Aflibercept with the trade name Eylea is made from a human antibody fragment. Regeneron Pharmaceuticals invented this biopharmaceutical drug for treatment of wet macular degeneration as Eylea injection and also for metastatic colorectal cancer under the trade name Zaltrap. This anti-vascular endothelial growth factor (anti-VEGF) drug reduces the formation of abnormal blood vessels that damage the retina. Eylea cost is about $1,850 per dose. One of the Eylea side effect is burst blood vessel in the eye.
In 2001: Regeneron started clinical testing of Aflibercept for treatment of cancer.
In 2003: Regeneron co-developed Aflibercept for treatment of cancer by signing a major deal with Aventis.
In 2004: Regeneron started testing Aflibercept in proliferative eye diseases.
In 2011: Aflibercept (Eylea) was approved for the treatment of wet age-related macular degeneration by the United States Food and Drug Administration (FDA).
In 2012: Aflibercept (Zaltrap) was approved by the FDA for treating adults with metastatic colorectal cancer resistant to or has progressed following an Oxaliplatin‑containing regimen. It is used in combination with 5-fluorouracil, Folinic acid, and Irinotecan. A new name, ZIV-Aflibercept was selected by FDA as the active ingredient to avoid confusion with Eylea; Aflibercept was approved by the European Medicines Agency (EMA) for treating wet macular degeneration.
In 2016: Cochrane Review examined outcomes of Aflibercept versus ranibizumab injections in over 2400 patients with neovascular AMD, from two randomized controlled trials. Both treatment options caused improvements in visual acuity and morphological outcomes in patients, but authors believed that the Aflibercept treatment regimen has the potential to reduce the risks from injections.
In 2017: the effects of anti-VEGF drugs on diabetic macular edema were studied and after one year, it was found that all three studied treatments have advantages over laser therapy but Aflibercept is significantly favored in all measured efficacy outcomes over ranibizumab and bevacizumab.
Eylea is indicated for adults for the treatment of
- neovascular (wet) age-related macular degeneration (AMD),
- Macular Edema Following Retinal Vein Occlusion (RVO)
- Diabetic Macular Edema (DME)
- Diabetic Retinopathy (DR) in Patients with DME
Eylea side effects
As the common Eylea side effects, we can consider
- burst blood vessel in the eye,
- eye pain or discomfort after the injection,
- watery eyes,
- blurred vision,
- swelling of the eyelids,
- vitreous detachment,
- eye “floaters,”
- increased pressure within the eye, and
- Feeling as if something is in the eye.
AS need new vessels to provide oxygen and nutritive substances needed for facilitating further growth. Aflibercept stops the growth of abnormal blood vessel under the retina (a sensory membrane that lines the inside of the eye) and also stops the leakage of the blood and fluid in the eye(s) that may cause vision loss in people with certain eye conditions.
Aflibercept binds to circulating VEGF (Vascular Endothelial Growth Factor or Vascular Permeability Factor (VPF) (and acts like a “VEGF trap”; activity of the vascular endothelial growth factor subtypes VEGF-A and VEGF-B and placental growth factor (PGF) will be inhibited by this trapping; as a result of it, the growth of new blood vessels in the Choriocapillaris or the tumor, will be stopped respectively. Aflibercept has a unique binding action because it binds to both sides of the VEGF dimer and forming a VEGF Trap. Moreover, Aflibercept is the only drug in its class that binds to PIGF-2.
M710 is a proposed biosimilar to EYLEA® (Aflibercept) injection that announced by Momenta Pharmaceuticals, Inc. and Mylan N.V. They plan to initiate a pivotal clinical trial in patients in 2018.
This trial will be a randomized, double-blind, active-control, multi-center study in patients with diabetic macular edema. Comparing the safety, efficacy, and immunogenicity of M710 with Eylea® is the aim of this study.
Regeneron Pharmaceuticals commercializes Eylea in the US market while Bayer as the main pharmaceutical exporter for hospitals commercializes the drug outside the US market. According to the report of Regeneron, net sales of Eylea (Aflibercept) in the US totaled $953 million in Q3-2017 that showed a 12 percent increase over Q3-2016 revenues of $854 million. And outside the US, net sales of it were $564 million, compared with $471 million in the third quarter of 2016, a 20 percent increase.
Manisha Narasimhan, Ph.D. Regeneron’s head of investor relations stated that about 70 percent of sold Eylea in the US is used for treating wet age-related macular degeneration and about 25 percent goes to treat diabetic macular edema (DME). He believed that DME represents a significant growth opportunity for Eylea because most patients are not currently using an anti-VEGF treatment.
According to the report of Disease Landscape & Forecast Dry and Wet Age-Related Macular Degeneration, it is expected that the total AMD market grows from approximately $4.2 billion in 2016 to more than $7.2 billion in 2026.
It is also expected that biosimilar of Lucentis and Eylea have been introduced during 2016-2026 forecast periods; the launching of these products will impact market growth as the proportion of patients who are treated with branded products decreases.
According to Global Data’s Sales Analytics Database, Regeneron as the main pharmaceutical supply chain for hospitals will maintain its leading position in the ophthalmology market in 2023. This position is due to Eylea (Aflibercept. ( Due to a broad indication of Eylea including AMD, DME and macular edema following retinal vein occlusion, its sales trajectory is likely to continue unabated.
Moreover, Eylea is currently being investigated in diabetic retinopathy without DME, and also in combination with Nesvacumab for wet AMD and DME. Dano Health as a pharmaceutical distributor for hospitals can provide Eylea for hospitals.