Brolucizumab vs PRP in CONDOR for Proliferative Diabetic Retinopathy

Key Takeaways

• Visual acuity outcomes favored brolucizumab over PRP at week 54 in this randomized PDR comparison.
• Measures of disease control also favored brolucizumab, with more eyes free of active PDR and fewer CI-DME events and vision-threatening complications.
• Overall ocular adverse events were less common with brolucizumab, while intraocular inflammation including retinal vasculitis was reported more often than with PRP.

At week 54 in proliferative diabetic retinopathy, brolucizumab met the prespecified noninferiority goal for best-corrected visual acuity and also outperformed PRP. In the CONDOR trial, least-squares mean BCVA changed by 0.2 letters with brolucizumab and by -4.2 letters with PRP, a 4.4-letter difference (95% CI, 2.4-6.4; P<.001). The analysis reflects the planned 54-week readout of this ongoing randomized comparison in proliferative diabetic retinopathy.

CONDOR was a 96-week, 2-arm, single-masked, multicenter, phase 3 randomized clinical trial conducted at 152 sites across 16 countries. Eligible participants had diabetes and proliferative diabetic retinopathy in the study eye, no previous PRP in that eye, and no center-involved DME at screening; 689 were randomized 1:1. Brolucizumab 6 mg was given every 6 weeks for 3 loading doses, then every 12 weeks, with 6-week extensions from week 48 up to 24 weeks. PRP was delivered in 1 to 4 sessions up to week 12, with additional PRP as needed. The primary endpoint was BCVA change at week 54, and secondary outcomes included no PDR, center-involved DME, DRSS change, vision-threatening complications, and safety.

At week 54, 63.6% of brolucizumab-treated eyes and 22.4% of PRP-treated eyes had no PDR, a 39.4-point between-group difference (95% CI, 32.0-46.8; P<.001). Center-involved DME events occurred in 31.1% and 72.7%, respectively, for a -41.1-point difference (95% CI, -48.0 to -34.2; P<.001). Vision-threatening complications were reported in 33.7% of the brolucizumab arm and 75.4% of the PRP arm. At least 2-step DRSS improvement occurred in 45.4% versus 20.4%, and at least 3-step improvement occurred in 20.6% versus 10.8%. Across secondary measures at week 54, disease control favored brolucizumab over PRP.

Ocular adverse events occurred in 34.3% of the brolucizumab arm and 49.1% of the PRP arm. Intraocular inflammation, including retinal vasculitis, was reported in 5.2% versus 0.6%, with a higher frequency in the brolucizumab arm. Serious ocular adverse events were reported in 2.9% and 6.4%, while retinal vascular occlusion was reported in 0.9% and 0.3%, respectively. Investigators reported no new safety findings for brolucizumab in this proliferative diabetic retinopathy population. Overall, fewer ocular adverse events but more inflammatory events were reported with brolucizumab.

The current analysis covers week 54 of an ongoing 96-week trial, and later results are not yet available. Although center-involved DME was excluded at screening by investigator assessment, 284 enrolled eyes (41.3%) were later found by central reading center review to have CST greater than 280 µm using the study's CRC threshold. The study did not collect DME treatment-decision data, limiting interpretation of the DME-related findings. Investigators also noted that a meaningful minority of participants were not central reading center–confirmed to have PDR, reflecting variability in baseline severity assessment. The findings apply to the week-54 CONDOR analysis rather than the trial's final 96-week results.