Source: FDA, National Drug Code (US) Revision Year: 2020
BEOVU is contraindicated in patients with ocular or periocular infections.
BEOVU is contraindicated in patients with active intraocular inflammation.
BEOVU is contraindicated in patients with known hypersensitivity to brolucizumab or any of the excipients in BEOVU. Hypersensitivity reactions may manifest as rash, pruritus, urticaria, erythema, or severe intraocular inflammation.
Intravitreal injections, including those with BEOVU, have been associated with endophthalmitis and retinal detachment [see Contraindications (4.1) and Adverse Reactions (6.1)]. 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 [see Dosage and Administration (2.4) and Patient Counseling Information (17)].
Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of BEOVU [see Contraindications (4.2) and Adverse Reactions (6.1)]. Patients should be instructed to report any change in vision without delay.
Acute increases in intraocular pressure (IOP) have been seen within 30 minutes of intravitreal injection, including with BEOVU [see Adverse Reactions (6.1)]. Sustained IOP increases have also been reported. Both IOP and perfusion of the optic nerve head must be monitored and managed appropriately [see Dosage and Administration (2.4)].
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 [see Clinical Studies (14.1)].
The following potentially serious adverse reactions are described elsewhere in the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in one clinical trial of a drug cannot be directly compared with rates in the clinical trials of the same or another drug and may not reflect the rates observed in practice.
A total of 1088 patients, treated with brolucizumab, constituted the safety population in the two controlled neovascular AMD Phase 3 studies (HAWK and HARRIER) with a cumulative 96 week exposure to BEOVU, and 730 patients treated with the recommended dose of 6 mg [see Clinical Studies (14.1)].
Adverse reactions reported to occur in ≥1% of patients who received treatment with BEOVU pooled across HAWK and HARRIER, are listed below in Table 1.
Table 1. Common Adverse Reactions (≥1%) in the HAWK and HARRIER wet AMD Clinical Trials:
| Adverse Drug Reactions | BEOVU (N=730) | Active Control (aflibercept) (N=729) |
|---|---|---|
| Vision blurreda | 10% | 11% |
| Cataract | 7% | 11% |
| Conjunctival hemorrhage | 6% | 7% |
| Vitreous floaters | 5% | 3% |
| Eye pain | 5% | 6% |
| Intraocular inflammationb | 4% | 1% |
| Intraocular pressure increased | 4% | 5% |
| Retinal hemorrhage | 4% | 3% |
| Vitreous detachment | 4% | 3% |
| Conjunctivitis | 3% | 2% |
| Retinal pigment epithelial tear | 3% | 1% |
| Corneal abrasion | 2% | 2% |
| Hypersensitivityc | 2% | 1% |
| Punctate keratitis | 1% | 2% |
| Retinal tear | 1% | 1% |
| Endophthalmitis | 1% | < 1% |
| Blindnessd | 1% | < 1% |
| Retinal artery occlusion | 1% | < 1% |
| Retinal detachment | 1% | < 1% |
| Conjunctival hyperemia | 1% | 1% |
| Lacrimation increased | 1% | 1% |
| Abnormal sensation in eye | 1% | 2% |
| Detachment of retinal pigment epithelium | 1% | < 1% |
a Including vision blurred, visual acuity reduced, visual acuity reduced transiently, and visual impairment.
b Including anterior chamber cell, anterior chamber flare, anterior chamber inflammation, chorioretinitis, eye inflammation, iridocyclitis, iritis, retinal vasculitis, retinal vascular occlusion, uveitis, vitreous haze, vitritis.
c Including urticaria, rash, pruritus, erythema.
d Including blindness, blindness transient, amaurosis, and amaurosis fugax.
As with all therapeutic proteins, there is a potential for an immune response in patients treated with BEOVU. The immunogenicity of BEOVU was evaluated in serum samples. The immunogenicity data reflect the percentage of patients whose test results were considered positive for antibodies to BEOVU in immunoassays. The detection of an immune response is highly dependent on the sensitivity and specificity of the assays used, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to BEOVU with the incidence of antibodies to other products may be misleading.
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.
There are no adequate and well-controlled studies of BEOVU administration in pregnant women.
Based on the anti-VEGF mechanism of action for brolucizumab [see Clinical Pharmacology (12.1)], treatment with BEOVU may pose a risk to human embryo-fetal development. BEOVU should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.
All pregnancies have a background risk of birth defect, loss, and other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.
VEGF inhibition has been shown to cause malformations, embryo-fetal resorption, and decreased fetal weight. VEGF inhibition has also been shown to affect follicular development, corpus luteum function, and fertility.
There is no information regarding the presence of brolucizumab in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production/excretion. Because many drugs are transferred in human milk and because of the potential for absorption and adverse reactions in the breastfed child, breastfeeding is not recommended during treatment and for at least one month after the last dose when stopping treatment with BEOVU.
Females of reproductive potential should use highly effective contraception (methods that result in less than 1% pregnancy rates) during treatment with BEOVU and for at least one month after the last dose when stopping treatment with BEOVU.
No studies on the effects of brolucizumab on fertility have been conducted and it is not known whether brolucizumab can affect reproductive capacity. Based on its anti-VEGF mechanism of action, treatment with BEOVU may pose a risk to reproductive capacity.
The safety and efficacy of BEOVU in pediatric patients has not been established.
In the two Phase 3 clinical studies, approximately 90% (978/1089) of patients randomized to treatment with BEOVU were ≥65 years of age and approximately 60% (648/1089) were ≥75 years of age. No significant differences in efficacy or safety were seen with increasing age in these studies. No dosage regimen adjustment is required in patients 65 years and above.
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