NDC 0078-0827 Beovu


NDC Product Code 0078-0827

NDC 0078-0827-61

Package Description: 1 VIAL, SINGLE-DOSE in 1 CARTON > .05 mL in 1 VIAL, SINGLE-DOSE

NDC 0078-0827-99

Package Description: 1 VIAL, SINGLE-DOSE in 1 CARTON > .05 mL in 1 VIAL, SINGLE-DOSE

NDC Product Information

Beovu with NDC 0078-0827 is a a human prescription drug product labeled by Novartis Pharmaceuticals Corporation. The generic name of Beovu is brolucizumab. The product's dosage form is injection, solution and is administered via intravitreal form.

Labeler Name: Novartis Pharmaceuticals Corporation

Dosage Form: Injection, Solution - A liquid preparation containing one or more drug substances dissolved in a suitable solvent or mixture of mutually miscible solvents that is suitable for injection.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Beovu Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • BROLUCIZUMAB 6 mg/.05mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SUCROSE (UNII: C151H8M554)
  • NITROGEN (UNII: N762921K75)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravitreal - Administration within the vitreous body of the eye.

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Novartis Pharmaceuticals Corporation
Labeler Code: 0078
FDA Application Number: BLA761125 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: BLA - A product marketed under an approved Biologic License Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 10-07-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Beovu Product Label Images

Beovu Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1     Indications And Usage

BEOVU® is indicated for the treatment of Neovascular (Wet) Age-related Macular Degeneration (AMD).

2.1     General Dosing Information

For ophthalmic intravitreal injection. BEOVU must be administered by a qualified physician.

The recommended dose for BEOVU is 6 mg (0.05 mL of 120 mg/mL solution) administered by intravitreal injection monthly (approximately every 25-31 days) for the first three doses, followed by 6 mg (0.05 mL) by intravitreal injection once every 8-12 weeks.

2.3     Preparation For Administration

  • Store BEOVU in the refrigerator between 2 to 8°C (36 to 46°F); do not freeze. Keep the vial in the outer carton to protect from light.Prior to use, the unopened glass vial of BEOVU may be kept at room temperature, 20 to 25°C (68 to 77°F) for up to 24 hours. After opening the glass vial, 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 glass vial must not be used.The BEOVU kit includes the sterile glass vial and filter needle which are for single use only. Do not use if the packaging, vial and/or filter needle are damaged or expired [see How Supplied/Storage and Handling (16)].Use aseptic technique for preparation of the intravitreal injection.STEP 1: Gather the supplies needed.
  • One BEOVU vial (included)One sterile 5-micron blunt filter needle (18-gauge x 1½ inch, 1.2 mm x 40 mm) (included)One sterile 30-gauge x ½ inch injection needle (not included) •  One sterile 1 mL syringe with a 0.05 mL dose mark (not included) •  Alcohol swab (not included)STEP 2Allow vial to come to room temperature and inspect the solution. If particulates, cloudiness, or discoloration are visible, discard the vial and obtain a new vial.STEP 3Remove the vial cap and clean the vial septum (e.g., with alcohol swab).STEP 4Assemble the 5-micron filter needle (18-gauge x 1½ inch) onto a 1-mL syringe using aseptic technique.STEP 5Push the filter needle into the center of the vial septum until the needle touches the bottom of the vial.STEP 6To withdraw the liquid, hold the vial slightly inclined and slowly withdraw all the liquid from the vial and filter needle.Ensure that the plunger rod is drawn sufficiently back when emptying the vial in order to completely empty the filter needle.STEP 7Disconnect the filter needle from the syringe in an aseptic manner and dispose of it. The filter needle is not to be used for the intravitreal injection.STEP 8Aseptically and firmly assemble a 30-gauge x ½ inch injection needle onto the syringe.
  • STEP 9Check for air bubbles by holding the syringe with the needle pointing up. If there are any air bubbles, gently tap the syringe with your finger until the bubbles rise to the top.STEP 10Carefully expel the air from the syringe and adjust the dose to the 0.05 mL mark. The syringe is ready for the injection.

2.4     Injection Procedure

Ensure that the injection is given immediately after preparation of the dose.The intravitreal injection procedure must be carried out under aseptic conditions, which includes the use of surgical hand disinfection, sterile gloves, a sterile drape and a sterile eyelid speculum (or equivalent), and the availability of sterile paracentesis equipment (if required). Adequate anesthesia and a broad-spectrum topical microbicide to disinfect the periocular skin, eyelid, and ocular surface should be administered prior to the injection.Inject slowly until the rubber stopper reaches the end of the syringe to deliver the volume of 0.05 mL. Confirm delivery of the full dose by checking that the rubber stopper has reached the end of the syringe barrel.Immediately following the intravitreal injection, patients should be monitored for elevation in intraocular pressure (IOP). Appropriate monitoring may consist of a check for perfusion of the optic nerve head or tonometry. If required, a sterile paracentesis needle should be available.Following intravitreal injection, patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment (e.g., eye pain, redness of the eye, photophobia, blurring of vision) without delay [see Patient Counseling Information (17)].Each vial should only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new vial should be used and the sterile field, syringe, gloves, drapes, eyelid speculum, filter, and injection needles should be changed before BEOVU is administered to the other eye.Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

3     Dosage Forms And Strengths

Intravitreal Injection: 6 mg/0.05 mL, clear to slightly opalescent and colorless to slightly brownish-yellow solution in a single-dose vial.

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.

5.1     Endophthalmitis And Retinal Detachments

Intravitreal injections, including those with BEOVU, have been associated with endophthalmitis and retinal detachments [see 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)].

5.2     Increase In Intraocular Pressure

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)].

5.3     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 [see Clinical Studies (14.1)].

6     Adverse Reactions

  • The following potentially serious adverse reactions are described elsewhere in the labeling:Hypersensitivity [see Contraindications (4.3)]Endophthalmitis and Retinal Detachments [see Warnings and Precautions (5.1)]Increase in intraocular pressure [see Warnings and Precautions (5.2)]Thromboembolic Events [see Warnings and Precautions (5.3)]

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 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 TrialsaIncluding vision blurred, visual acuity reduced, visual acuity reduced transiently and visual impairment.bIncluding anterior chamber cell, anterior chamber flare, anterior chamber inflammation, chorioretinitis, eye inflammation, iridocyclitis, iritis, uveitis, vitreous haze, vitritis.cIncluding urticaria, rash, pruritus, erythema.dIncluding blindness, blindness transient, amaurosis, and amaurosis fugax.
Adverse Drug ReactionsBEOVU(N = 730)Active Control (aflibercept)(N = 729)Vision blurreda10%11%Cataract7%11%Conjunctival hemorrhage6%7%Vitreous floaters5%3%Eye pain5%6%Intraocular inflammationb4%1%Intraocular pressure increased4%5%Retinal hemorrhage4%3%Vitreous detachment4%3%Conjunctivitis3%2%Retinal pigment epithelial tear3%1%Corneal abrasion2%2%Hypersensitivityc2%1%Punctate keratitis1%2%Retinal tear1%1%Endophthalmitis1%< 1%Blindnessd1%< 1%Retinal artery occlusion1%< 1%Retinal detachment1%< 1%Conjunctival hyperemia1%1%Lacrimation increased1%1%Abnormal sensation in eye1%2%Detachment of retinal pigment epithelium1%< 1%

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 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.

8.1     Pregnancy

Risk SummaryThere 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.DataAnimal DataVEGF 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.

8.2     Lactation

Risk SummaryThere 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.

8.3     Females And Males Of Reproductive Potential

ContraceptionFemalesFemales 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. InfertilityNo 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.

8.4     Pediatric Use

The safety and efficacy of BEOVU in pediatric patients has not been established.

8.5     Geriatric Use

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.

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, preservative-free, clear to slightly opalescent, colorless to slightly brownish-yellow solution in a single-dose vial for intravitreal administration. Each 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.

12.1     Mechanism Of Action

Brolucizumab is a human VEGF inhibitor. Brolucizumab binds to the three major isoforms of VEGF-A (e.g., VEGF110, VEGF121, and VEGF165), thereby preventing interaction with receptors VEGFR-1 and VEGFR-2. By inhibiting VEGF-A, brolucizumab suppresses endothelial cell proliferation, neovascularization, and vascular permeability.

12.2     Pharmacodynamics

Leakage of blood and fluid from choroidal neovascularization (CNV) may cause retinal thickening or edema. Reductions in central retinal subfield thickness (CST) were observed across all treatment arms.

12.3     Pharmacokinetics

Following a single intravitreal dose of 6 mg BEOVU to 25 AMD patients, the mean (range) serum Cmax of free brolucizumab (unbound to VEGF-A) was 49 ng/mL (9 to 548 ng/mL) and was attained at 24 hours post-dose. Brolucizumab concentrations were near or less than 0.5 ng/mL (lower limit of assay quantitation) at approximately 4 weeks after repeat dose administration and no accumulation in serum was observed in most patients.Elimination The estimated mean (± standard deviation) systemic half-life of brolucizumab is 4.4 days (± 2.0 days) after a single intravitreal dose.MetabolismMetabolism of brolucizumab has not been fully characterized. However, free brolucizumab is expected to undergo metabolism via proteolysis.ExcretionThe excretion of brolucizumab has not been fully characterized. However, free brolucizumab is expected to undergo target-mediated disposition and/or passive renal excretion.Specific PopulationsFollowing repeat intravitreal dose administration of 6 mg BEOVU, no differences in the systemic pharmacokinetics of brolucizumab were observed based on age (50 years and above), sex, or mild to moderate renal impairment (glomerular filtration rate (GFR) = 30 to 70 mL/min, estimated using the Modification of Diet in Renal Disease (MDRD) equation). The effect of severe renal impairment or any degree of hepatic impairment on the pharmacokinetics of BEOVU is unknown. As significant increases in serum brolucizumab exposures are not expected with intravitreal route of administration, no dosage adjustment is needed based on renal or hepatic impairment status.Drug Interaction StudiesNo studies evaluating the drug interaction potential of BEOVU have been conducted.

13.1     Carcinogenesis, Mutagenesis, Impairment Of Fertility

No studies have been conducted on the carcinogenic or mutagenic potential of BEOVU. Based on the anti-VEGF mechanism of action, treatment with BEOVU may pose a risk to reproductive capacity [see Use in Specific Populations (8.3)].

The safety and efficacy of BEOVU were assessed in two randomized, multi-center, double-masked, active-controlled studies (HAWK - NCT02307682 and HARRIER - NCT02434328) in patients with neovascular AMD. A total of 1817 patients were treated in these studies for two years (1088 on brolucizumab and 729 on control). Patient ages ranged from 50 to 97 years with a mean of 76 years.In HAWK, patients were randomized in a 1:1:1 ratio to the following dosing regimens:     1) brolucizumab 3 mg administered every 8 or 12 weeks after the first 3 monthly doses,     2) brolucizumab 6 mg administered every 8 or 12 weeks after the first 3 monthly doses,     3) aflibercept 2 mg administered every 8 weeks after the first 3 monthly doses.In HARRIER, patients were randomized in a 1:1 ratio to the following dosing regimens:     1) brolucizumab 6 mg administered every 8 or 12 weeks after the first 3 monthly doses,     2) aflibercept 2 mg administered every 8 weeks after the first 3 monthly doses.In both studies, after three initial monthly doses (Week 0, 4, and 8), treating physicians decided whether to treat each individual patient on an every 8 week or 12 week dosing interval guided by visual and anatomical measures of disease activity, although the utility of these measures has not been established. Patients on 12 week dosing intervals could be changed based on the same measures to an 8 week schedule after subsequent treatment visits. Any patient placed on an 8 week schedule, remained on the 8 week dosing interval until the end of the study. Protocol-specified visits in the initial three months occurred every 28 ± 3 days followed by every 28 ± 7 days for the remainder of the studies. Baseline anatomical measures may have contributed to the regimen selection because the majority of patients on the 12-week dosing schedule at the end of the trial had less baseline macular edema and/or smaller baseline lesions.Both studies demonstrated efficacy in the primary endpoint defined as the change from baseline in Best Corrected Visual Acuity (BCVA) at Week 48, measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score. In both studies, BEOVU treated patients had a similar mean change from baseline in BCVA as the patients treated with aflibercept 2 mg (fixed every 8 weeks). Detailed results of both studies are shown in Table 2 and Figures 5 and 6 below.Table 2: Efficacy Outcomes at Week 48 and 96 in Phase 3 HAWK and HARRIER StudiesAbbreviations - BCVA: Best Corrected Visual Acuity; missing data are imputed using last observation carried forward (LOCF) method, ETDRS: Early Treatment Diabetic Retinopathy Study, SE: standard error.  HAWK HARRIEREfficacy outcome
At weekBEOVU (n = 360)
Aflibercept2 mg(n = 360)
Difference(95% CI)brolucizumab – afliberceptBEOVU (n = 370)
Aflibercept2 mg(n = 369)
Difference(95% CI)brolucizumab – afliberceptMean (SD) BCVA at Baseline60.8 (13.7)
60.0 (13.9)61.5 (12.6)60.8 (12.9)
Mean (SE) change from baseline in BCVA (measured by ETDRS letters score)48



-0.2(-2.1, 1.8)

+0.5(-1.6, 2.7)


-0.7(-2.4, 1.0)

-0.4(-2.5, 1.6)
Proportion of patients who gained visual acuity (%) (≥ 15 letters of BCVA)48

278.2(2.2, 15.0)

7.2(1.4, 13.8)
31.5-0.6(-7.1, 5.8)

-2.4(-8.8, 4.1)
Proportion of patients who lost visual acuity (%) (≥ 15 letters of BCVA)48

7.40.9(-2.7, 4.3)

0.7(-3.6, 4.6)
7.5-1.0(-3.9, 2.2)

-0.4(-3.8, 3.3)
Figure 5: Mean Change in Visual Acuity From Baseline to Week 96 in HAWKFigure 6: Mean Change in Visual Acuity From Baseline to Week 96 in HARRIERThrough Week 48, 56% (HAWK) and 51% (HARRIER) of patients remained on BEOVU every 12 weeks. The proportion of patients who were maintained on every 12 week dosing through Week 96 was 45% and 39% in HAWK and HARRIER, respectively. The probability of remaining on every 12 week dosing from Week 20 to Week 48 was 85% and 82%, and from Week 48 to Week 96 was 82% and 75% in HAWK and HARRIER, respectively.Treatment effects in evaluable subgroups (e.g., age, gender, race, baseline visual acuity) in each study were generally consistent with the results in the overall populations.

16.1     How Supplied

BEOVU (brolucizumab-dbll) injection is supplied as a clear to slightly opalescent and colorless to slightly brownish-yellow 6 mg/0.05 mL solution in a single-dose vial. Each BEOVU carton (NDC 0078-0827-61) contains one BEOVU vial and one sterile 5 µm blunt filter needle (18-gauge x 1½ inch, 1.2 mm x 40 mm).

16.2     Storage And Handling

Refrigerate BEOVU between 2 to 8°C (36 to 46°F). Do not freeze. Store the vial in the outer carton to protect from light.Prior to use, the unopened glass vial of BEOVU may be kept at room temperature, 20 to 25°C (68 to 77°F) for up to 24 hours.

17     Patient Counseling Information

Endophthalmitis and Retinal DetachmentsAdvise patients that in the days following BEOVU administration, patients are at risk of developing endophthalmitis. If the eye becomes red, sensitive to light, painful, or develops a change in vision, advise the patient to seek immediate care from an ophthalmologist [see Warnings and Precautions (5.1)].Patients may experience temporary visual disturbances after an intravitreal injection with BEOVU and the associated eye examination [see Adverse Reactions (6.1)]. Advise patients not to drive or use machinery until visual function has recovered sufficiently.Manufactured by:Novartis Pharmaceuticals CorporationEast Hanover, New Jersey 07936U.S. License Number: 1244© NovartisT2019-105

* Please review the disclaimer below.