Brolucizumab

FDA Drug Information • Also known as: Beovu

Brand Names: Beovu
Dosage Form: SOLUTION
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION Brolucizumab-dbll is a recombinant human vascular endothelial growth factor inhibitor. Brolucizumab-dbll is a humanized monoclonal single-chain Fv (scFv) antibody fragment. Brolucizumab-dbll has a molecular weight of ~26 kilodaltons and is produced in Escherichia coli cells by recombinant DNA technology. BEOVU (brolucizumab-dbll) injection is a sterile, clear to slightly opalescent, colorless to slightly brownish-yellow solution in a single-dose pre-filled syringe or a single-dose vial for intravitreal administration. Each single-dose pre-filled syringe and vial is designed to deliver 0.05 mL of solution containing 6 mg brolucizumab-dbll, polysorbate 80 (0.02%), sodium citrate (10 mM), sucrose (5.8%), and Water for Injection, USP and with a pH of approximately 7.2. This product does not contain an antimicrobial preservative.

What Is Brolucizumab Used For?

1 INDICATIONS AND USAGE BEOVU ® is indicated for the treatment of: BEOVU is a human vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of: Neovascular (Wet) Age-Related Macular Degeneration (AMD) ( 1.1 ) Diabetic Macular Edema (DME) ( 1.2 ) 1.1 Neovascular (Wet) Age-related Macular Degeneration (AMD) 1.2 Diabetic Macular Edema (DME)

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Neovascular (Wet) Age-Related Macular Degeneration (AMD) 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 three doses, followed by one dose of 6 mg (0.05 mL) every 8-12 weeks ( 2.2 ). Diabetic Macular Edema (DME) The recommended dose for BEOVU is 6 mg (0.05 mL of 120 mg/mL solution) every six weeks (approximately every 39-45 days) for the first five doses, followed by one dose of 6 mg (0.05 mL of 120 mg/mL solution) every 8-12 weeks ( 2.3 ). 2.1 General Dosing Information For ophthalmic intravitreal injection. BEOVU must be administered by a qualified physician. BEOVU is available packaged as follows [see How Supplied/Storage and Handling (16)] : Pre-filled Syringe Vial kit with injection components (vial, filter needle) 2.2 Neovascular (Wet) Age-Related Macular Degeneration (AMD) The recommended dose for BEOVU is 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection monthly (approximately every 25 to 31 days) for the first three doses, followed by 6 mg (0.05 mL) by intravitreal injection once every 8 to 12 weeks. 2.3 Diabetic Macular Edema (DME) The recommended dose for BEOVU is 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection every six weeks (approximately every 39-45 days) for the first five doses, followed by 6 mg (0.05 mL) by intravitreal injection once every 8-12 weeks. 2.4 Preparation for Administration – Pre-filled Syringe and Vial Store BEOVU in the refrigerator between 2°C to 8°C (36°F to 46°F); do not freeze. Keep BEOVU in the outer carton to protect from light. Prior to use, the unopened glass vial or sealed blister pack of BEOVU may be kept at room temperature, 20°C to 25°C (68°F to 77°F) for up to 24 hours. After opening, proceed under aseptic conditions. BEOVU is a clear to slightly opalescent and colorless to slightly brownish-yellow solution. BEOVU should be inspected visually upon removal from the refrigerator and prior to administration. If particulates, cloudiness, or discoloration are visible, the BEOVU must not be used. Use aseptic technique for preparation of the intravitreal injection. Pre-filled Syringe The BEOVU pre-filled glass syringe is sterile and for the treatment of a single eye. It should be inspected visually prior to administration. Do not use if the packaging, or pre-filled syringe are opened, damaged, or expired [see How Supplied/Storage and Handling (16)] . STEP 1: PREPARE Peel the lid off the blister package and, using aseptic technique, remove the sterile syringe. STEP 2: SNAP OFF SYRINGE CAP Snap off the syringe cap and dispose of it (see Figure 1). Do not turn or twist the syringe cap. Figure 1: STEP 3: ATTACH INJECTION NEEDLE Aseptically and firmly assemble a 30-gauge x ½ inch sterile injection needle (not included) onto the Luer lock syringe. STEP 4: DISLODGE AIR BUBBLES To check for air bubbles, hold the syringe with the needle pointing up. If there...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following potentially serious adverse reactions are described elsewhere in the labeling: Hypersensitivity [see Contraindications (4.3)] Endophthalmitis and Retinal Detachment [see Warnings and Precautions (5.1)] Retinal Vasculitis and/or Retinal Vascular Occlusion [see Warnings and Precautions (5.2)] Increase in Intraocular Pressure [see Warnings and Precautions (5.3)] Thromboembolic Events [see Warnings and Precautions (5.4)] The most common adverse reactions reported in patients receiving BEOVU are vision blurred, cataract, conjunctival hemorrhage, eye pain, and vitreous floaters ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience 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 1,646 patients treated with brolucizumab constituted the safety population in four Phase 3 studies. Among these, 1,098 patients were treated with the recommended dose of 6 mg. A total of 1,088 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)] . A total of 558 patients treated with brolucizumab constituted the safety population in the two controlled DME Phase 3 studies (KESTREL and KITE) from baseline to week 52, including 368 patients treated with the recommended dose of 6 mg [see Clinical Studies (14.2)] . Table 1: Common Adverse Reactions (≥ 1%) in the AMD and DME Clinical Trials 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. BEOVU Active Control (aflibercept) Adverse Drug Reactions AMD (N = 730) DME (N = 368) AMD (N = 729) DME (N = 368) Vision blurred a 10% 2% 11% 4% Cataract 7% 4% 11% 5% Conjunctival hemorrhage 6% 6% 7% 7% Vitreous floaters 5% 3% 3% 2% Eye pain 5% 3% 6% 2% Intraocular inflammation b 4% 3% 1% 1% Intraocular pressure increased 4% 2% 5% 1% Retinal hemorrhage 4% 3% 1% Vitreous detachment 4% 2% 3% 1% Conjunctivitis 3% 2% 2% < 1% Retinal pigment epithelial tear 3% 1% Corneal abrasion 2% 1% 2% 2% Hypersensitivity c 2% 1% 1% 1% Punctate keratitis 1% 1% 2% Retinal tear 1% < 1% 1% < 1% Endophthalmitis 1% < 1% < 1% 1% Blindness d 1% < 1% < 1% Retinal artery occlusion 1% 1% < 1% < 1% Retinal detachment 1% < 1% 1% Conjunctival hyperemia 1% < 1% 1% 1% Lacrimation increased 1% < 1% 1% < 1% Abnormal sensation in eye 1% < 1% 2% 1% Detachment of retinal pigment epithelium 1% < 1% Vitreous hemorrhage < 1% 1% < 1% 1% In clinical trials, scleritis and episcleritis were reported (incidence < 1%). 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 two BEOVU doses during maintenance treatment should not be less than 8 weeks. 6.2 Immunogenicity 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...

Contraindications

4 CONTRAINDICATIONS Ocular or Periocular Infections ( 4.1 ) Active Intraocular Inflammation ( 4.2 ) Hypersensitivity ( 4.3 ) 4.1 Ocular or Periocular Infections BEOVU is contraindicated in patients with ocular or periocular infections. 4.2 Active Intraocular Inflammation BEOVU is contraindicated in patients with active intraocular inflammation. 4.3 Hypersensitivity 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.

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of BEOVU administration in pregnant women. In an animal reproduction study, intravitreal administration of brolucizumab to pregnant monkeys once every 4 weeks in one eye from organogenesis to birth did not indicate any harmful effects with respect to pre- or postnatal development at 10-fold the maximum recommended human dose (MRHD) on a mg/kg basis ( see Data ). 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% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data In an enhanced pre- and postnatal development (ePPND) study in pregnant cynomolgus monkeys, brolucizumab was administered to all animals by intravitreal (IVT) injection to one eye at doses of 3 or 6 mg once every 4 weeks until delivery. There was no impact of IVT administration of brolucizumab on embryo-fetal development, pregnancy or parturition; or on the survival, growth, or postnatal development of offspring at 6 mg/eye (10-fold the MRHD on a mg/kg basis). VEGF inhibition has been shown to cause malformations, embryo-fetal resorption, and decreased fetal weight. VEGF also has been shown to affect follicular development, corpus luteum function, and fertility.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied BEOVU (brolucizumab-dbll) injection is supplied as a clear to slightly opalescent and colorless to slightly brownish-yellow solution in a single-dose pre-filled syringe and a single-dose vial. Each pre-filled syringe or vial is for the treatment of a single eye. BEOVU is supplied in the following presentations [see Dosage and Administration (2.3)] . NDC NUMBER CARTON TYPE CARTON CONTENTS 0078-0827-60 Pre-filled Syringe one sealed blister pack containing one BEOVU 6 mg/0.05 mL single-dose pre-filled syringe one Prescribing Information 0078-0827-61 Vial Kit with Injection Components one BEOVU 6 mg/0.05 mL single-dose vial one 18-gauge x 1½ inch, 1.2 mm x 40 mm, 5-micron, filter needle for withdrawal of the contents one Prescribing Information 16.2 Storage and Handling Refrigerate BEOVU between 2°C to 8°C (36°F to 46°F). Do not freeze. Store BEOVU in the outer carton to protect from light. Prior to use, the unopened glass vial or sealed blister pack of BEOVU may be kept at room temperature, 20°C to 25°C (68°F to 77°F) for up to 24 hours.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.