds tightly packed cones that provide sharp, clear, central vision to enable a person to see detail, form, and color that is directly in the centre of the field of view.

<span class="mw-page-title-main">Macular degeneration</span> Vision loss due to damage to the macula of the eye

Macular degeneration, also known as age-related macular degeneration, is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, some people experience a gradual worsening of vision that may affect one or both eyes. While it does not result in complete blindness, loss of central vision can make it hard to recognize faces, drive, read, or perform other activities of daily life. Visual hallucinations may also occur.

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<span class="mw-page-title-main">Intravitreal administration</span>

Intravitreal administration is a route of administration of a drug, or other substance, in which the substance is delivered into the vitreous humor of the eye. "Intravitreal" literally means "inside an eye". Intravitreal injections were first introduced in 1911 when Ohm gave an injection of air into the vitreous humor to repair a detached retina. In the mid-1940s, intravitreal injections became a standard way to administer drugs to treat endophthalmitis and cytomegalovirus retinitis.

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<span class="mw-page-title-main">Pegaptanib</span> Drug to treat macular degeneration

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References

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  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "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. 1 2 3 4 "PAVBLU" (PDF).
  4. 1 2 3 "Yesafili (aflibercept-jbvf) injection, for intravitreal use" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 19 August 2024.
  5. 1 2 3 4 "AHZANTIVE" (PDF).
  6. 1 2 3 "Opuviz (aflibercept-yszy) injection, for intravitreal use" (PDF). Archived (PDF) from the original on 21 May 2024. Retrieved 21 May 2024.
  7. 1 2 "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.
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  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. 1 2 3 4 5 6 "Eylea- aflibercept injection, solution". DailyMed. 12 August 2019. Archived from the original on 25 March 2021. Retrieved 13 August 2020.
  12. 1 2 3 4 5 6 "Zaltrap- ziv-aflibercept solution, concentrate". DailyMed. 10 June 2020. Archived from the original on 4 August 2020. Retrieved 13 August 2020.
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  15. 1 2 3 4 5 "Zaltrap EPAR". European Medicines Agency (EMA). 12 November 2019. Archived from the original on 11 November 2020. Retrieved 12 March 2020.
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  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.
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  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.
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  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. ↑ "BLA APPROVAL" (PDF).
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  44. ↑ 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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