Slide 1: Baseline Factors Associated With No Improvement in DRSS Score in Sham Patients From PANORAMA
Baseline Factors Associated With No Improvement in Diabetic Retinopathy Severity Scale Score in Sham Patients From PANORAMA Over 2 Years Anita Barikian, MD on behalf of the PANORAMA study investigators East Florida Eye Institute, Stuart, Florida Presented at the Association for Research in Vision an
Slide 2: PANORAMA Study Design
PANORAMA Study Design Phase 3, double-masked, randomized study of IAI efficacy and safety in patients with moderately severe to severe NPDR (DRSS level 47 and 53) N=4022 IAI 2q16° n=135 _-.— ru Week 24 Primary endpoint: Proportion of patients improving 22 steps on DRSS All IAI combined versus sham K
Slide 3: Proportion of Patients with ≥2-Step DRSS Improvement from Baseline
Proportion of Patients with 22-Step DRSS Improvement from Baseline Sham (n=133) ‘IAI 2q16 (n=135) —_ IAI 298 (n=134) = 100 5 8 79.9 5 80 4 = 62.7 85.2 62.28 2 60 va fo) < 40 2 5 20 Q fe} = o O 24 52 100 24 52 100 24 52 100° Week In PANORAMA, 15% and 13% of patients in the sham group had a 22-step DR
Slide 4: Background
Background * Some patients with DR may improve in severity spontaneously without intervention’ * Baseline factors predicting which patients are likely to improve or not improve in DR severity may help physicians to prioritize appropriate patients for closer monitoring and earlier treatment + In PANO
Slide 5: Baseline factors were evaluated for association with no DRSS score improvement
Baseline factors were evaluated for association with no DRSS score improvement (worsening/no change) as well as 21-step DRSS improvement The baseline factors evaluated which were considered to be clinically relevant were patient characteristics, medical history, clinical and ocular characteristics,
Slide 6: Baseline factors evaluated
Age BMI Ethnicity Diabetes duration Diabetes type Hypertension Lipid disorder Microvascular Diabetic nephropathy Peripheral neuropathy Antihypertensives Lipid-lowering agents Insulin Hemoglobin A1c Race Sex BCVA CST Center subfield sector volume DRSS score Macrovascular Coronary artery disease Cereb
Slide 7: Proportion of patients by DRSS response at Week 52
Proportion of patients, % 100 - 80 4 60 4 FAS, full analysis set; LOCF, last observation carried forward. 52.6 Worsening or no change in DRSS (n=70) ATA 21-step DRSS improvement (n=63)
Slide 8: Baseline Characteristics by DRSS Response at Week 52 in Sham Patients
FAS, LOCF. ETDRS, Early Treatment Diabetic Retinopathy Study; HbA1c, hemoglobin A1c; NP, nonperfusion; SD, standard deviation. Baseline Characteristics by DRSS Response at Week 52 in Sham Patients 21-step DRSS improvement (n=63) Age, mean (SD), years 54.4 (11.1) 57.5 (9.2) Female, n (%) 36 (51.4) 28
Slide 9: Univariate analysis at Week 52
Leakage area (per 5-mm? increase) Leakage distance to fovea : (per 1-mm increase) Lipid-lowering —eo medication use (yes vs no) Odds ratio (95% Cl) 0.00 0.50 1.00 1.50 Odds ratio (95% Cl) Favors 21-step DRSS improvement +—___ LOCE. Inferential results were derived from a logistic regression model ad
Slide 10: Multivariable analysis at Week 52
Leakage area (per 5-mm? increase) Lipid-lowering medication use (yes vs no) Odds ratio (95% Cl) 0.00 0.50 1.00 1.50 Odds ratio (95% Cl) 2.00 1.28 (1.08, 1.51) 0.32 (0.14, 0.73) Favors 21-step DRSS improvement Favors no DRSS score improvement — ———— Nominal P-value 0.0040 0.0068 LOCF. The odds ratio
Slide 11: Proportion of patients by DRSS response at Week 100
FAS, LOCF. Proportion of patients, % 100 - 80 4 60 4 60.2 Worsening or no change in DRSS (n=80) 39.8 21-step DRSS improvement (n=53) 12
Slide 12: Baseline Characteristics by DRSS Response at Week 100 in Sham Patients
FAS, LOCF. Baseline Characteristics by DRSS Response at Week 100 in Sham Patients 21-step DRSS improvement (n=53) Age, mean (SD), years 54.6 (10.9) 57.7 (9.2) Female, n (%) 45 (56.3) 19 (35.8) HbA‘c, mean (SD), % 8.8 (1.6) 8.2 (1.5) Type 2 diabetes, n (%) 73 (91.3) 50 (94.3) Duration of diabetes, me
Slide 13: Univariate analysis at Week 100
Sex (male vs female) —_o———_- Hypertension (yes vs no) —o—_ Leakage area (per 5-mm?increase) Odds ratio (95% Cl) 0.00 0.50 1.00 1.50 2.00 Odds ratio (95% Cl) Favors 21-step DRSS improvement Favors no DRSS score improvement —— LOCF. Inferential results were derived from a logistic regression model ad
Slide 14: Multivariable Analysis: Baseline Factors Associated With No DRSS Score Improvement
Multivariable Analysis: Baseline Factors Associated With No DRSS Score Improvement and 21-Step DRSS Improvement at Week 100 . Nominal Odds ratio (95% Cl) P-value Sex (male vs female) —_o——_- 0.44 (0.20, 0.96) 0.0395 Hypertension (yes vs no) —_o———_ 0.26 (0.08, 0.84) 0.0247 Leakage area —-e— 1.26 (1.
Slide 15: Limitations
The results may not be generalizable to a broader clinic patient population, as clinical trial participants may have more strict control of medical comorbidities Medication use (insulin and lipid control medications) was assessed at baseline only ° This was a post hoc exploratory approach . The US F
Slide 16: Summary
Summary Proportion of Patients in the Sham Group Multivariable Analysis: Baseline Factors Associated With No DRSS Multivariable Analysis: Baseline Factors Associated With No DRSS by DRSS Response at Week 100 ‘Score Improvement and >1-Step DRSS Improvement at Week 52 ‘Score Improvement and 21-Step DR