Vascular Endothelial Growth Factor Inhibitor

Byooviz

Approved 17 Sept 2021InjectionInjectable

Indications

BYOOVIZ is indicated for the treatment of patients with: BYOOVIZ, a vascular endothelial growth factor (VEGF) inhibitor, is indicated for the treatment of patients with: Neovascular (Wet) Age-Related Macular Degeneration (AMD) ( 1.1 ) Macular Edema Following Retinal Vein Occlusion (RVO) ( 1.2 ) Myopic Choroidal Neovascularization (mCNV) ( 1.3 )

1.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD)

1.2 Macular Edema Following Retinal Vein Occlusion (RVO)

1.3 Myopic Choroidal Neovascularization (mCNV)

Contraindications

Ocular or periocular infections ( 4.1 ) Hypersensitivity ( 4.2 )

4.1Ocular or Periocular Infections

BYOOVIZ is contraindicated in patients with ocular or periocular infections.

4.2Hypersensitivity

BYOOVIZ is contraindicated in patients with known hypersensitivity to ranibizumab products or any of the excipients in BYOOVIZ. Hypersensitivity reactions may manifest as severe intraocular inflammation.

Warnings and precautions

Endophthalmitis and retinal detachments may occur following intravitreal injections. Patients should be monitored following the injection ( 5.1 ). Increases in intraocular pressure (IOP) have been noted both pre- and post-intravitreal injection ( 5.2 ). There is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors ( 5.3 ).

5.1Endophthalmitis and Retinal Detachments

Vascular Endothelial Growth Factor Inhibitor

Byooviz

Approved 17 Sept 2021InjectionInjectable

Official labelAsk Osler about it

Indications

1.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD)

1.2 Macular Edema Following Retinal Vein Occlusion (RVO)

1.3 Myopic Choroidal Neovascularization (mCNV)

Contraindications

Ocular or periocular infections ( 4.1 ) Hypersensitivity ( 4.2 )

4.1Ocular or Periocular Infections

BYOOVIZ is contraindicated in patients with ocular or periocular infections.

4.2Hypersensitivity

Warnings and precautions

5.1Endophthalmitis and Retinal Detachments

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

There are no adequate and well-controlled studies of ranibizumab products administered in pregnant women. Administration of ranibizumab to pregnant monkeys throughout the period of organogenesis resulted in a low incidence of skeletal abnormalities at intravitreal doses 13-times the predicted human exposure (based on maximal serum trough levels [C max ]) after a single eye treatment at the recommended clinical dose. No skeletal abnormalities were observed at serum trough levels equivalent to the predicted human exposure after a single eye treatment at the recommended clinical dose [ see Animal Data ].

Animal reproduction studies are not always predictive of human response, and it is not known whether ranibizumab products can cause fetal harm when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for ranibizumab products [ see Clinical Pharmacology (12.1) ], treatment with ranibizumab products may pose a risk to human embryofetal development. BYOOVIZ should be given to a pregnant woman only if clearly needed.

Data Animal Data An embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received intravitreal injections of ranibizumab every 14 days starting on Day 20 of gestation, until Day 62 at doses of 0, 0.125, and 1 mg/eye. Skeletal abnormalities including incomplete and/or irregular ossification of bones in the skull, vertebral column, and hindlimbs and shortened supernumerary ribs were seen at a low incidence in fetuses from animals treated with 1 mg/eye of ranibizumab.

The 1 mg/eye dose resulted in trough serum ranibizumab levels up to 13 times higher than predicted Cmax levels with single eye treatment in humans. No skeletal abnormalities were seen at the lower dose of 0.125 mg/eye, a dose which resulted in trough exposures equivalent to single eye treatment in humans. No effect on the weight or structure of the placenta, maternal toxicity, or embryotoxicity was observed.

Adverse reactions

The following adverse reactions are discussed in greater detail in other sections of the label: Endophthalmitis and Retinal Detachments [ see Warnings and Precautions (5.1) ] Increases in Intraocular Pressure [ see Warnings and Precautions (5.2) ] Thromboembolic Events [ see Warnings and Precautions (5.3) ] The most common adverse reactions (reported more frequently in ranibizumab treated subjects than control subjects) are conjunctival hemorrhage, eye pain, vitreous floaters, and increased IOP ( 6.2 ).

To report SUSPECTED ADVERSE REACTIONS, contact Harrow Eye, LLC™ at 1-833-442-7769 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Injection Procedure

Serious adverse reactions related to the injection procedure have occurred in < 0.1% of intravitreal injections, including endophthalmitis [ see Warnings and Precautions (5.1) ], rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.

6.2Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of the same or another drug and may not reflect the rates observed in practice. The data below reflect exposure to 0.5 mg ranibizumab in 440 patients with neovascular AMD in Studies AMD-1, AMD-2, and AMD-3; in 259 patients with macular edema following RVO.

Safety data observed in 224 patients with mCNV, as well as Studies AMD-4 and D-3, were consistent with these results. On average, the rates and types of adverse reactions in patients were not significantly affected by dosing regimen. Ocular Reactions Table 1 shows frequently reported ocular adverse reactions in ranibizumab-treated patients compared with the control group. Table 1 Ocular Reactions in the AMD, and RVO Studies Adverse Reaction AMD 2-year AMD 1-year RVO 6-month Ranibizumab 0.5 mg Control Ranibizumab 0.5 mg Control Ranibizumab 0.5 mg Control n=379 n=379 n=440 n=441 n=259 n=260 Conjunctival hemorrhage 74% 60% 64% 50% 48% 37% Eye pain 35% 30% 26% 20% 17% 12% Vitreous floaters 27% 8% 19% 5% 7% 2% Intraocular pressure increased 24% 7% 17% 5% 7% 2% Vitreous detachment 21% 19% 15% 15% 4% 2% Intraocular inflammation 18% 8% 13% 7% 1% 3% Cataract 17% 14% 11% 9% 2% 2% Foreign body sensation in eyes 16% 14% 13% 10% 7% 5% Eye irritation 15% 15% 13% 12% 7% 6% Lacrimation increased 14% 12% 8% 8% 2% 3% Blepharitis 12% 8% 8% 5% 0% 1% Dry eye 12% 7% 7% 7% 3% 3% Visual disturbance or vision blurred 18% 15% 13% 10% 5% 3% Eye pruritis 12% 11% 9% 7% 1% 2% Ocular hyperemia 11% 8% 7% 4% 5% 3% Retinal disorder 10% 7% 8% 4% 2% 1% Maculopathy 9% 9% 6% 6% 11% 7% Retinal degeneration 8% 6% 5% 3% 1% 0% Ocular discomfort 7% 4% 5% 2% 2% 2% Conjunctival hyperemia 7% 6% 5% 4% 0% 0% Posterior capsule opacification 7% 4% 2% 2% 0% 1% Injection site hemorrhage 5% 2% 3% 1% 0% 0% Non-Ocular Reactions Non-ocular adverse reactions with an incidence of ≥ 5% in patients receiving ranibizumab for AMD, and/or RVO and which occurred at a ≥ 1% higher frequency in patients treated with ranibizumab compared to control are shown in Table 2.

Though less common, wound healing complications were also observed in some studies. Table 2 Non-Ocular Reactions in the AMD, and RVO Studies Adverse Reaction AMD 2-year AMD 1-year RVO 6-month Ranibizumab 0.5 mg Control Ranibizumab 0.5 mg Control Ranibizumab 0.5 mg Control n=379 n=379 n=440 n=441 n=259 n=260 Nasopharyngitis 16% 13% 8% 9% 5% 4% Anemia 8% 7% 4% 3% 1% 1% Nausea 9% 6% 5% 5% 1% 2% Cough 9% 8% 5% 4% 1% 2% Constipation 5% 7% 3% 4% 0% 1% Seasonal allergy 4% 4% 2% 2% 0% 2% Hypercholesterolemia 5% 5% 3% 2% 1% 1% Influenza 7% 5% 3% 2% 3% 2% Renal failure 1% 1% 0% 0% 0% 0% Upper respiratory tract infection 9% 8% 5% 5% 2% 2% Gastroesophageal reflux disease 4% 6% 3% 4% 1% 0% Headache 12% 9% 6% 5% 3% 3% Edema peripheral 3% 5% 2% 3% 0% 1% Renal failure chronic 0% 1% 0% 0% 0% 0% Neuropathy peripheral 1% 1% 1% 0% 0% 0% Sinusitis 8% 7% 5% 5% 3% 2% Bronchitis 11% 9% 6% 5% 0% 2% Atrial fibrillation 5% 4% 2% 2% 1% 0% Arthralgia 11% 9% 5% 5% 2% 1% Chronic obstructive pulmonary disease 6% 3% 3% 1% 0% 0% Wound healing complications 1% 1% 1% 0% 0% 0%

6.3Immunogenicity

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of ranibizumab or of other ranibizumab products. The pre-treatment incidence of immunoreactivity to ranibizumab was 0%-5% across treatment groups.

After monthly dosing with ranibizumab for 6 to 24 months, antibodies to ranibizumab were detected in approximately 1%-9% of patients. The clinical significance of immunoreactivity to ranibizumab products are unclear at this time. Among neovascular AMD patients with the highest levels of immunoreactivity, some were noted to have iritis or vitritis. Intraocular inflammation was not observed in patients with RVO patients with the highest levels of immunoreactivity.

6.4Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ranibizumab products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Ocular: Tear of retinal pigment epithelium among patients with neovascular AMD

Byooviz

Indications

Contraindications

4.1Ocular or Periocular Infections

4.2Hypersensitivity

Warnings and precautions

5.1Endophthalmitis and Retinal Detachments

Two medicines in one question?

Byooviz

Indications

Contraindications

4.1Ocular or Periocular Infections

4.2Hypersensitivity

Warnings and precautions

5.1Endophthalmitis and Retinal Detachments

Two medicines in one question?

5.2Increases in Intraocular Pressure Increases

5.3Thromboembolic Events

5.4Retinal Vasculitis with or without Occlusion

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Injection Procedure

6.2Clinical Trials Experience

6.3Immunogenicity

6.4Postmarketing Experience

Composition

Official product information

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