The Phase 3 PANORAMA Study of Intravitreal Aflibercept for Moderately Severe to Severe NonProliferative Diabetic Retinopathy

Patrick Higgins

Abstract

Purpose: Diabetic retinopathy (DR), caused by microvascular damage to the retina, is a common manifestation of diabetes mellitus, and its course can be altered with anti-vascular endothelial growth factor therapy. Our goal was to evaluate the efficacy and safety of intravitreal aflibercept injection (IAI) compared to sham treatment in the improvement of moderately severe to severe non-proliferative DR (NPDR).

Methods: PANORAMA is a double-masked, randomized, phase 3 trial. Patients ?18 years of age with diabetes mellitus could be eligible if they had (a) moderately severe to severe NPDR (Diabetic Retinopathy Severity Scale [DRSS] levels 47 or 53) without diabetic macular edema, and (b) baseline best corrected visual acuity (BCVA) ?69 letters (approximately ?20/40). Patients were randomized equally to 1 of 3 arms: IAI 2 mg q8 weeks after 5 monthly doses (2q8), IAI 2 mg q16 weeks after 3 monthly doses and 1 8-week interval (2q16), or sham injections through week 48. The primary endpoint is the proportion of patients demonstrating ?2-step improvement in DRSS score at week 24 in the combined IAI groups.

Results: PANORAMA enrolled 402 patients from 5 countries (United States, Japan, Germany, Hungary, and United Kingdom). At baseline, mean age was 55.7 years, 44.0% were women, mean HbA1c was 8.5%, and mean diabetes duration was 14.4 years. Mean baseline BCVA was 82.7 and 82.3 letters in the sham and combined IAI groups, respectively. Corresponding central retinal thickness was 249.4 and 246.4 µm, respectively. The majority of the patients presented with DRSS level of 47 (versus 53): 74.4% and 75.5%, respectively. IAI-treated patients received a mean of 4.4 treatments through week 24. Overall, 58.0% (156/269) of IAI treated patients experienced a ?2-step improvement in DRSS score at week 24 compared with 6.0% (8/133) of sham treated patients (P<0.0001). No new safety signals were observed.

Conclusion: These findings at week 24 demonstrate that IAI improved diabetic retinopathy severity in patients with moderately severe to severe NPDR and suggest that IAI may reverse disease progression in these patients.

Details

Year: 2018

Program Number: 180008

Resource Type: Scientific Program

Author Affiliation: Retina Center of New Jersey

Co-Authors: n/a

Co-Author Affiliation: n/a

Room: Room 303