For diabetic macular edema, brolucizumab shows ‘robust’ visual and structural gains

Two factors in the treatment of diabetic macular edema (DME) are well known; fluid persistence can reduce visual acuity results, and monthly intravitreal injections are difficult for patients with multiple comorbidities. The promise of brolucizumab is that, with its low molecular weight, it can be administered at a dose of 6 mg and can therefore work effectively in longer treatment intervals.

Previous studies have shown brolucizumab to be comparable to aflibercept in reducing retinal fluid in patients with neovascular age-related macular degeneration (nAMD). From now on, the data published in the American Journal of Ophthalmology presents the results of a phase III multicenter trial which demonstrates its efficacy at 52 weeks for the treatment of DME.

Two 100-week trials started in mid-2018; KESTRAL is conducted at 118 centers (ClinicalTrials.gov Identifier: NCT03481634) and KITE at 79 sites (ClinicalTrials.gov Identifier: NCT03481660), both conducted internationally.


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The 566 KESTRAL participants were randomized 1:1:1 to 3 arms: brolucizumab 3 mg, brolucizumab 6 mg, or aflibercept 2 mg, and 360 individuals from the KITE study were assigned 1:1 to brolucizumab 6 mg or aflibercept 2 mg. aflibercept 2 mg. After 5 loading doses 6 weeks apart for brolucizumab and 4 weeks for aflibercept, a masked investigator assessed participants at weeks 32, 36, and 48. Aflibercept injections followed a maintenance schedule target of 8 weeks and brolucizumab a target of 12 weeks, unless the disease activity assessment indicated a prior need of 8 weeks.

More than 50% of people treated with brolucizumab 6 mg in either trial were effectively maintained on a 12-week maintenance regimen for one year. The resulting median number of injections over 52 weeks was 7 in the brolucizumab arms and 9 for the aflibercept fixed interval groups.

At 52 weeks, KESTRAL patients receiving brolucizumab 6 mg had best corrected visual acuity (BCVA), a mean least-squares estimate of +9.2 letters versus +10.5 letters for aflibercept, and KITE participants on brolucizumab had gains of +10.6 letters over aflibercept reaching +9.4 letters, after adjusting for baseline BCVA and age. Data from the 2 studies were pooled to compare Diabetic Retinopathy Severity Scale (DRSS) scores. Using a 10% non-inferiority margin, brolucizumab 6 mg was non-inferior to aflibercept for the proportion of individuals achieving a DRSS score ≥ 2 best step at 52 weeks (P <.001>

Structural results for the 2 anti-VEGFs showed a treatment difference of 13.4% in favor of brolucizumab 6 mg for maintaining central subfield thickness (CST)

Serious ocular adverse events occurred in KESTRAL for 1.1% with brolucizumab 6 mg and 2.1% aflibercept, and in KITE, for 2.2% with brolucizumab and 1.7% aflibercept. AEs were specifically considered: intraocular inflammation (IOI), retinal vascular occlusion or endophthalmitis occurred in 0% to 1.7% in each group, except that mild to moderate IOI was observed in 3.7 % in the KESTRAL brolucizumab 6 mg cohort and 4.7% in the Ensemble 3 mg cohort. Most cases of IOI were mild to moderate and treated without sequelae.

The trials did not allow for an adjustment between the 8 and 12 week dosing regimens that would produce a ‘head to head’ comparison of the two biologics, which is a limitation of the design. Highlights included masked image graders in a central reading center, and the first time a 6-week initial loading phase was compared to the typical protocol of other 4-week EMR-prescribed anti-VEGFs .

Disclosures: The study was sponsored by Novartis AG. Several study authors disclosed affiliations with the biotechnology, pharmaceutical, and/or medical device industries. Please see the original citation for a full list of author disclosures.

The references

Brown DM, Emanuelli A, Bandello F, et al. KESTREL and KITE: results at 52 weeks of two pivotal phase III trials of brolucizumab for diabetic macular edema. Am J Ophthalmol. Published online January 13, 2022. doi:10.1016/j.ajo.2022.01.004

This article originally appeared on Ophthalmology Advisor

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