Regeneron Pharmaceuticals announced positive two-year results from the Phase 3 PANORAMA trial evaluating EYLEA® (aflibercept) Injection 2 mg (0.05 mL) in patients with moderately severe to severe non-proliferative diabetic retinopathy (NPDR).
The two-year pre-specified exploratory data demonstrate that untreated moderately severe and severe NPDR can lead to vision-threatening events, which includes vision-threatening complications (VTCs; proliferative diabetic retinopathy or anterior segment neovascularization) and center-involved diabetic macular edema (CI-DME). Based on a Kaplan-Meier analysis, more than half (58%) of patients in the untreated sham arm developed a VTC or CI-DME within two years of entering the trial, while EYLEA treatment was shown to reduce the likelihood of these vision-threatening events by at least 75% (nominal p<0.0001).
"These data reinforce that regular EYLEA treatment can be highly effective at reducing the risk of new vision-threatening events among patients with moderately severe to severe non-proliferative diabetic retinopathy," said Charles C. Wykoff, M.D., Ph.D., PANORAMA investigator, retina surgeon and ophthalmologist with Retina Consultants of Houston. "The PANORAMA trial shows that more than half of all untreated patients developed vision-threatening events over two years, underscoring the value of treating patients proactively and regularly."
The two-year results also showed a greater benefit for EYLEA patients treated at regular intervals compared to patients who received EYLEA treatment less frequently. Per the protocol, the group of trial patients who received EYLEA every 8 weeks in the first year were switched to receive it when their doctor determined they needed it (called pro re nata, or PRN) in the second year (i.e., the 8-week/PRN group). The proportion of these patients with a >2-step improvement from baseline in Diabetic Retinopathy Severity Scale (DRSS) scores decreased in the second year (80% improvement at 52 weeks and 50% at 100 weeks).* By comparison, in patients who continued to receive EYLEA every 16 weeks (i.e., the 16-week group), the >2-step DRSS scores remained consistent (65% at 52 weeks vs. 62% at 100 weeks).* In the second year, patients received an average of 1.8 injections in the 8-week/PRN group (out of a possible 6); a review of data from the independent reading center of investigator PRN decisions suggests that some of these patients may have been under-dosed based on the protocol rules of the trial. Patients in the 16-week group received 2.6 injections (out of a possible 3) in the second year.
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During the 2-year PANORAMA trial, adverse events were consistent with the known profile of EYLEA. Serious ocular adverse events in the study eye occurred in 2% and 0% of the EYLEA 8-week/PRN and 16-week groups, respectively, and 2% of patients in the sham group. Ocular inflammation occurred in 2% and 1% of patients in the EYLEA treatment groups, respectively, and 1% of patients in the sham group. Anti-platelet trialists' collaboration (APTC)-defined arterial thromboembolic treatment emergent events occurred in 3% and 6% of patients in the EYLEA treatment groups, respectively, and 5% of patients in the sham group.
The U.S. Food and Drug Administration (FDA) approval of EYLEA to treat diabetic retinopathy was based on six-month and one-year results from PANORAMA, a randomized, multi-center, controlled Phase 3 trial that enrolled 402 patients and was designed to investigate EYLEA for the improvement of moderately severe to severe NPDR without DME, compared to sham injection. PANORAMA is the first prospective trial to study whether vascular endothelial growth factor (VEGF) inhibition can also help prevent worsening disease in patients with NPDR without DME.
Approximately eight million people live with diabetic retinopathy, a disease characterized by microvascular damage to the blood vessels in the retina often caused by poor blood sugar control in people with diabetes. The disease generally starts as NPDR and often has no warning signs or symptoms. NPDR may progress to a stage of the disease in which abnormal blood vessels grow onto the surface of the retina and potentially cause severe, vision-threatening complications such as proliferative diabetic retinopathy and anterior segment neovascularization.
DME can occur at any stage of diabetic retinopathy as the blood vessels in the retina become increasingly fragile and leak fluid, potentially causing visual impairment. In the U.S., approximately 1.5 million adults are diagnosed with DME, while approximately 3.5 million people have diabetic retinopathy without DME.
EYLEA® (aflibercept) Injection is a vascular endothelial growth factor (VEGF) inhibitor formulated as an injection for the eye. It is designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels (vascular permeability) in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in angiogenesis. In the U.S., EYLEA is the number one prescribed FDA-approved anti-VEGF treatment across its approved indications and is supported by a robust body of research that includes seven pivotal Phase 3 trials.