One-Year Results From Positive Phase 3 Eylea Trial In Diabetic Retinopathy Presented At Angiogenesis Symposium
Trial showed that early intervention with EYLEA improved diabetic retinopathy severity and prevented serious vision-threatening complications
EYLEA diabetic retinopathy sBLA target action date of?May 13, 2019
Regeneron Pharmaceuticals, Inc.?(NASDAQ:?REGN) today?announced that positive detailed one-year results?from the Phase 3 PANORAMA trial evaluating EYLEA??(aflibercept) Injection in patients with moderately severe to severe non-proliferative diabetic retinopathy (NPDR)?were presented?for the first time at the Angiogenesis, Exudation, and Degeneration 2019 symposium.
The trial confirmed that moderately severe and severe non-proliferative diabetic retinopathy is not a benign condition, with patients at high risk of rapidly progressing to vision-threatening events. In untreated patients with severe NPDR, 53% developed these events at one year. Most importantly, EYLEA treatment prevented approximately 74% of these complications.
Key one-year data presented at the meeting are summarized below:
DRSS=Diabetic Retinopathy Severity Scale
a?p<0.0001 versus sham
b?Vision-threatening events defined as vision-threatening complications (VTC; proliferative diabetic retinopathy or anterior segment neovascularization) or central-involved diabetic macular edema (CI-DME)
c?Nominal p=0.0019 versus sham
d?Nominal p<0.0001 versus sham
Topline one-year results from PANORAMA were previously?reported?in?October 2018.
"PANORAMA provides high-quality data to inform treatment of NPDR without DME, as it is the first prospective trial involving these high-risk patients since the landmark ETDRS trial of the 1980s when laser was the only treatment option," said?Charles C. Wykoff, M.D., Ph.D., PANORAMA investigator, retina surgeon and ophthalmologist with?Retina Consultants?of?Houston. "Without treatment, a large percentage of patients in the trial developed proliferative disease and CI-DME in the first year. EYLEA treatment reduced the risk of these events by approximately 74% compared to sham injection, underscoring the potential importance of early EYLEA anti-VEGF therapy. This efficacy was seen even with an every 16-week treatment regimen after loading doses, a management approach that may realistically be achieved in the real world."
Adverse events were consistent with the known profile of EYLEA. Serious ocular treatment-emergent adverse events in the study eye occurred in 0 and 1 patients in the EYLEA treatment groups and 1 patient in the sham injection group. Ocular inflammation occurred in 1 patient in each EYLEA treatment group and 0 patients in the sham injection group. Anti-Platelet Trialists' Collaboration (APTC)-defined arterial thromboembolic treatment-emergent events occurred in 4 and 2 patients in the EYLEA treatment groups and 5 patients in the sham injection group.
A supplemental Biologics License Application (sBLA) for EYLEA in diabetic retinopathy has been accepted for review by the U.S.?FDA?with a target action date of?May 13, 2019.
The safety and efficacy of EYLEA in diabetic retinopathy in patients without DME have not been fully evaluated by any regulatory authority.
About the PANORAMA trial
PANORAMA is an ongoing, pivotal, double-masked, randomized, two-year trial that enrolled 402 patients and is designed to investigate EYLEA for the improvement of moderately severe to severe NPDR in patients without DME, compared to sham injections. Details on trial design include:
Sham Control(N=133) | EYLEA Every 16 Weeks (N=135) | EYLEA Every 8 Weeks (N=134) | |
Primary Endpoint | |||
% of patients with =2-step improvement on DRSS score from baselinea | 15% | 65%a | 80%a |
Impact on Vision-Threatening Events | |||
Patients who developed a vision-threatening eventb | 41% | 10%a | 11%a |
Subgroup with severe NPDR at baseline (n=100) | 53% | 15%c | 15%c |
Subgroup with moderately severe NPDR at baseline (n=302) | 36% | 8%d | 10%d |
- Three treatment arms?? An observational sham injection group and two EYLEA treatment groups. EYLEA was dosed every 8 weeks (following five initial monthly doses) or every 16 weeks (following three initial monthly doses and one 8-week interval).
- Primary endpoint?? The primary endpoint was the proportion of patients who experienced a two-step or greater improvement in the DRSS from baseline for the combined EYLEA treatment groups at week 24, and for each EYLEA treatment group separately (every 8-week group and every 16-week group) at week 52. The DRSS is a systematic grading scale to assess the severity of diabetic retinopathy based on photographs of the retina following a dilated eye exam.
- Secondary endpoints?? These include assessment of whether EYLEA reduced VTCs (defined as proliferative diabetic retinopathy and anterior segment neovascularization) or development of CI-DME, as well as its impact on other anatomic effects, visual acuity improvement, and safety.
- EYLEA??(aflibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA.
- Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. Intraocular inflammation has been reported with the use of EYLEA.
- Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately.
- There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with EYLEA compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the EYLEA group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with EYLEA compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies.
- Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with EYLEA including endophthalmitis and retinal detachment.
- The most common adverse reactions (=5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased.