Date: 2014-07-18
Type of information: Results
phase: 3
Announcement: results
Company: Bayer Healthcare (Germany) Regeneron Pharmaceuticals (USA)
Product: Eylea® (VEGF Trap-Eye - aflibercept ophthalmic solution)
Action
mechanism: fusion protein/VEGF receptor. 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 these cognate VEGF receptors.
Disease: diabete macular edema (DME)
Therapeutic area: Ophtalmological diseases
Country: Australia, Europe, Japan, Russia, China and other asian countries
Trial
details: The first Phase 3 trial in DME, named VIVID-DME, is being led by Bayer HealthCare and has started in Australia. The trial will also be conducted in Europe and Japan. The VIVID-DME study (VEGF Trap-Eye In Vision Impairment Due to DME) has three study arms. In the first arm, patients will be treated every month with 2 milligrams (mg) of VEGF Trap-Eye. In the second arm, patients will be treated with 2mg of VEGF Trap-Eye every two months after a loading phase of monthly injections. In the third arm, the comparator arm, patients will be treated with macular laser photocoagulation. The primary endpoint is mean change in visual acuity from baseline as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart, a standard chart used in research to measure visual acuity. All patients will be followed for three years. The second study named VISTA-DME (NCT01363440) is led by Regeneron.
The VIVID EAST-DME study (VEGF Trap-Eye In Vision Impairment Due to DME) has three treatment arms. In the first arm, patients will be treated every month with 2 mg of Eylea®. In the second arm, patients will be treated with 2mg of Eylea® every two months after an initial phase of five monthly injections. In the third arm, the comparator arm, patients will be treated with macular laser photocoagulation.
The primary endpoint is mean change in visual acuity from baseline to week 52 as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart, a standard chart used in research to measure visual acuity. All patients will be followed for a maximum of one year. Both studies are fully enrolled.
Latest
news: * On July 18, 2014, Bayer HealthCare announced that in the Phase 3 VIVID-DME trial of aflibercept solution for injection into the eye for the treatment of vision impairment due to diabetic macular edema (DME), aflibercept solution for injection 2 mg, in both treatment groups (dosed monthly or every two months), showed a sustained improvement from baseline in best corrected visual acuity (BCVA) at week 100, compared to laser photocoagulation. Patients in the VIVID-DME trial were randomized to receive either aflibercept solution for injection into the eye every month (n=136), aflibercept solution for injection every two months (after an initial injection every month for five consecutive doses) (n=135), or the comparator treatment of laser photocoagulation (n=132). After two years, patients receiving aflibercept solution for injection every month had a mean gain from baseline in BCVA of 11.4 letters (10.5 letters at 52 weeks; p< 0.0001). This is equivalent to a gain of more than two lines on the ETDRS-eye chart, a standard chart for measuring vision. Patients receiving aflibercept solution for injection every two months had a mean gain from baseline in BCVA of 9.4 letters (10.7 letters at 52 weeks; p<0.0001). 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; p < 0.0001 for each of the aflibercept solution for injection arms vs. laser). Additionally, one third of patients (31.1%) receiving aflibercept solution for injection 2 mg every two months achieved an increase of 15 letters, a gain of three lines from baseline as one of the endpoints compared to the laser treatment group with only twelve percent (12.1%; p<0.0001) achieving a similar gain. In this trial, aflibercept solution for injection was generally well tolerated with a similar overall incidence of adverse events (AEs), ocular serious AEs, and non-ocular serious AEs across the aflibercept solution for injection into the eye treatment groups and the laser treatment group. AEs were typical of those seen in other studies in patients with diabetes receiving intravitreal anti-VEGF therapy. The most frequent ocular AEs in the aflibercept solution for injection groups observed included conjunctival hemorrhage, cataract, and intraocular pressure increased. The most frequent non-ocular AEs in these groups included nasopharyngitis, hypertension, glycosylated haemoglobin increased. 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 group with events occurring in 8 out of 136 patients (5.9%) in the aflibercept solution for injection monthly group, 5 out of 135 patients (3.7%) in the aflibercept solution for injection every two months group, and 3 out of 133 patients (2.3%) in the laser group. Full two-year data from the VIVID-DME trial will be presented at upcoming medical conferences. Both the VIVID-DME and the VISTA-DME trials will continue as planned up to 148 weeks. * On February 10, 2014, Regeneron Pharmaceuticals and Bayer HealthCare have announced that in the Phase 3 VISTA-DME trial of Eylea® (aflibercept) Injection for the treatment of diabetic macular edema, 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, compared to laser photocoagulation. The 52-week results (primary analyses) from this study have been previously reported (see below). Patients in the VISTA-DME trial were randomized to receive either Eylea® 2Q4 (n=155), Eylea® 2Q8 (n=152), or the comparator treatment of laser photocoagulation (n=154). After two years, patients receiving Eylea® 2Q4 had a mean change from baseline in BCVA of 11.5 letters (12.5 letters at 52 weeks). Patients receiving Eylea®2Q8 had a mean change from baseline in BCVA of 11.1 letters (10.7 letters at 52 weeks). Patients in the laser photocoagulation treatment group had a mean change from baseline in BCVA of 0.9 letters (0.2 letters at 52 weeks). "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. "These results are particularly encouraging given that 43 percent of patients in this study had previously received anti-VEGF therapy."In this trial, Eylea® was generally well tolerated with 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. AEs were typical of those seen in other studies in patients with diabetes receiving intravitreal anti-VEGF therapy. The most frequent ocular AEs observed in the VISTA-DME trial included conjunctival hemorrhage, eye pain, and vitreous floaters. The most frequent non-ocular AEs included hypertension, anemia, and urinary tract infection. 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 13 out of 155 patients in the Eylea® 2Q4 group, 11 out of 152 patients in the Eylea® 2Q8 group, and 9 out of 154 patients in the laser group. Eight out of 155 patients died in the Eylea®2Q4 group, 4 out of 152 patients in the Eylea® 2Q8 group, and 3 out of 154 patients in the laser treatment group. Full two-year data from the VISTA-DME trial will be presented at upcoming medical conferences. Two-year data from the similarly designed VIVID-DME trial are expected later in 2014. Both the VISTA-DME and the VIVID-DME trials will continue as planned up to 148 weeks. * On August 6, 2013, Regeneron Pharmaceuticals and Bayer HealthCare have announced that in the Phase 3 VIVID-DME and VISTA-DME trials of Eylea® (aflibercept) Injection for the treatment of diabetic macular edema, Eylea® 2 milligrams (mg) dosed monthly and Eylea® 2 mg dosed every two months (after 5 initial monthly injections) achieved the primary endpoint of a significantly greater improvement in best-corrected visual acuity (BCVA) from baseline compared to laser photocoagulation at 52 weeks. Both Eylea®treatment arms demonstrated similar improvements in BCVA. Based on discussions with the FDA, Regeneron now expects to submit an application for U.S. marketing approval for the treatment of DME in 2013, approximately one year ahead of the previously announced timeline. Bayer Healthcare plans to submit an application for marketing approval for the treatment of DME in Europe in 2013. In the VIVID-DME trial, after one year patients receiving Eylea® 2 mg monthly had a mean change from baseline in BCVA of 10.5 letters (p < 0.0001 compared to laser) and patients receiving Eylea® 2 mg every other month (after 5 initial monthly injections) had a mean change from baseline in BCVA of 10.7 letters (p < 0.0001 compared to laser), compared to patients receiving laser photocoagulation who had a mean change from baseline in BCVA of 1.2 letters. In the VISTA-DME trial, after one year patients receiving Eylea® 2 mg monthly had a mean change from baseline in best-corrected visual acuity (BCVA) of 12.5 letters (p < 0.0001 compared to laser) and patients receiving Eylea® 2 mg every other month (after 5 initial monthly injections) had a mean change from baseline in BCVA of 10.7 letters (p < 0.0001 compared to laser), compared to patients receiving laser photocoagulation who had a mean change from baseline in BCVA of 0.2 letters. In these trials, Eylea® was generally well tolerated with a similar overall incidence of adverse events (AEs), ocular serious AEs, and non-ocular serious AEs across the treatment groups and the laser control group. Arterial thromboembolic events as defined by the Anti-Platelet Trialists' Collaboration (non-fatal stroke, non-fatal myocardial infarction, and vascular death) also occurred at similar rates across the treatment groups and the laser control group. AEs were typical of those seen in other studies in patients with diabetes receiving intravitreal anti-VEGF therapy. The most frequent ocular treatment emergent AEs (TEAEs) observed in the VIVID-DME and VISTA-DME trials included conjunctival hemorrhage, eye pain, and vitreous floaters. The most frequent non-ocular TEAEs included hypertension and nasopharyngitis, which occurred with similar frequency in the treatment groups and the laser control group. * On February 19, 2013, Regeneron Pharmaceuticals and Bayer HealthCare have announced that they have initiated a new Phase 3 trial (named VIVID EAST-DME) to evaluate the efficacy and safety of Eylea® (aflibercept) injection in the treatment of diabetic macular edema (DME) in Russia, China, and other Asian countries. The companies are extending their global development program for Eylea® in DME after promising results in the global Phase 2 DME program. 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. In Japan, Eylea® was approved for use in wet AMD in September 2012. Eylea® was also approved in Europe, Australia, and in several other countries for use in wet AMD last year. * On April 8, 2011, Bayer HealthCare and Regeneron Pharmaceuticals have initiated the first of two Phase 3 clinical trials evaluating the efficacy and safety of VEGF Trap-Eye (aflibercept ophthalmic solution), in the treatment of Diabetic Macular Edema (DME). The companies are extending their development program for VEGF Trap-Eye in DME after promising results in the global Phase 2 DME program.
