On February 13, 2018, Bayer announced that the China Food and Drug Administration (CFDA) had approved Eylea®(Aflibercept Intravitreal Injection Solution) is indicated for the treatment of diabetic macular edema (DME) in adults. Prior to this, the Center for Drug Evaluation (CDE) of the China Food and Drug Administration had included the marketing application for this drug in the priority review program in May 2017. Aflibercept Intravitreal Injection Solution is currently the only anti-VEGF agent approved in China for the treatment of diabetic macular edema.
Mr. Jiang Wei, Executive Vice President of Bayer Pharmaceuticals and President of China and the Asia-Pacific Region, stated: “Bayer is committed to high-quality innovation and aims to benefit a broad patient population by providing innovative medicines and services. Eylea”®Approved by the CFDA for the treatment of diabetic macular edema (DME), this represents highly welcome news for the growing number of patients suffering from vision impairment due to DME, providing an innovative therapeutic option for those with severe ocular conditions. For Bayer, this also marks a significant milestone, demonstrating its substantial progress in the field of ophthalmology and underscoring its commitment to innovation and patient care in this area.
“China has over 100 million patients with diabetes, and diabetic retinopathy (DR) is one of its serious complications, representing a major cause of vision loss among the working-age population. The ‘Clinical Diagnosis and Treatment Guidelines for Diabetic Retinopathy in China,’ released in 2014, pointed out that as the prevalence of DR increases year by year, the rate of blindness also rises annually. Strengthening screening, referral, and timely management of DR has become an urgent priority.” Xu Xun, Deputy Chairman of the Ophthalmology Branch of the Chinese Medical Association and Head of the Fundus Disease Group, stated: “As a form of diabetic retinopathy that severely impairs vision, diabetic macular edema (DME) is currently treated mainly with laser therapy, anti-VEGF agents, and corticosteroids. Anti-VEGF therapy has become one of the first-line treatments for diabetic macular edema in Europe and the United States.”
Eylea® is the world’s first fully human fusion protein, a soluble decoy receptor that binds to VEGF-A and PlGF, thereby inhibiting the binding and activation of endogenous VEGF receptors by VEGF-A and PlGF.
For the treatment of diabetic macular edema, the recommended dose of aflibercept intravitreal injection solution is 2 mg, administered once monthly for the first 5 months, followed by injections every two months (8 weeks). After 12 months of treatment, the dosing interval may be extended based on visual acuity and anatomical outcomes.
Currently, aflibercept intravitreal injection solution has been approved for five indications in more than 100 countries worldwide, primarily for the treatment of vision impairment caused by retinal diseases, including diabetic macular edema (DME), neovascular (wet) age-related macular degeneration (AMD), retinal vein occlusion (RVO, including branch retinal vein occlusion [BRVO] and central retinal vein occlusion [CRVO]), and vision impairment due to myopic choroidal neovascularization (myopic CNV). Since its market launch, global usage of aflibercept intravitreal injection solution has exceeded 16 million doses.
Regarding the VISTA, VIVID, and VIVID-EAST Clinical Trials
Large-scale, Phase III randomized controlled clinical trials for diabetic macular edema—VISTA, VIVID, and VIVID-EAST—have been conducted with intravitreal aflibercept injection in multiple countries and regions, including the United States, Europe, and Asia. Among these, VIVID-EAST was conducted in Asian countries and enrolled 378 patients, with more than 80% of them from China.
These three studies all compared the efficacy and safety of intravitreal aflibercept injection solution 2 mg administered monthly, every 2 months (after an initial 5 consecutive monthly injections), or laser photocoagulation treatment (treatment at baseline followed by as-needed treatment) for DME. In these studies, based on the primary endpoint: the mean change in best-corrected visual acuity (BCVA) at one year, it was found that intravitreal aflibercept injection solution administered every 2 months resulted in similar visual improvement to monthly administration, both significantly superior to the laser treatment control group; patients in the intravitreal aflibercept injection solution treatment groups showed an average improvement of approximately two lines on the visual acuity chart in reading ability, while there was almost no change in the control group.
Not only was vision significantly improved, but the study also found that more than one-third of patients in the aflibercept intravitreal injection solution treatment group achieved an improvement of more than two steps on the Diabetic Retinopathy Severity Scale (DRSS). This effect was more pronounced in the Asian population, where over 60% of patients with diabetic macular edema (DME) achieved a DRSS improvement of more than two steps, all significantly higher than those in the control group. These findings also suggest that treatment with aflibercept intravitreal injection solution can reduce disease severity. In terms of safety, the overall incidence rates of adverse events (AEs), serious ocular adverse events, and serious non-ocular adverse events were similar between the Eylea® treatment group and the laser control group.
Professor Chen Youxin, Principal Investigator of the VIVID-EAST study and from the Department of Ophthalmology at Peking Union Medical College Hospital, stated, “In the treatment of patients with diabetic macular edema (DME), intravitreal aflibercept injection has demonstrated favorable efficacy and safety in both Chinese and Asian populations. In addition to improving visual acuity in patients with diabetic macular edema, intravitreal aflibercept injection also reduces the severity of retinopathy in these patients, making it an effective therapeutic option for diabetic macular edema.”
Regarding Guideline Recommendations
One-year results from the Protocol-T randomized controlled trial, initiated by the National Institutes of Health (NIH), evaluating treatments for diabetic macular edema (DME), demonstrated that in patients with a baseline visual acuity ≤ 0.4 (20/50), improvements in both visual acuity and retinal anatomical structure were significantly superior to those achieved with ranibizumab (p = 0.003) and bevacizumab (p < 0.001).
Professor Li Xiaoxin, a renowned Chinese expert in fundus diseases and former Chairman of the Ophthalmology Branch of the Chinese Medical Association, pointed out: Based on these authoritative studies, guidelines for the treatment of diabetic macular edema (DME) issued by multiple domestic and international academic organizations all indicate that anti-VEGF agents are an important and effective therapeutic option for DME. Furthermore, based on the results of the Protocol T study, patients with poorer baseline visual acuity may achieve better improvements in both visual acuity and anatomical structure when treated with Eylea®.
About Diabetic Macular Edema (DME)
Vision impairment caused by diabetic macular edema (DME) is estimated to affect 3–4% of patients with diabetes, making DME the most common cause of blindness among young and middle-aged adults in developed countries. As the prevalence of diabetes continues to rise, the number of individuals affected by DME is also expected to increase.
Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR) are common microvascular complications of diabetes. DR is a disease affecting the retinal blood vessels. Clinically significant DME occurs when fluid leaks into the center of the macula. Macular edema can lead to decreased central vision, and in severe cases, it may result in profound visual impairment or blindness.
About VEGF and EYLEA® (aflibercept intravitreal injection solution)
Vascular Endothelial Growth Factor (VEGF) is a cytokine naturally produced in the human body. In healthy individuals, it promotes angiogenesis, thereby supporting the growth of tissues and organs. It is also associated with abnormal intraocular neovascularization, increasing vascular permeability and leading to retinal edema.
Eylea®The active ingredient is aflibercept. It is a fusion protein produced by Chinese hamster ovary (CHO) K1 cells through recombinant DNA technology. This fusion protein is a homodimeric glycoprotein formed by fusing the extracellular domains of human vascular endothelial growth factor receptors (VEGFR), specifically the Ig2 domain of VEGFR1 and the Ig3 domain of VEGFR2, with the Fc domain of human IgG1. This product is for intravitreal injection only. Aflibercept acts as a soluble decoy receptor that binds to VEGF-A and placental growth factor (PLGF), thereby inhibiting the binding and activation of these factors with native VEGF receptors.