DME DATA

Clinical Profile

KESTREL & KITE: Study design and baseline characteristics

Two pivotal Phase III trials vs aflibercept designed to compare efficacy and safety1

Image of the clinical trial data

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.

Chart of baseline characteristics used in the study
Chart of baseline characteristics used in the study

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

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Half (55% and 50%) of patients maintained
on Q12 at Week 52 1* 1*

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*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

Chart of secondary endpoint percentages

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

Image of a graph of the secondary endpoints data

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 intervals. 80% of Kestrel patients had no disease activity versus 76% of Kite patients.

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 intervals. 80% of Kestrel patients had no disease activity versus 76% of Kite patients.

*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

Of those patients who completed the first Q12 interval (ending at Week 36, ~9 out of 10 maintained Q12 through Week 52
Of those patients who completed the first Q12 interval (ending at Week 36, ~9 out of 10 maintained Q12 through Week 52
  • 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.

INDICATIONS AND USAGE

IMPORTANT SAFETY INFORMATION

COLLAPSE

EXPAND

IMPORTANT SAFETY INFORMATION

BEOVU® (brolucizumab-dbll) injection is indicated for the treatment of Neovascular (Wet) Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME).

CONTRAINDICATIONS

BEOVU is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to brolucizumab or any of the excipients in BEOVU. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, erythema, or severe intraocular inflammation.

WARNINGS AND PRECAUTIONS

Endophthalmitis and Retinal Detachment

Intravitreal injections, including those with BEOVU, have been associated with endophthalmitis and retinal detachment. Proper aseptic injection techniques must always be used when administering BEOVU. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately.

Retinal Vasculitis and/or Retinal Vascular Occlusion

Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of BEOVU. These immune-mediated adverse events may occur following the first intravitreal injection. Discontinue treatment with BEOVU in patients who develop these events. Patients treated with BEOVU who experience intraocular inflammation may be at risk of developing retinal vasculitis and/or retinal vascular occlusion and should be closely monitored. Patients should be instructed to report any change in vision without delay.

Increase in Intraocular Pressure

Acute increases in intraocular pressure (IOP) have been seen within 30 minutes of intravitreal injection, including with BEOVU. Sustained IOP increases have also been reported. Both IOP and perfusion of the optic nerve head must be monitored and managed appropriately.

Thromboembolic Events

Although there was a low rate of arterial thromboembolic events (ATEs) observed in the BEOVU clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. Arterial thromboembolic events are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The ATE rate in the two controlled 96-week neovascular AMD (nAMD) studies (HAWK and HARRIER) during the first 96-weeks was 4.5% (33 of 730) in the pooled brolucizumab arms compared with 4.7% (34 of 729) in the pooled aflibercept arms.

ADVERSE REACTIONS

Serious adverse reactions, including endophthalmitis, retinal detachment, retinal vasculitis and/or retinal vascular occlusion, increases in intraocular pressure, and arterial thromboembolic events, have occurred following intravitreal injections with BEOVU.

The most common adverse events (≥5% of patients) reported in nAMD clinical studies (HAWK and HARRIER) in patients who received BEOVU were vision blurred, cataract, conjunctival hemorrhage, vitreous floaters, and eye pain. The most common adverse event (≥5% of patients) reported in DME clinical studies (KITE and KESTREL) in patients who received BEOVU was conjunctival hemorrhage.

In a clinical study (MERLIN), patients with nAMD who received BEOVU every 4-week maintenance dosing experienced a higher incidence of intraocular inflammation (including retinal vasculitis) and retinal vascular occlusion than patients who received BEOVU every 8- or 12-week maintenance dosing in the clinical studies (HAWK and HARRIER). The interval between 2 BEOVU doses during maintenance treatment should not be less than 8 weeks.

As with all therapeutic proteins, there is a potential for an immune response in patients treated with BEOVU. Anti-brolucizumab antibodies were detected in the pre-treatment sample of 36% to 64% of treatment-naive patients. After initiation of dosing, anti-brolucizumab antibodies were detected in at least one serum sample in 53% to 76% of patients treated with BEOVU. Intraocular inflammation was observed in 6% of patients with anti-brolucizumab antibodies detected during dosing with BEOVU in clinical trials. Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, are immune-mediated adverse events related to exposure to BEOVU. This treatment-emergent antibody response may develop following the first intravitreal injection. Anti-brolucizumab antibodies were not associated with an impact on clinical efficacy.

INDICATIONS AND USAGE

BEOVU® (brolucizumab-dbll) injection is indicated for the treatment of Neovascular (Wet) Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME).

Please see full Prescribing Information for BEOVU.