Brolucizumab shows favourable benefit–risk profile in diabetic macular oedema

At a dose of 6 mg, brolucizumab yields substantial visual gains and anatomical improvements in patients with diabetic macular oedema (DME) without increasing the risk of serious adverse ocular events when compared with aflibercept, according to data from two phase III trials.

A total of 566 DME patients were randomized to receive brolucizumab at either 3 mg or 6 mg, or aflibercept 2 mg in KESTREL, and 360 patients to either brolucizumab 6 mg or aflibercept 2 mg in KITE. Those on brolucizumab were given five loading doses every 6 weeks (q6w) followed by q12w dosing, with optional adjustment to q8w if disease activity was identified at predefined assessment visits. On the other hand, the aflibercept groups were administered five q4w dosing followed by a fixed q8w dosing.

Researchers assessed best-corrected visual acuity (BCVA) change from baseline to week 52 as the primary study endpoint. They also assessed the proportion of patients maintained on q12w dosing, change in Diabetic Retinopathy Severity Scale (DRSS) score, and anatomical and safety outcomes.

At week 52, brolucizumab 6 mg showed noninferiority (margin 4 letters) to aflibercept in terms of the primary endpoint. The mean BCVA increased by 9.2 vs 10.5 letters in KESTREL and by 10.6 vs 9.4 letters in KITE, respectively.

A higher number of patients achieved central subfield thickness (CSFT) <280 µm and fewer had persisting subretinal and/or intraretinal fluid on brolucizumab vs aflibercept, with more than half of those who received the 6-mg dose maintained on q12w dosing after loading.

In KITE, brolucizumab 6 mg also yielded more favourable improvements in CSFT over weeks 40–52 relative to aflibercept (p=0.001).

The incidence rates of serious adverse ocular events were 3.7 percent with brolucizumab 3 mg, 1.1 percent with brolucizumab 6 mg, and 2.1 percent with aflibercept in KESTREL; and 2.2 percent with brolucizumab 6 mg, and 1.7 percent with aflibercept in KITE.