DME DATA
Clinical Profile
KESTREL & KITE: Study design and baseline characteristics
Two pivotal Phase III trials vs aflibercept designed to compare efficacy and safety1
Disease activity was based on functional and anatomical parameters and evaluated by a masked investigator to determine if BEOVU patients could remain on Q12.1
DAA=disease activity assessment; Q4=treatment every 4 weeks; Q6=treatment every 6 weeks; Q8=treatment every 8 weeks; Q12=treatment every 12 weeks.
*Disease activity was assessed at various time points by a masked investigator.1
†DAAs were conducted by a physician during the first 12-week interval (at Weeks 32 and 36) and at each subsequent scheduled
12-week treatment visit.1
‡More frequent treatment was determined by functional and anatomical parameters.1
Study design
The safety and efficacy of BEOVU were assessed in 2 randomized, multicenter, double-masked, active-controlled, 1-year studies in patients with DME (N=926). Patients were randomized to either BEOVU 6 mg or aflibercept 2 mg in both KESTREL and KITE. The primary endpoint demonstrated noninferiority in mean change in BCVA from baseline to Week 52 vs aflibercept as measured by ETDRS letters (P<0.001). After 5 initial doses every 6 weeks, BEOVU patients were treated on a Q12 interval with the option of adjusting to a Q8 dosing interval based on disease activity. Disease activity was assessed by changes in VA and/or anatomical parameters, including CST and/or presence of IRF/SRF, although the utility of the specific action parameters used has not been established. DAAs were conducted throughout the trial at prespecified intervals. Patients with disease activity at any DAA could be adjusted to a Q8 treatment interval for the remainder of the study.1,2
BCVA=best corrected visual acuity; CST=central subfield thickness; DME=diabetic macular edema; ETDRS=Early Treatment Diabetic Retinopathy Study; IRF=intraretinal fluid; SRF=subretinal fluid; VA=visual acuity.
Select baseline characteristics in KESTREL & KITE
All patients enrolled in KESTREL and KITE were treatment naive.
SD=standard deviation.
Patients on BEOVU experienced comparable mean change in BCVA vs aflibercept at Week 521
Primary endpoint: Mean change in BCVA from baseline with BEOVU vs aflibercept1,2*
Primary endpoint: Mean change in BCVA from baseline with BEOVU vs aflibercept1,2*
*The primary endpoint was to demonstrate noninferiority of BEOVU vs aflibercept in mean change from baseline in BCVA at Week 52 as measured by ETDRS letters. Both studies confirmed the hypothesis of noninferiority at Week 52 with a margin of 4 letters.1,2
†One-sided P value referring to the noninferiority hypothesis with a noninferiority margin of 4 letters.2
Half (55% and 50%) of patients maintained
on Q12 at Week 52 1*† 1*†
*Excluding censored subjects, who were considered to no longer be under risk for a Q8-need identification at later visits.3,4 Censoring in a study is when there is incomplete information about a participant or observation.
†All remaining patients were maintained on Q8.1
An actual patient's CST response on a Q8 interval5
Actual patient OCT scans taken by KITE investigators are representative
of the average CST response. Individual results may vary.
An actual patient's CST response on a Q12 interval6
Actual patient OCT scans taken by KITE investigators are representative
of the average CST response. Individual results may vary.
OCT=optical coherence tomography.
A lower percentage of BEOVU patients had IRF and/or SRF
at Week 522
Secondary endpoint: Patients with IRF and/or SRF on BEOVU vs aflibercept2
Secondary endpoint: Patients with IRF and/or SRF on BEOVU vs aflibercept2
Statistical significance not tested. Clinical significance has not been established. No conclusions of efficacy may be drawn.
More patients on BEOVU showed reductions in CST at Week 522
Secondary endpoint: Patients with CST <280 μm2
Secondary endpoint:
Patients with CST <280 μm2
Statistical significance not tested. Clinical significance has not been established. No conclusions of efficacy may be drawn.
After 5 initial doses, over 75% of BEOVU patients had no signs of disease activity2*†
At Week 32, patients were given a disease activity assessment
to determine their treatment intervals2
At Week 32, patients were given a disease activity assessment to determine their treatment intervals2
*Disease activity was prespecified.1
†Disease activity was assessed by changes in VA and/or anatomical parameters, including CST and/or presence of IRF/SRF, although the utility of the specific action parameters used has not been established.1
BEOVU patients on Q12 had a high probability of remaining
on Q121
-
In KESTREL and KITE, half of BEOVU patients (55%, 50%) remained on Q12 at Week 521
-
Potential for fewer injections at Year 1: Patients on BEOVU received 7 median injections. Patients on aflibercept received 9 median injections2
The recommended dose for BEOVU is 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every 6 weeks (approximately every 39-45 days) for the first 5 doses, followed by 6 mg (0.05 mL) by intravitreal injection every 8-12 weeks.1
*Patients identified as eligible for Q12 dosing after the first 12-week interval (ie, no disease activity during the first Q12 interval).1
†n=155/170 (91%); patients with no Q8 need at Week 36, excluding censored patients. Censored patients were considered to no
longer be under risk for Q8-need identification at later visits.3,4 Censoring in a study is when there is incomplete information about a participant or observation.
References: 1. Beovu [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; May 2022. 2. Brown DM, Emanuelli A, Bandello F, et al. KESTREL & KITE: 52-week results from two phase III pivotal trials of brolucizumab for diabetic macular edema. Am J Ophthalmol. 2022;238:157-172. doi:10.1016/j.ajo.2022.01.004. Online ahead of print. 3. Data on file. CRTH258B2301 FIR v1.0. Novartis Pharmaceuticals Corp; 2020. 4. Data on file. CRTH258B2302 FIR v2.0. Novartis Pharmaceuticals Corp; 2020. 5. Data on file. Q8 Patient. Novartis Pharmaceuticals Corp; 2022. 6. Data on file. Q12 Patient. Novartis Pharmaceuticals Corp; 2022.
