Novartis announced that the FDA has approved Beovu (brolucizumab-dbll) 6 mg for the treatment of diabetic macular edema (DME). Today’s approval represents the second FDA-approved indication for Beovu, which was first approved for the treatment of wet age-related macular degeneration in 2019.
The FDA approval was based on year 1 data from the phase 3, randomized, double-masked KESTREL and KITE studies, which met their primary endpoint of noninferiority in change in best-corrected visual acuity (BCVA) from baseline versus aflibercept at year one.1,2
In aggregate, a numerically lower proportion of patient eyes treated with Beovu had intraretinal fluid, subretinal fluid or both at week 52 versus eyes treated with aflibercept (in KESTREL 60.3% in the Beovu arm versus 73.3% in the aflibercept arm; in KITE 54.2% versus 72.9%, respectively; statistical significance was not tested).2
Through year 1, half of Beovu patients (55% in KESTREL and 50% in KITE) remained on a 12-week dosing interval following the loading phase.1,2 During this time (by week 52), patients received a median of seven Beovu injections.1,2 Patients treated with Beovu demonstrated a significant reduction from baseline in central subfield thickness (CST) starting at week 4 and continuing up to week 52.1,2
Per the approved BEOVU prescribing information, following the loading phase of five doses injected 6 weeks apart, patients should be treated once every 8 to 12 weeks.1 Throughout the KESTREL and KITE trials, aflibercept patients were dosed every 8 weeks, as recommended in its FDA-approved label.1,2
“The FDA approval of Beovu in DME marks a significant milestone for US DME patients, many of whom are of working age and struggle with treatment adherence while juggling multiple doctor’s visits every month,” Jill Hopkins, SVP and Global Development Unit Head, Ophthalmology, Novartis, said in a company news release.
“KESTREL and KITE were the first pivotal trials to assess an anti-VEGF on 6-week dosing intervals in the loading phase, suggesting Beovu may offer fewer injections from the start of treatment through year 1. We look forward to offering a new treatment option to help address the unmet needs of patients with DME. This FDA approval follows the recent European Commission approval and allows more patients around the world to potentially benefit from this important medicine,”Mrs. Hopkins added.
The most common adverse event (≥5%) reported in patients who received Beovu in the DME clinical trials was conjunctival hemorrhage.1 Intraocular inflammation (IOI) rates in KESTREL were 4.7% for brolucizumab 3 mg (including 1.6% retinal vasculitis), 3.7% for Beovu 6 mg (including 0.5% retinal vasculitis), and 0.5% for aflibercept 2 mg.2
IOI rates in KITE were equivalent (1.7%) between the Beovu 6 mg and aflibercept 2 mg arms with no retinal vasculitis reported.2 Retinal vascular occlusion was reported in KESTREL for brolucizumab 3 mg (1.1%) and 6 mg (0.5%), and in KITE for brolucizumab and aflibercept (0.6% each).2 In KESTREL, the percentage of patients who experienced ≥15 letter loss from baseline at year 1 was 1.6% for brolucizumab 3 mg, 0% for Beovu 6 mg and 0.5% for aflibercept.2 In KITE, the percentage of patients who experienced ≥15 letter loss from baseline at year 1 was 1.1% for Beovu 6 mg and 1.7% for aflibercept.2 Brolucizumab 6 mg is the commercialized dose of Beovu.1
Novartis remains committed to bringing Beovu to appropriate patients who may benefit from this important medicine. As of June 2022, Beovu is available as a pre-filled syringe in the US. This will provide eye care professionals an option that offers fewer steps than the vial.
About the KESTREL and KITE clinical trials
KESTREL and KITE are global, randomized, double-masked, phase 3, two-year studies comparing the safety and efficacy of Beovu and aflibercept in the treatment of patients with visual impairment due to DME.6,7
KESTREL and KITE involved 926 total patients in 36 countries.6,7 In the loading phase of both trials, patients in the Beovu arms were treated every 6 weeks for a total of five doses; patients in the aflibercept arms were treated every 4 weeks for a total of five doses, in line with its label.6,7
In the first year of the study, following the loading phase, patients in the Beovu arms were subsequently treated every 12 weeks, with those demonstrating disease activity moved to dosing every 8 weeks.6,7 After the loading phase, patients in the aflibercept arms were treated every 8 weeks.6,7