Brolucizumab in the Treatment of Proliferative Diabetic Retinopathy: The CONDOR Randomized Clinical Trial.

Importance: CONDOR (Study of Efficacy and Safety of Brolucizumab Versus Panretinal Photocoagulation Laser in Patients With Proliferative Diabetic Retinopathy) is a large-scale, company-sponsored randomized clinical trial to assess the unique 6-week (loading) and 12-week (maintenance) brolucizumab dosing regimen in proliferative diabetic retinopathy (PDR). Objective: To assess the efficacy and safety of brolucizumab, 6 mg, compared with panretinal laser photocoagulation (PRP) in eyes with PDR. Design, Setting, and Participants: CONDOR is a 96-week, 2-arm, single-masked, multicenter, phase 3 randomized clinical trial conducted across 16 countries at 152 sites. Data were analyzed from December 4, 2020 (first participant first visit), to October 30, 2023 (cutoff date). Patients with diabetes and PDR diagnosis and no previous PRP treatment in the study eye were eligible for inclusion. Intervention: Patients randomized to receive brolucizumab, 6 mg, received 3 loading doses every 6 weeks, followed by every 12 weeks, with the option from week 48 onward to extend the treatment interval by 6 weeks at a time up to 24 weeks based on disease activity. Patients randomized to PRP received treatment in 1 to 4 sessions up to week 12, followed by additional PRP treatment as needed. Main Outcomes and Measures: The primary outcome measure was change from baseline in best-corrected visual acuity (BCVA) at week 54. Secondary outcomes included change in DR progression, prevention of center-involved diabetic macular edema, change in Diabetic Retinopathy Severity Score levels, and safety. Results: A total of 689 participants were randomized in a 1:1 ratio to brolucizumab, 6 mg (n = 347), or PRP (n = 342), and 572 randomized participants completed the week 54 visit. Mean (SD) patient age was 53.9 (11.39) years, 276 patients (40.1%) were female, and mean (SD) BCVA (letter score) at baseline was 77.1 (10.55) (Snellen equivalent, 20/32). Brolucizumab, 6 mg, was noninferior and superior to PRP for BCVA change at week 54 (least-squares mean [SE] change in letter score: 0.2 [0.72] vs -4.2 [0.73]; difference, 4.4; 95% CI, 2.4-6.4; P < .001). A higher proportion of patients receiving brolucizumab, 6 mg, had no PDR at week 54 vs patients receiving PRP (187 [63.6%] vs 65 [22.4%]; difference, 39.4; 95% CI, 32.0-46.8; P < .001). Ocular adverse events were reported in 119 patients (34.3%) and 168 patients (49.1%) in the brolucizumab, 6 mg, arm and PRP arm, respectively. The rate of intraocular inflammation, including retinal vasculitis, was 18 of 347 patients (5.2%) in the brolucizumab, 6 mg, arm and 2 of 342 patients (0.6%) in the PRP arm. Conclusions and Relevance: In the CONDOR randomized clinical trial, brolucizumab was superior to PRP in preserving visual acuity and may be a viable treatment alternative to PRP monotherapy for patients with PDR. Trial Registration: ClinicalTrials.gov Identifier: NCT04278417.