Regeneron Pharmaceuticals, Inc.,a leading science-based biopharmaceutical company, announced that in the phase 3 VIVID-DME trial of Eylea (aflibercept) Injection for the treatment of diabetic macular edema (DME), Eylea 2 milligrams (mg) dosed monthly (2Q4) and Eylea 2 mg dosed every two months (after 5 initial monthly injections, 2Q8) showed a sustained improvement from baseline in best corrected visual acuity (BCVA) at week 100 (2 years), compared to laser photocoagulation. The 52-week results (primary analyses) from this study have been previously reported.
Patients in the VIVID-DME trial were randomized to receive either Eylea 2Q4 (n=136), Eylea 2Q8 (n=135), or the comparator treatment of laser photocoagulation (n=132). After two years, patients receiving Eylea 2Q4 had a mean change from baseline in BCVA of 11.4 letters (10.5 letters at 52 weeks, P less than 0.0001 vs. laser). Patients receiving Eylea 2Q8 had a mean change from baseline in BCVA of 9.4 letters (10.7 letters at 52 weeks, P less than 0.0001 vs. laser). Patients in the laser photocoagulation treatment group had a mean change from baseline in BCVA of 0.7 letters (1.2 letters at 52 weeks). Additionally, 31.1 per cent of patients receiving Eylea 2Q8 achieved an increase of greater than or equal to 15 letters, or approximately 3 lines of vision, from baseline (P = 0.0001), and 38.2 percent receiving Eylea 2Q4 achieved an increase of greater than or equal to 15 letters from baseline (P less than 0.0001 vs. laser), compared with 12.1 per cent of patients in the laser control arm achieving similar vision gains.
"These data showed that treatment with Eylea in this trial improved vision and maintained the improvement over two years in patients with diabetic macular edema," said George D. Yancopoulos, M.D., Ph. D., chief scientific officer of Regeneron and president of Regeneron Laboratories.
In this trial, Eylea had a similar overall incidence of adverse events (AEs), ocular serious AEs, and non-ocular serious AEs across the Eylea treatment groups and the laser control group. The most frequent ocular AEs observed in the VIVID-DME trial included conjunctival hemorrhage, cataract, and increased intraocular pressure. The most frequent non-ocular AEs included nasopharyngitis and hypertension. Arterial thromboembolic events as defined by the Anti-Platelet Trialists' Collaboration (non-fatal stroke, non-fatal myocardial infarction, and vascular death) were similar across the treatment groups and the laser control group with events occurring in 8 out of 136 patients in the Eylea 2Q4 group, 5 out of 135 patients in the Eylea 2Q8 group, and 3 out of 133 patients in the laser group. Four out of 136 patients died in the Eylea 2Q4 group, 6 out of 135 patients in the Eylea 2Q8 group, and 1 out of 133 patients in the laser treatment group.
Full two-year data from the VIVID-DME trial will be presented at upcoming medical conferences. Both the VIVID-DME and VISTA-DME trials will continue as planned up to 148 weeks.
Eylea was approved in the United States for the treatment of neovascular (wet) Age-related Macular Degeneration (AMD) in November 2011 and for Macular Edema following Central Retinal Vein Occlusion (CRVO) in September 2012. Eylea has also been approved in the EU and other countries for use in wet AMD and Macular Edema following CRVO. In Europe, the CHMP has given a positive opinion recommending approval for Eylea in the treatment of DME. Regulatory submissions have also been made in Japan, Asia Pacific, Latin America, and the US, for the treatment of DME. In Japan, Eylea has been additionally submitted for approval to regulators for the treatment of choroidal neovascularization secondary to pathologic myopia (mCNV). A regulatory submission has been made in the US and Europe for Eylea for the treatment of macular edema following Branch Retinal Vein Occlusion (BRVO).
Bayer HealthCare and Regeneron are collaborating on the global development of Eylea. Regeneron maintains exclusive rights to Eylea in the United States. Bayer HealthCare licensed the exclusive marketing rights outside the United States, where the companies share equally the profits from sales of Eylea, except for Japan where Regeneron receives a percentage on net sales.
The global phase 3 DME programme consists of three double-masked trials: VIVID-DME, VISTA-DME, and VIVID-EAST-DME, and one open-label, single-arm safety trial in Japanese patients (VIVID-Japan). All three double-masked studies have three treatment arms, where patients are randomized to receive either Eylea 2 mg monthly, Eylea 2 mg every two months (after 5 initial monthly injections), or the comparator treatment of laser photocoagulation. Based on protocol specified criteria, patients were eligible to receive rescue treatment from week 24 onwards. Rescue treatment in the Eylea groups was adjunct laser treatment, and in the laser control group it was Eylea 2 mg. The primary endpoint of all three studies is the mean change in best-corrected visual acuity from baseline, as measured on the Early Treatment Diabetic Retinopathy Scale (ETDRS) eye chart, a standard chart used in research to measure visual acuity. The VIVID-DME, VISTA-DME, and VIVID-EAST-DME studies are ongoing.
Diabetic Macular Edema (DME) is a common complication of Diabetic Retinopathy (DR), a disease affecting the blood vessels of the retina. Clinically significant DME occurs when fluid leaks into the center of the macula, the light-sensitive part of the retina responsible for sharp, direct vision. Fluid in the macula can cause severe vision loss or blindness.
DME is the most frequent cause of blindness in young and mid-aged adults. The treatable population for DME globally is estimated at about 6.2 million people. According to the American Diabetes Association, over 18 million Americans currently suffer from diabetes, and many more are at risk for developing diabetes. The incidence of diabetes is steadily climbing and it is projected that up to seven percent of all patients with diabetes will develop DME during their lifetime.
Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body. In patients with diabetic macular edema (DME), hyperglycemia-induced vascular dysfunction and hypoxia result in elevated intraocular VEGF levels in the eye and resultant blood vessel permeability that leads to macular edema, which can result in vision loss. Eylea is a recombinant fusion protein, consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 and formulated as an iso-osmotic solution for intravitreal administration. Eylea acts as a soluble decoy receptor that binds VEGF-A and placental growth factor (PlGF) and thereby can inhibit the binding and activation of their cognate VEGF receptors.
Regeneron is collaborating with Bayer HealthCare on the global development of Eylea. Eylea is currently marketed for the treatment of wet AMD in over 50 countries outside the US, including Japan and Australia. Bayer HealthCare has received a positive recommendation for approval by the European Committee for Medicinal Products for Human Use (CHMP) for the treatment of visual impairment due to Macular Edema secondary to Central Retinal Vein Occlusion (CRVO).