Brolucizumab Noninferior to Aflibercept for Diabetic Macular Edema

Brolucizumab (Beovu) proved noninferior to aflibercept (Eylea) for visual outcomes among patients with diabetic macular edema (DME), the phase III KINGFISHER trial showed.

In over 500 patients with DME, the best-corrected visual acuity — measured by Early Treatment Diabetic Retinopathy Study letter score — changes from baseline at week 52 were similar with the two drugs: a 12.2-letter improvement with brolucizumab versus an 11.0-letter improvement with aflibercept (noninferiority margin 4, P<0.001), reported Andrés Emanuelli, MD, of the University of Puerto Rico School of Medicine in Arecibo, and colleagues.

In addition, brolucizumab outperformed the older anti-vascular endothelial growth factor (VEGF) drug in the proportion of eyes without subretinal and intraretinal fluid (41.6% vs 22.2%, respectively, P<0.001) and mean central subfield thickness change from baseline at week 52 (-237.8 μm vs -196.5 μm, P<0.001), they noted in JAMA Ophthalmology.

“Fewer injections to dryness may improve patient compliance and reduce healthcare expenditure, if this truly translates to reduced treatment burden in clinical practice,” the authors wrote. “Approximately 30% to 40% of patients have persistent DME despite frequent treatment with aflibercept or ranibizumab [Lucentis]. Thus, there remains an unmet need in that improved drying with brolucizumab may be a clinical advantage.”

The authors noted that the dosing regimen evaluated is not approved for brolucizumab based on a higher reported frequency of intraocular inflammation, retinal vasculitis, and retinal vascular occlusion as observed in the MERLIN study in neovascular age-related macular degeneration.

Raj Maturi, MD, an ophthalmologist at the Indiana University School of Medicine in Indianapolis, told MedPage Today that DME is one of the most common causes of vision loss in patients with diabetes. Anti-VEGF injections reduce fluid buildup and help to preserve vision, he said.

He noted that the more rapid drying with brolucizumab is “a huge deal,” especially in light of the fact that fluid may return and cause DME in the future since diabetes is a lifetime condition. Follow-up visits can help track the condition, but many patients skip them for various reasons, he added.

However, he also noted that brolucizumab has higher rates of adverse effects than other anti-VEGF therapies, and he prefers to use it as a second-line therapy after other drugs such as aflibercept and bevacizumab (Avastin).

For this trial, Emanuelli and team included 517 patients with DME from September 2019 to March 2020. Mean age was 60.7, 57.8% were men, 84-85% were white, and 95% had type 2 diabetes. Most patients had not previously received anti-VEGF therapy (70-73%).

The participants were randomized 2:1 to intravitreal injections of brolucizumab 6 mg or aflibercept 2 mg every 4 weeks. The primary endpoint was change from baseline in best-corrected visual acuity at week 52.

Looking at adverse effects, intraocular inflammation occurred in 4% of patients with brolucizumab versus 2.9% with aflibercept, retinal vasculitis occurred in 0.9% and 0.6%, and retinal vascular occlusion occurred in 0.3% and 0.6%. One patient in the brolucizumab arm had a retinal artery occlusion, and one patient in the aflibercept arm had a mild retinal artery embolism.

The study did not examine cost or cost-effectiveness. Brolucizumab costs about $2,036 per dose, while aflibercept is about $1,958 per dose. According to Maturi, a much cheaper option is bevacizumab, which he said is extremely inexpensive, at $50 or $100 a dose.

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