PANORAMA is the first phase 3 anti–VEGF trial specifically designed to study patients with moderately severe to severe NPDR without DME
PANORAMA Efficacy Outcomes at 24 and 52 Weeks (primary endpoints) and 100 Weeks (prespecified exploratory endpoint*): Proportion of Patients Achieving a ≥2-Step Improvement in ETDRS-DRSS† Score From Baseline1,2,‡
PANORAMA study design: Multicenter, double-masked, controlled clinical study in which patients with moderately severe to severe NPDR (ETDRS-DRSS: 47 or 53) without central-involved DME (CI-DME) (N=402; age range: 25-85 years, with a mean of 56 years) were randomized to receive 1 of 2 EYLEA dosing regimens or sham. Protocol-specified visits occurred every 28±7 days for the first 5 visits, then every 8 weeks (56±7 days). Between week 52 and week 96, patients randomized to one of the EYLEA arms received a different dosing regimen.
The primary efficacy endpoint was the proportion of patients who improved by ≥2 steps on the ETDRS-DRSS from baseline to week 24 in the combined EYLEA groups vs sham and at week 52 in the EYLEA groups individually vs sham. Secondary endpoints included proportion of patients developing proliferative DR (PDR) or anterior segment neovascularization (ASNV); development of CI-DME; and composite endpoint of PDR or ASNV or CI-DME through week 52. All endpoints at week 100 were prespecified exploratory.
VISTA and VIVID study designs: Two randomized, multicenter, double-masked, controlled clinical studies in which patients with DME (N=862; age range: 23-87 years, with a mean of 63 years) were randomized and received 1) EYLEA 2 mg administered every 8 weeks following 5 initial monthly doses; 2) EYLEA 2 mg administered every 4 weeks; or 3) macular laser photocoagulation (control), at baseline and then as needed. Protocol-specified visits occurred every 28 (±7) days.
In both studies, efficacy endpoints included the mean change from baseline in best-corrected visual acuity, as measured by ETDRS letter score, at 52 weeks (primary endpoint) and 100 weeks (secondary endpoint). The percentage of patients with a ≥2-step improvement on the ETDRS-DRSS (an established grading scale for measuring the severity of DR) from baseline at 100 weeks was 38%, 38%, and 16% in VISTA and 32%, 28%, and 7% in VIVID with EYLEA 2 mg every 8 weeks after 5 initial monthly doses, EYLEA 2 mg every 4 weeks, and control, respectively (secondary endpoint).
- anti-VEGF = anti–vascular endothelial growth factor.
- The results of these exploratory endpoints require cautious interpretation, as a multiplicity adjustment has not been applied. Results are descriptive only.
- †Early Treatment Diabetic Retinopathy Study–Diabetic Retinopathy Severity Scale: an established grading scale for measuring the severity of DR.
- ‡Full analysis set.
DR Patients Were Randomly Assigned 1:1:1 to 1 of 3 Treatment Regimens1,2
|Baseline Through Week 96|
|EYLEA 2 mg every 16 weeks||3 monthly injections, followed by 1 injection
after 8 weeks and then 1 injection every 16 weeks
|EYLEA 2 mg every 8 weeks||5 monthly injections, followed by 1 injection every 8 weeks
through week 52. After week 52, patients were switched to a
diﬀerent dosing regimen through week 96
- The recommended dose for EYLEA in DR is 2 mg (0.05 mL) administered by intravitreal injection every 4 weeks (approximately every 28 days, monthly) for the first 5 injections, followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months)1
- Although EYLEA may be dosed as frequently as 2 mg every 4 weeks (approximately every 25 days, monthly), additional efficacy was not demonstrated in most patients when EYLEA was dosed every 4 weeks compared to every 8 weeks. Some patients may need every–4–week (monthly) dosing after the first 20 weeks (5 months)1
Efficacy and safety data of EYLEA in DR are derived from the VISTA, VIVID, and PANORAMA clinical studies1
Power Against Disease Progression
Fewer patients with moderately severe to severe NPDR progressed to proliferative DR (PDR) or anterior segment neovascularization (ASNV) or developed central–involved DME (CI–DME) vs sham through weeks 52 and 100 in the clinical PANORAMA study1,2
Progression to PDR or ASNV or Development of CI–DME Through Weeks 52 and 1001,2,*,†
Start with EYLEA to help stop progression to PDR/ASNV or development of CI-DME1,2
Progression to PDR (defined as ≥2-step worsening on ETDRS-DRSS score)1,2,‡
Through 52 weeks based on reading center score (% patients)1
- EYLEA 2 mg every 8 weeks§: 0% (hazard ratio: 0.00)
- EYLEA 2 mg every 16 weeks§: 1.6% (hazard ratio: 0.11)
- sham: 11.9%
Through 100 weeks based on reading center score (% patients)2
- EYLEA 2 mg every 16 weeks§: 4.5% (hazard ratio: 0.18)
- sham: 20.2%
- Full analysis set.
- †Composite endpoint of developing PDR or ASNV was diagnosed by either the reading center or investigator through week 100.
- ‡Event rate was estimated using the Kaplan-Meier method.
- §EYLEA treatment groups: 3 initial monthly injections, followed by 1 injection after 8 weeks and then 1 injection every 16 weeks; 5 initial monthly injections, followed by 1 injection every 8 weeks in the first year and a different dosing regimen in the second year.
- ¶The results of these exploratory endpoints require cautious interpretation, as a multiplicity adjustment has not been applied.
Anatomic Outcomes at 52 and 100 Weeks2
EYLEA patients had reductions in central retinal thickness2
Mean Change in Central Retinal Thickness, as Measured by OCT,* From Baseline at 52 and 100 Weeks (exploratory endpoints)2,†
The results of these exploratory endpoints require cautious interpretation and could represent chance findings, as a multiplicity adjustment has not been applied.
- Optical coherence tomography.
- †Last observation carried forward; full analysis set.
- §EYLEA treatment groups: 3 initial monthly injections, followed by 1 injection after 8 weeks and then 1 injection every 16 weeks.