ABOUT BEOVU

Study Design

Study design and baseline characteristics

Head-to-head trials designed to determine patients eligible for Q121,2

BEOVU Clinical Study Design BEOVU Clinical Study Design
WEEK 16
DAA CRITERIA

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

BEOVU was studied in 730 patients worldwide1,2

  • Baseline ocular characteristics were well balanced across treatment arms3,4

  • All patients were treatment na´ve2

BEOVU Baseline Patient Characteristics BEOVU Baseline Patient Characteristics

AMD=age-related macular degeneration; BCVA=best corrected visual acuity; CNV=choroidal neovascularization; CST=central subfield thickness; DAA=disease activity assessment (comprised of functional [BCVA] and anatomical parameters [IRF and/or SRF, CST, sub-RPE]); sub-RPE=sub-retinal pigment epithelium; ETDRS=Early Treatment Diabetic Retinopathy Study; IRF=intraretinal fluid; SRF=sub-retinal fluid; Q8=treatment every 8 weeks; Q12=treatment every 12 weeks.

*Maintenance phase continued through study end (Week 96).3,4

DAAs occurred at Weeks 16, 20, 32, and 44 with additional assessments in HARRIER at Weeks 28 and 40.3,4

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; 2018. 4. Data on file. RTH258-C002 Clinical Study Report. Novartis Pharmaceuticals Corp; 2018.

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.