NIH- sponsored trial finds Eylea reduced vision threatening complications by 68% after two years in diabetic retinopathy patients .- Regeneron + Bayer

Regeneron announced JAMA Ophthalmology has published initial results from the National Institutes of Health-sponsored Protocol W trial assessing Eylea (aflibercept) Injection in patients with moderate to severe non-proliferative diabetic retinopathy (NPDR), without center-involved diabetic macular edema (CI-DME). At two years, the primary outcome of the trial showed a 68% reduced risk of developing vision-threatening complications (either proliferative diabetic retinopathy [PDR] or CI-DME with vision loss) in patients who received the Eylea every-16-weeks dosing regimen. In comparison, patients receiving sham injections were almost five times more likely to experience disease progression requiring Eylea rescue therapy. Although at the two-year time point of Protocol W, preventive Eylea treatment did not confer a significant difference in visual acuity versus delayed Eylea treatment following vision-threatening complications (i.e., sham), a recent Regeneron follow-up analysis in the similarly designed PANORAMA trial found that delaying Eylea treatment resulted in three times as many patients suffering prolonged vision loss, compared to those receiving preventive Eylea treatment, during a two-year period. A similar analysis has not yet been conducted for Protocol W. "Blindness is one of the most feared consequences of diabetic retinopathy, and we thank the National Eye Institute and the DRCR Retina Network for conducting a well-controlled trial that provides useful information to guide treatment in these patients," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "Protocol W confirms the landmark results of the similarly-designed PANORAMA trial, underscoring the importance of early and regular diabetic retinopathy treatment and the ability of Eylea to substantially reduce vision-threatening complications and improve disease severity. Importantly, these results were obtained with an every-16-weeks Eylea dosing regimen, confirming the efficacy with Eylea seen in the PANORAMA trial." In Protocol W, patients were randomly assigned to receive either Eylea (2 mg, n=200 eyes) every 16 weeks, after receiving four initial doses at weeks 0, 4, 8 and 16, or sham (n=199 eyes). Patients had excellent vision when they entered the trial, with more than three-quarters of eyes having 20/20 visual acuity or better (78% Eylea 81% sham). Rescue therapy (primarily Eylea) was administered to patients if they developed either PDR or CI-DME. Compared to sham, Eylea-treated patients were: i. 68% less likely to develop CI-DME with vision loss or PDR, the primary outcome measure at two years (p<0.001). ii. the cumulative probability of developing pdr or ci-dme with vision loss was 16 with eylea versus 44 with sham. elyea patients were 66 less likely to develop pdr p><0.001) and 64 less likely to develop ci-dme with vision loss p="0.002).iii." three times more likely to experience at least a two-step improvement in their dr severity score drss. in total 69 45 eylea patients experienced at least a two-step improvement versus 22 14 of those in the sham group adjusted odds ratio or: 5.91 p><0.001). iv. five times less likely to require rescue therapy with eylea due to pdr or dme 4 eylea 19 sham. other rescue treatments were panretinal photocoagulation prp><1% eylea 2 sham vitrectomy for pdr><1% eylea><1% sham and focal grid laser treatment for dme 0 eylea 2 sham. in the retrospective panorama analysis of vision outcomes over two years three times more patients in the sham group suffered from prolonged vision loss range: 6 weeks to 6 months compared to the eylea every-16-weeks dosing group 12 of 135 eylea 38 of 133 sham. results by loss of letters were as follows as measured by the early treatment diabetic retinopathy study etdrs chart: i. greater than 5 letter loss: 9 eylea versus 29 sham nominal p><0.0001. ii. greater than 10 letter loss: 5 eylea versus 14 sham nominal p="0.0212." iii. greater than 15 letter loss: 3 eylea versus 8 sham nominal p="0.0672." no new safety signals were identified in protocol w consistent with the known safety profile of eylea. ocular adverse events aes included endophthalmitis n="3" eylea n="0" sham. the rate of any cardiovascular cerebrovascular aes was not significantly different among the treatment groups 9 of patients treated with eylea in one eye 9 of patients treated with sham in one eye and 8 of patients treated with both eylea one eye and sham other eye. diabetic retinopathy is the leading cause of blindness among working adults. however vision loss is often preventable if proactive measures are taken by patients and their doctors said allen c. ho m.d. attending surgeon and director of retina research at wills eye hospital in philadelphia pa. past trials have shown that early systemic and ocular intervention in diabetic eye disease can lead to sustained improvements in visual acuity over the long term while undertreatment can put patients vision at risk. the latest data from protocol w and panorama support this treatment philosophy by showing that an every-16-week eylea regimen helped patients avoid vision-threatening complications and prolonged periods of vision loss over two years. i look forward to seeing additional protocol w vision outcomes at four years. eylea is the only vascular endothelial growth factor vegf inhibitor that is fda approved with two dosing intervals for dr allowing doctors to customize treatment. in dr eylea may be dosed every eight weeks following five initial monthly injections or every four weeks. eylea is not approved for 16-week dosing as was studied in protocol w. see- march 30 2021-prevention of severe nonproliferative diabetic retinopathy progression with more at stake than visual acuity- jennifer i. lim md. jama ophthalmol. published online march 30 2021. doi:10.1001 jamaophthalmol.2021.0625.>