Preliminary data from KITE, KESTREL trials show positive outcomes of brolucizumab in DME
Click Here to Manage Email Alerts
First data from the KITE and KESTREL trials showed encouraging efficacy and safety outcomes of brolucizumab in the treatment of diabetic macular edema.
“Both studies demonstrated that brolucizumab 6 mg was noninferior to aflibercept in mean change of [best corrected visual acuity] at week 52 with fewer injections. Central subfield thickness improved significantly, and there was a higher proportion of patients with fluid resolution,” David M. Brown, MD, said at the virtual Association for Research in Vision and Ophthalmology meeting.
The safety profile was, overall, “well balanced,” he said.
KITE and KESTREL are 2-year, ongoing, multicenter trials. In KESTREL, patients were randomly assigned to Beovu (brolucizumab, Novartis) 3 mg, brolucizumab 6 mg or Eylea (aflibercept, Regeneron) 2 mg, while in KITE, randomization was between brolucizumab 6 mg and aflibercept 2 mg. Both the brolucizumab and aflibercept groups received five loading doses, respectively at 6 weeks and monthly intervals. Following this, aflibercept was administered every 8 weeks and brolucizumab either every 8 weeks or every 12 weeks. Baseline visual acuity in all groups was between 63 letters and 66 letters, central subfield thickness was 450 µm to 480 µm, and almost all patients had universal edema with intraretinal and subretinal fluid present.
The 6 mg arms showed noninferiority to aflibercept, with a comparable gain of 9 to 10 letters at week 52 achieved with a lower number of injections at longer intervals.
“In the brolucizumab arms, we treated patients either Q12W or Q8W based on disease activity. In both KESTREL and KITE, more than 50% of patients were maintained on a Q12W interval thorough week 52 with brolucizumab 6 mg. The specific number of active injections was nine in the aflibercept arm compared to seven in each arm of brolucizumab,” Brown said.
Of note, the 3 mg brolucizumab arm was not noninferior to aflibercept.
Overall, brolucizumab showed superior drying efficacy for both intraretinal and subretinal fluid. Anatomically, more patients (54% to 57% vs. 40% to 41%) achieved the prespecified endpoint of central subfield thickness of less than 280 µm at 52 weeks. More eyes with disease activity, shown by presence of both intraretinal and subretinal fluid, were found in the aflibercept arms, specifically, 72% to 73% with aflibercept as compared with 54% to 60% with brolucizumab in the two studies.
Overall, brolucizumab had a well-tolerated safety profile, “with the exception of a few cases of intraocular inflammation,” Brown said.
“In KITE, we found no difference in serious adverse events between the two groups, with one case each of retinal artery occlusion, neither associated with inflammation or vasculitis,” he said.
In KESTREL, 16 eyes treated with brolucizumab developed intraocular inflammation, the majority in the 3 mg arm, vs. one case in the aflibercept arm. There were also four cases of retinal vasculitis and three cases of retinal vascular occlusion with brolucizumab vs. none with aflibercept.
“One patient had both retinal vasculitis and retinal vascular occlusion. Both these events resolved without treatment, and at the week 52 endpoint, VA had increased by 14 letters from baseline,” Brown said. “Safety data show that diabetes, the underlying vascular disease, didn’t seem to have any negative effect on the brolucizumab-related incidence of intraocular inflammation.”
Collapse
Brown DM, et al. Brolucizumab for the treatment of visual impairment due to diabetic macular edema: 52-week results from the KITE and KESTREL studies. Presented at: Association for Research in Vision and Ophthalmology annual meeting; May 1-7, 2021 (virtual meeting).
Read more about
Click Here to Manage Email Alerts