Aflibercept, sold under the brand names Eylea and Zaltrap among others, is a medication used to treat
wet macular degeneration and metastatic
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...
.
It was developed by
Regeneron Pharmaceuticals.
It is an inhibitor of
vascular endothelial growth factor
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...
(VEGF).
Aflibercept is a recombinant fusion protein consisting of the extracellular domains of human VEGF receptor 1 and 2 fused to the Fc portion of human IgG1.
By acting as a soluble decoy for the natural VEGF receptors, aflibercept inhibits their activation, thereby reducing angiogenesis.
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.
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.
It is used for the treatment of wet macular degeneration and is administered as an
intravitreal injection, that is, into the eye.
For cancer treatment, it is given
intravenous
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
ly in combination with fluorouracil, leucovorin, and irinotecan.
In July 2014, aflibercept (Eylea) was approved for the treatment of people with visual impairment due to diabetic macular edema In May 2019, the US FDA expanded the indication for aflibercept to include all stages of
diabetic retinopathy.
In February 2023, the US FDA approved aflibercept (Eylea) as a treatment for retinopathy of prematurity.
Contraindications
Aflibercept (Eylea) is contraindicated in people with infections or active
inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
s of or near the eye,
while aflibercept (Zaltrap) has no contraindications.
Adverse effects
Common adverse effects of the eye formulation include conjunctival
hemorrhage
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...
, eye pain, cataract,
vitreous detachment,
floaters, and
ocular hypertension.
Aflibercept (Zaltrap) has adverse effects typical of anti-cancer drugs, such as reduced blood cell count (
leukopenia
Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections.
Signs and symptoms
Symptoms may include:
* s ...
,
neutropenia,
thrombocytopenia), gastrointestinal disorders like diarrhea and abdominal pain, and fatigue. Another common effect is
hypertension
Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...
(increased blood pressure).
Interactions
No interactions are described for either formulation.
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". It thereby inhibits the activity of the vascular endothelial growth factor subtypes
VEGF-A and
VEGF-B, as well as to
placental growth factor
Placental growth factor (PlGF) is a protein that in humans is encoded by the ''PGF'' gene.
Placental growth factor is a member of the VEGF (vascular endothelial growth factor) sub-family - a key molecule in angiogenesis and vasculogenesis, in ...
(PGF), inhibiting the growth of new blood vessels in the choriocapillaris or the tumour, respectively.
[ 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
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors ...
(VEGF)-binding portions from the extracellular domains of human VEGF receptor
Receptor may refer to:
* Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
s 1 and 2, that are fused to the Fc portion of the human IgG1 immunoglobulin.
History
Regeneron commenced clinical testing of aflibercept in cancer in 2001.[ and in 2006 Regeneron and Bayer signed an agreement to develop the eye indications.
]
Society and culture
Legal status
In November 2011, the US Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA) approved aflibercept for the treatment of wet macular degeneration.
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
Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication (platinum-based antineoplastic class) used to treat colorectal cancer. It is given by intravenous, infusion into a vein.
Common side effects include paresth ...
‑containing regimen.European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
(EMA) authorized aflibercept (Eylea) for the treatment of wet macular degeneration.European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
(EMA) authorized aflibercept (Zaltrap) for the treatment of adults with metastatic colorectal cancer for whom treatment based on oxaliplatin
Oxaliplatin, sold under the brand name Eloxatin among others, is a cancer medication (platinum-based antineoplastic class) used to treat colorectal cancer. It is given by intravenous, infusion into a vein.
Common side effects include paresth ...
has not worked or the cancer got worse.
Biosimilars
Yesafili was authorized for medical use in the European Union in September 2023.European Medicines Agency
The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...
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).[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
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).[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.] Afqlir was authorized for use in the EU in November 2024.
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).[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.][ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.][ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.]
In January 2025, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Pavblu, intended for the treatment of neovascular (wet) age-related macular degeneration (AMD), 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).[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.] Pavblu is a biosimilar medicinal product.[ Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.] Skojoy is a biosimilar medicinal product.
Economics
In March 2015, aflibercept was one of a group of drugs delisted from the UK Cancer Drugs Fund. In 2017, injections of aflibercept ( HCPCS code J0178) were responsible for the most billing to Medicare Part B, at .
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.[
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
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...
.[
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.]
References
External links
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{{Authority control
Angiogenesis inhibitors
Drugs developed by Bayer
Engineered proteins
Ophthalmology drugs
Sanofi