WET AMD DATA

Study Design

Study design and baseline characteristics

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

Chart of the Hawk and Harrier clinical trial data

HAWK & HARRIER: 2-head-to-head clinical trials for BEOVU vs aflibercept1,2

Chart of the Hawk and Harrier clinical trial data HAWK & HARRIER:
2-head-to-head clinical trials for
BEOVU vs aflibercept1,2

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

*DAAs occurred at Weeks 16, 20, 32, 44, 56, 68, 80, and 92 with additional assessments in HARRIER at Weeks 28, 40, 52, 64, 76, and 88.3,4

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). 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 naive2

Chart of the patient characteristics of the Hawk and Harrier clinical trial Chart of the patient characteristics of the Hawk and Harrier clinical trial

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]); ETDRS=Early Treatment Diabetic Retinopathy Study; IRF=intraretinal fluid; Q8=treatment every 8 weeks; Q12=treatment every 12 weeks; SRF=subretinal fluid; sub-RPE=subretinal pigment epithelium.

References: 1. Beovu [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; May 2022. 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. 2020;127(1):72-84.
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.

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.