Clinical Studies:
KINGFISHER
Citation: Singh RP, Barakat MR, Ip MS, et al. Efficacy and safety of brolucizumab for diabetic macular edema: the kingfisher randomized clinical trial. JAMA Ophthalmol. 2023;141(12):1152-1160.
Key Points
- KINGFISHER is the only study testing monthly (Q4W) brolucizumab in DME.
- Brolucizumab achieved comparable vision gains and better fluid resolution than aflibercept.
- Fixed monthly regimen may benefit patients with high disease activity.
- Ocular safety signals remain consistent with earlier trials.
Study Design
Phase III, randomized, double-masked, multicenter clinical trial. 52 weeks. Comparator: Brolucizumab vs. aflibercept. Focus: Intensive (monthly) dosing regimen in patients with diabetic macular edema (DME).
Study Objectives and Endpoints
Primary Objective: Demonstrate non-inferiority of brolucizumab 6 mg to aflibercept 2 mg in visual acuity improvement at Week 52.
Primary Endpoint: Mean change in best-corrected visual acuity (BCVA) from baseline to Week 52.
Key Secondary Endpoints: Change in central subfield thickness (CST), absence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), safety outcomes.
Randomization Scheme and Interventions
Randomization: 1:1.
Brolucizumab 6 mg: Monthly (Q4W) intravitreal injections.
Aflibercept 2 mg: Monthly (Q4W) intravitreal injections.
Study Subjects
- Population: Patients with center-involving DME and decreased vision.
- Inclusion: Treatment-naïve or previously treated, but not adequately controlled.
Study Eye Inclusion Criteria
- BCVA between 78 and 24 ETDRS letters (approx. 20/32 to 20/320).
- Central-involved DME with CST ≥ 300 μm.
- Clear ocular media and good visualization of the posterior segment.
Treatment
- Both drugs administered monthly for 52 weeks.
- No interval extension — fixed Q4W regimen.
Assessment Methods
- BCVA: ETDRS letter score.
- Optical Coherence Tomography (OCT): For CST, IRF, and SRF evaluation.
- Safety Monitoring: Adverse events, with focus on intraocular inflammation (IOI), retinal vasculitis, and vascular occlusion.
Results
- Efficacy:
- Brolucizumab was non-inferior to aflibercept in BCVA gains at Week 52. Brolucizumab showed a 12.2-letter gain, while aflibercept showed an 11.0-letter gain.
- Greater reductions in CST with brolucizumab: mean CST reduction was 237.8 µm with brolucizumab vs 196.5 µm for aflibercept.
- Higher proportion of eyes free of IRF/SRF in the brolucizumab arm at week 52 (41.8%) compared to aflibercept (21.8%).
- Safety:
- IOI events were more frequent with brolucizumab, consistent with prior studies. Incidence of IOI: 4.0% (brolucizumab) vs 2.9% (aflibercept).
- Retinal vasculitis: 0.9% (brolucizumab) vs 0.6% (aflibercept).
Conclusions
- Monthly brolucizumab provides significant visual and superior anatomical outcomes compared to monthly aflibercept.
- Brolucizumab use requires careful monitoring for signs of IOI.