SEE THE
STUDY DESIGN

The safety and efficacy of BEOVU were assessed in 2 randomized, multicenter, double-masked, active-controlled, 2-year, Phase III studies in patients with wet AMD (N=1459). The primary endpoint demonstrated noninferiority in mean change in BCVA from baseline to Week 48 vs aflibercept as measured by ETDRS letters. Patients were randomized to either BEOVU 6 mg or aflibercept 2 mg (Q8 per label). Disease Activity Assessments (DAAs) were conducted throughout the trial at prespecified intervals. After 3 initial monthly doses, treating physicians decided whether to treat each patient on a Q8 or Q12 interval guided by visual and anatomical measures of disease activity, although the utility of these measures has not been established. Patients with disease activity at Week 16 or at any DAA could be adjusted to Q8 for the remainder of the study.1,2

STUDY DESIGN

BEOVU DATA

Clinical Profile

Achieved similar mean change in BCVA at Week 481

Visual gains achieved with BEOVU were similar to aflibercept1,2

Primary endpoint: Mean change in BCVA vs aflibercept from baseline to Week 481,3,4

Hawk Created with Sketch.
Harrier Created with Sketch.

The primary endpoint was to demonstrate efficacy in mean change in BCVA from baseline at Week 48, measured by ETDRS letters. Both studies confirmed the hypothesis of noninferiority at Week 48 with a margin of 4.0 letters.1,2

Over half of patients maintained on Q12 at Week 481

The only anti-VEGF in wet AMD recommended to start patients on Q8-Q12 intervals immediately after loading1,5,6

Secondary endpoint: % of patients on Q12 with BEOVU at Week 481,2

HAWK

10%
of patients were
on Q12

HARRIER

10%
of patients were
on Q12

All remaining patients were on Q8.2*

Dosage & Administration

The recommended dose for BEOVU is 6 mg (0.05 mL of 120 mg/mL solution) monthly (approximately every 25-31 days) for the first 3 doses, followed by 1 dose of 6 mg every 8-12 weeks. BEOVU is administered by intravitreal injection.1

BCVA=best corrected visual acuity; ETDRS=Early Treatment Diabetic Retinopathy Study; Q8=treatment every 8 weeks; Q12=treatment every 12 weeks; VEGF=vascular endothelial growth factor.

*In HAWK, 0 patients treated with BEOVU discontinued the study due to lack of efficacy prior to Week 48. In HARRIER, 1 patient treated with BEOVU discontinued the study due to lack of efficacy prior to Week 48.2

Greater CST reductions2

Greater CST reductions were seen as early as Week 16, and at Week 482

Secondary endpoint: CST reductions vs aflibercept from baseline to Week 483,4,7

Hawk Created with Sketch.
Harrier Created with Sketch.

In HAWK, superior CST reductions were achieved at Week 16 and Week 48. In HARRIER, P values are nominal and not adjusted for multiplicity.2 Clinical significance has not been established. No conclusions of efficacy may be drawn.

Results seen with
over half of patients on Q12 at Week 48
(56% and 51%)1

CST=central subfield thickness.

An actual patient's CST response8

Actual patient OCT scans taken by HAWK investigators are representative of the
average CST response from baseline to Week 48. Individual results may vary.

BEOVU Patient OCT Scans BEOVU Patient OCT Scans

BASELINE

CST:498μm

IRF/SRF Patients at Weeks 16 IRF/SRF Patients at Weeks 16

WEEK 16

CST:
300μm

IRF/SRF Patients at Weeks 48 IRF/SRF Patients at Weeks 48

WEEK 48

CST:
313μm

OCT=optical coherence tomography.

Fewer patients with IRF and/or SRF2

Fewer patients with IRF and/or SRF as early as Week 16, and at Week 482

Secondary endpoint: % of patients with IRF and/or SRF vs aflibercept at Weeks 16 and 483,4

Hawk Created with Sketch.
Harrier Created with Sketch.

In HAWK, superior reductions in the percentage of patients with IRF and/or SRF were achieved at Week 16 and Week 48. In HARRIER P values are nominal and not adjusted for multiplicity.2 Clinical significance has not been established. No conclusions of efficacy may be drawn.

At Week 48,
over half of patients in the study
were maintained on Q12

(56% and 51%)1

IRF=intraretinal fluid; SRF=sub-retinal fluid.

References: 1. Beovu [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; October 2019. 2. Dugel PU, Koh A, Ogura Y, et al, on behalf of the HAWK and HARRIER Study Investigators. HAWK and HARRIER: Phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2019. doi: 10.1016/j.ophtha.2019.04.017. 3. Data on file. RTH258-C001 Clinical Study Report. Novartis Pharmaceuticals Corp; December 2018. 4. Data on file. RTH258-C002 Clinical Study Report. Novartis Pharmaceuticals Corp; December 2018. 5. Eylea [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc; 2019. 6. Lucentis [prescribing information]. South San Francisco, CA: Genentech, Inc; 2018. 7. Data on file. RTH258-C001 & RTH258-C002 CST. Novartis Pharmaceuticals Corp; September 2019. 8. Data on file. RTH258-C001 OCT image. Novartis Pharmaceuticals Corp; September 2019.

INDICATIONS AND USAGE

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

IMPORTANT SAFETY INFORMATION

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 Detachments

Intravitreal injections, including those with BEOVU, have been associated with endophthalmitis and retinal detachments. 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.

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 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, increases in intraocular pressure, and arterial thromboembolic events have occurred following intravitreal injections with BEOVU.

The most common adverse events (≥5% of patients) with BEOVU were vision blurred, cataract, conjunctival hemorrhage, vitreous floaters and eye pain.

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 52% of treatment naive patients. After initiation of dosing, anti-brolucizumab antibodies were detected in at least one serum sample in 53% to 67% of patients treated with BEOVU. Intraocular inflammation was observed in 6% of patients with anti-brolucizumab antibodies detected during dosing with BEOVU. The significance of anti-brolucizumab antibodies on the clinical effectiveness and safety of BEOVU is not known.

Please see the Important Safety Information and full Prescribing Information for BEOVU.