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Byooviz ranibizumab-nuna 10 mg/mL Injection, Solution, 1 vial — NDC 64406-0019-01 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Byooviz ranibizumab-nuna 10 mg/mL Injection, Solution, 1 vial — NDC 64406-019-01 (Billing 64406-0019-01)

by BIOGEN INC. · 1 VIAL, SINGLE-DOSE in 1 CARTON / .05 mL in 1 VIAL, SINGLE-DOSE

This is a package of 1 vial of Byooviz ranibizumab-nuna 10 mg/mL Injection, Solution from BIOGEN INC., marketed since Jun 2022 and currently FDA-listed, this package's marketing is listed to end Jul 2028. It is the main listing for this product, which comes in 2 package sizes.

NDC 64406-0019-01
🏷️ FDA NDC (as labeled) 64406-019-01 billing pads the product segment with a zero
This package
Contains1 vial Medicaid pays$9,934.17 / unit · 12 mo Per package$496.71 / 0.05 ml · Medicaid Pack sizes2 compare ↓
Main listing for product 64406-019 · Also comes in: 1 vial 64406-019-08
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 64406-019-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
64406 labeler · 019 product · 01 package
Package marketed since
Jun 1, 2022
Package marketing ended
Jul 19, 2028
Sample package
No — commercial package
Barcode (UPC-A, from the NDC)
3 6440601901 2
Medicaid fills, this package
419 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 64406-019-01
Product NDC 64406-019
11-digit billing NDC 64406001901
NCPDP billing unit ML — per mL (volume)
RxCUI 2602353, 2602359
UNII ZL1R02VT79
Application # BLA761202
SPL Set ID e46db299-edd1-4457-89b2-c1e2e505f1b0
Established class (EPC) Vascular Endothelial Growth Factor Inhibitor
Mechanism of action Vascular Endothelial Growth Factor Inhibitors
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-06-01
Marketing end 2028-07-19
Route INTRAVITREAL
Dosage form INJECTION, SOLUTION
Substance RANIBIZUMAB
Biologic (Purple Book) 351(k) Interchangeable · interchangeable biosimilar
Reference product ranibizumab

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 86655060502020
GPI class Byooviz
GCN Seq No 082681
GCN 51027
HICL code 047583
Ingredient (HICL) Ranibizumab-Nuna
HIC1 code Q
Therapeutic class — broad (HIC1) Ear/Eye/Nose/Rectum/Topical/Vagina/Other
HIC2 code Q2
Therapeutic class — intermediate (HIC2) Drugs Acting On The Eye
HIC3 code Q2F
Therapeutic class — specific (HIC3) Ophth. Vegf-A Receptor Antag. Rcmb Mc Antibody
AHFS code 52:92.00.00
AHFS class Eent Drugs, Miscellaneous
FDB label name BYOOVIZ 0.5 MG/0.05 ML VIAL
FDB brand name Byooviz
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 082681
  • GCN: 51027
  • GPI-14 (Medi-Span): 86655060502020
  • HICL (First Databank): 047583
  • AHFS class code: 52:92.00.00
  • RxCUI (RxNorm): 2602353
Why two NDCs? The FDA registers this code as 64406-019-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 64406-0019-01. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Vascular Endothelial Growth Factor Inhibitor class.

Pharmacologic class Vascular Endothelial Growth Factor Inhibitor
Drug family (ATC) Antineovascularisation agents
How it works Vascular Endothelial Growth Factor Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name BYOOVIZ 0.5 MG/0.05 ML VIAL Ingredient Ranibizumab-Nuna
📖 What it is MedlinePlus · NLM

Ranibizumab implant is used to treat wet age-related macular degeneration (AMD; an eye disease that causes central vision loss [ability to see straight ahead]), diabetic macular edema (an eye disease caused by diabetes that can lead to vision loss) and diabetic retinopathy (damage to the eyes caused by diabetes). Ranibizumab is in a class of medications called vascular endothelial growth factor A (VEGF-A) antagonists. It works by stopping abnormal blood vessel growth and leakage in the eye(s) that may cause vision loss.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It treats retinal diseases. Susvimo, the implant form, is used for wet AMD, diabetic macular edema and diabetic retinopathy. It is for people who already responded to at least two...
  • An eye specialist gives it inside the eye. With Susvimo, a small implant is surgically placed in your eye and refilled about every 6 months (AMD and DME) or about every 9 months (D...
  • Eye effects are most common. These include bleeding on the white of the eye, eye pain, floaters, higher eye pressure and blurred vision. Call right away for worsening pain, redness...
  • The implant carries a higher risk of a serious eye infection called endophthalmitis than monthly injections. Many cases involved the eye’s surface covering wearing away or pulling...
📖 Read our full Ranibizumab Injection guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $9,934.17 $496.71 / 0.05 ml
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · Q5124 $240.972 / Q5124 unit —
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Billing & reimbursement

FDA NDC (as labeled)64406-019-01
11-digit billing NDC64406-0019-01
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeQ5124
DescriptorInjection, ranibizumab-nuna, biosimilar, (byooviz), 0.1 mg
Billing units / pkg5 units
How the units are derivedThis package is 0.05; the HCPCS unit is 0.1 MG, so one package = 5 billing units.
Medicare Part B spend (2026 (Q1))$34,511 · 109 claims · $316.62 per claim (all NDCs under Q5124)
Crosswalk sourceCMS ASP NDC-HCPCS Crosswalk
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
64406-0019-01 You're viewing this Main listing 1 VIAL, SINGLE-DOSE in 1 CARTON / .05 mL in 1 VIAL, SINGLE-DOSE 2022-06-01 Jul 19, 2028 Active
64406-0019-08 64406-019-08 1 VIAL, SINGLE-DOSE in 1 CARTON / .05 mL in 1 VIAL, SINGLE-DOSE 2022-10-03 Jul 19, 2028 Active

In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in this package?
This package contains 1 vial — 1 vial, single-dose in 1 carton / .05 ml in 1 vial, single-dose.
How does this package differ from NDC 64406-0019-08?
Both are Byooviz ranibizumab-nuna 10 mg/mL Injection, Solution — the drug itself is identical. This page's package is the 1 vial one, while NDC 64406-0019-08 is the 1 vial package.
What NDC number is used to bill for this package of Byooviz ranibizumab-nuna 10 mg/mL Injection, Solution?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Byooviz 10 mg/mLthis 64406-0019-01 BIOGEN 1 vial — — FDA listed —
Byooviz 10 mg/mL 82667-0018-05 Harrow 1 vial — — FDA listed —
About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & biosimilar status

🏛️
2021
First FDA approval
Sep 2021
📍
2026
Currently FDA-listed
5 years listed
🔓
2026
Biosimilars listed
3 FDA-licensed
🧬FDA-licensed biosimilars listed

3 interchangeables are FDA-licensed for this reference biologic — see the list below. (Biologics have no small-molecule generics.)

🛡️ Latest patent/protection date listed: Biosimilars are already FDA-licensed for this product — the last listed patent runs to Sep 2033.
📅 FDA approved Sep 17, 2021

Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.

FDA Purple Book — biosimilars & interchangeables ⓘ
Reference product
Lucentisranibizumab Susvimoranibizumab
Interchangeable 3
Byoovizranibizumab-nuna Cimerliranibizumab-eqrn Nufymcoranibizumab-leyk
Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.
Patents & exclusivity — FDA Purple Book
Exclusivity RefProduct
2021 2023 2025 2027 2029 2031 2033
Today
LOE
Biologic patent Exclusivity
🏛️Reference-product exclusivity
A flat 12 years of FDA market protection from first licensure. No biosimilar can be licensed before it ends — regardless of patents.
🧪Listed biologic patents
Patents the reference maker lists covering the molecule, formulation, or manufacturing. A biosimilar generally can’t launch until these resolve.
🔁Interchangeability
An interchangeable biosimilar may be substituted at the pharmacy (state laws vary). The first one can earn its own exclusivity period.
🛈 What do these terms mean?
Biologic patent
A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
Reference-product exclusivity
A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
Interchangeable exclusivity
The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
Earliest biosimilar (LOE)
The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.

Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.

FDA exclusivity
CodeWhat it grantsExpires
RefProductReference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this dateSep 17, 2033
Common questions
Is there a biosimilar for BYOOVIZ 0.5 MG/0.05 ML VIAL?
Yes — at least one FDA-licensed biosimilar is listed for this biologic. See the Purple Book family above for the available products.
Why do different websites show different biosimilar dates?
Biosimilar availability isn’t based on one single date. Some sources use the reference-product exclusivity, some use the last listed patent, and patent litigation, settlements, and licenses can all change the real-world launch date. This page shows the underlying Purple Book dates so you can see why estimates differ.
Can a biosimilar launch before the last patent expires?
Sometimes. A biosimilar maker may settle with the reference manufacturer or receive a license to launch earlier. In other cases, the last listed protection delays competition.
What does “current Purple Book estimate” mean?
It means we’re using the latest patent and exclusivity dates currently listed in the FDA Purple Book. It is not a guaranteed launch date.
What does “FDA listed” mean?
It means the product appears in the FDA’s official directory. That’s a good sign a product exists for the U.S. market, but on its own it does not confirm a pharmacy can get it today. Where we have recent retail pricing data, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Purple Book for a patent or exclusivity on the reference biologic. It can affect when a biosimilar becomes widely available — but it is not a guaranteed launch date. Settlements and licenses can move the real date earlier or later.
Built from the FDA Purple Book Patent List (patents the reference-product sponsor has publicly listed under the BPCIA) plus reference-product exclusivity. Biosimilars cannot launch until these clear; patent litigation and settlements can shift the real date. Biologics have no small-molecule generics — competition comes from FDA-licensed biosimilars, not the Orange Book.
Where does this data come from?
Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

🧪 Avoiding an ingredient? See Ranibizumab Injection inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 4QD397987E
    An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
  • UNII 1D5Q932XM6
    An amino acid salt used in medicines as a buffer and pH regulator. It helps maintain the proper acidity level in liquid formulations to keep the drug stable and effective.
  • UNII 7T1F30V5YH
    A synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together and keeps them from separating in liquid formulations.
  • UNII 7YIN7J07X4
    A natural sugar derived from plants and microorganisms. It acts as a filler to give the medication bulk and stability, and helps preserve the active ingredient during storage and manufacturing.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

5 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerBIOGEN INC.
FDA applicationBLA761202 (BLA)
Labeler code64406
First marketedJun 2022
Product typeHuman Prescription Drug
Portfolio47 products on file

More NDCs from BIOGEN INC. labeler code 64406

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 75 words ▾

1 INDICATIONS AND USAGE 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)

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION For ophthalmic intravitreal injection only ( 2.1 ) Neovascular (Wet) Age-Related Macular Degeneration (AMD) ( 2.2 ) : BYOOVIZ 0.5 mg (0.05 mL) is recommended to be administered by intravitreal injection once a month (approximately 28 days). Although not as effective, patients may be treated with 3 monthly doses followed by less frequent dosing with regular assessment. Although not as effective, patients may also be treated with one dose every 3 months after 4 monthly doses.

Patients should be assessed regularly. Macular Edema Following Retinal Vein Occlusion (RVO) ( 2.3 ) : BYOOVIZ 0.5 mg (0.05 mL) is recommended to be administered by intravitreal injection once a month (approximately 28 days). Myopic Choroidal Neovascularization (mCNV) ( 2.4 ) : BYOOVIZ 0.5 mg (0.05 mL) is recommended to be initially administered by intravitreal injection once a month (approximately 28 days) for up to three months.

Patients may be retreated if needed.

2.1General Dosing Information FOR OPHTHALMIC INTRAVITREAL INJECTION. Vials: A 5-micron sterile filter needle (18-gauge × 1-1/2 inch or 19-gauge × 1-1/2 inch), a 1-mL Luer lock syringe and a 30- gauge × ½ inch sterile injection needle are needed but not included.

2.2Neovascular (Wet) Age-Related Macular Degeneration (AMD) BYOOVIZ 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days). Although not as effective, patients may be treated with 3 monthly doses followed by less frequent dosing with regular assessment. In the 9 months after three initial monthly doses, less frequent dosing with 4-5 doses on average is expected to maintain visual acuity while monthly dosing may be expected to result in an additional average 1-2 letter gain.

Patients should be assessed regularly [ see Clinical Studies (14.1) ]. Although not as effective, patients may also be treated with one dose every 3 months after 4 monthly doses. Compared with continued monthly dosing, dosing every 3 months over the next 9 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average.

Patients should be assessed regularly [ see Clinical Studies (14.1) ].

2.3Macular Edema Following Retinal Vein Occlusion (RVO) BYOOVIZ 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days). In Studies RVO-1 and RVO-2, patients received monthly injections of ranibizumab for 6 months. In spite of being guided by optical coherence tomography and visual acuity re-treatment criteria, patients who were then not treated at Month 6 experienced on average, a loss of visual acuity at Month 7, whereas patients who were treated at Month 6 did not.

Patients should be treated monthly [ see Clinical Studies (14.2) ].

2.4Myopic Choroidal Neovascularization (mCNV) BYOOVIZ 0.5 mg (0.05 mL of 10 mg/mL BYOOVIZ solution) is recommended to be initially administered by intravitreal injection once a month (approximately 28 days) for up to 3 months. Patients may be retreated if needed [ see Clinical Studies (14.3) ].

2.5Preparation for Administration Vial: Using aseptic technique, all of the BYOOVIZ vial contents are withdrawn through a 5-micron (19- gauge × 1-1/2 inch), sterile filter needle attached to a 1 mL syringe (not included). The filter needle should be discarded after withdrawal of the vial contents and should not be used for intravitreal injection. The filter needle should be replaced with a sterile 30-gauge × ½ inch needle for the intravitreal injection.

Use aseptic technique to carry out the following preparation steps: Prepare for intravitreal injection with the following medical devices for single use (not included): a 5-micron sterile filter needle (18-gauge × 1-1/2 inch or 19-gauge × 1-1/2 inch) a 1 mL sterile Luer lock syringe (with marking to measure 0.05 mL) a sterile injection needle (30-gauge × 1/2-inch) Before withdrawal, disinfect t… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 45 words ▾

3 DOSAGE FORMS AND STRENGTHS Single-dose glass vial designed to provide 0.05 mL for intravitreal injection. Clear to slightly opalescent and colorless to pale yellow, 10 mg/mL solution. Single-dose glass vial designed to provide 0.05 mL for intravitreal injections: 10 mg/mL solution. ( 3 )

⛔ Contraindications 56 words ▾

4 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 Cautions ~3 min read ▾

5 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 Intravitreal injections, including those with ranibizumab products, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique should always be used when administering BYOOVIZ. In addition, patients should be monitored following the injection to permit early treatment should an infection occur [ see Dosage and Administration (2.5 , 2.6) and Patient Counseling Information (17) ].

5.2Increases in Intraocular Pressure Increases in intraocular pressure have been noted both pre-injection and post-injection (at 60 minutes) while being treated with ranibizumab products. Monitor intraocular pressure prior to and following intravitreal injection with BYOOVIZ and manage appropriately [ see Dosage and Administration (2.6) ].

5.3Thromboembolic Events Although there was a low rate of arterial thromboembolic events (ATEs) observed in the ranibizumab 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). Neovascular (Wet) Age-Related Macular Degeneration The ATE rate in the three controlled neovascular AMD studies (AMD-1, AMD-2, AMD-3) during the first year was 1.9% (17 of 874) in the combined group of patients treated with 0.3 mg or 0.5 mg ranibizumab compared with 1.1% (5 of 441) in patients from the control arms [ see Clinical Studies (14.1) ].

In the second year of Studies AMD-1 and AMD-2, the ATE rate was 2.6% (19 of 721) in the combined group of ranibizumab-treated patients compared with 2.9% (10 of 344) in patients from the control arms. In Study AMD-4, the ATE rates observed in the 0.5 mg arms during the first and second year were similar to rates observed in Studies AMD-1, AMD-2, and AMD-3. In a pooled analysis of 2-year controlled studies [AMD-1, AMD-2, and a study of ranibizumab used adjunctively with verteporfin photodynamic therapy (PDT)], the stroke rate (including both ischemic and hemorrhagic stroke) was 2.7% (13 of 484) in patients treated with 0.5 mg ranibizumab compared to 1.1% (5 of 435) in patients in the control arms [odds ratio 2.2 (95% confidence interval (0.8-7.1)].

Macular Edema Following Retinal Vein Occlusion The ATE rate in the two controlled RVO studies during the first 6 months was 0.8% in both the ranibizumab and control arms of the studies (4 of 525 in the combined group of patients treated with 0.3 mg or 0.5 mg ranibizumab and 2 of 260 in the control arms) [ see Clinical Studies (14.2) ]. The stroke rate was 0.2% (1 of 525) in the combined group of ranibizumab -treated patients compared to 0.4% (1 of 260) in the control arms.

5.4Retinal Vasculitis with or without Occlusion Retinal vasculitis with or without occlusion, typically in the presence of preexisting intraocular inflammation or post-treatment with other intravitreal agents, have been reported with the use of ranibizumab products. Discontinue treatment with BYOOVIZ in patients who develop these events. Patients should be instructed to report any change in vision without delay [ see Patient Counseling Information (17) ].

🤒 Adverse Reactions ~3 min read ▾

6 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 Biogen Inc. at 1-877-422-8360 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%… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 55 words ▾

7 DRUG INTERACTIONS Drug interaction studies have not been conducted with ranibizumab products. Ranibizumab intravitreal injection has been used adjunctively with Photodynamic Therapy (PDT). Twelve of 105 (11%) patients with neovascular AMD developed serious intraocular inflammation; in 10 of the 12 patients, this occurred when ranibizumab was administered 7 days (± 2 days) after PDT.

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS

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.

8.2Lactation Risk Summary There are no data available on the presence of ranibizumab products in human milk, the effects of ranibizumab products on the breastfed infant or the effects of ranibizumab products on milk production/excretion. Because many drugs are excreted in human milk, and because the potential for absorption and harm to infant growth and development exists, caution should be exercised when BYOOVIZ is administered to a nursing woman. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for BYOOVIZ and any potential adverse effects on the breastfed child from BYOOVIZ.

8.3Females and Males of Reproductive Potential Infertility No studies on the effects of ranibizumab products on fertility have been conducted and it is not known whether ranibizumab products can affect reproduction capacity. Based on the anti-VEGF mechanism of action for ranibizumab products, treatment with ranibizumab products may pose a risk to reproductive capacity.

8.4Pediatric Use The safety and effectiveness of BYOOVIZ in pediatric patients have not been established.

8.5Geriatric Use In the clinical studies, approximately 76% (2449 of 3227) of patients randomized to treatment with ranibizumab were ≥ 65 years of age and approximately 51% (1644 of 3227) were ≥ 75 years of age [ see Clinical Studies (14) ]. No notable differences in efficacy or safety were seen with increasing age in these studies. Age did not have a significant effect on systemic exposure.

🤰 Pregnancy ~1 min read ▾

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.

🧒 Pediatric Use 16 words ▾

8.4Pediatric Use The safety and effectiveness of BYOOVIZ in pediatric patients have not been established.

🧓 Geriatric Use 68 words ▾

8.5Geriatric Use In the clinical studies, approximately 76% (2449 of 3227) of patients randomized to treatment with ranibizumab were ≥ 65 years of age and approximately 51% (1644 of 3227) were ≥ 75 years of age [ see Clinical Studies (14) ]. No notable differences in efficacy or safety were seen with increasing age in these studies. Age did not have a significant effect on systemic exposure.

🆘 Overdosage 26 words ▾

10 OVERDOSAGE More concentrated doses as high as 2 mg ranibizumab in 0.05 mL have been administered to patients. No additional unexpected adverse reactions were seen.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Ranibizumab products bind to the receptor binding site of active forms of VEGF-A, including the biologically active, cleaved form of this molecule, VEGF 110 . VEGF-A has been shown to cause neovascularization and leakage in models of ocular angiogenesis and vascular occlusion and is thought to contribute to pathophysiology of neovascular AMD, mCNV, and macular edema following RVO. The binding of ranibizumab products to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.

12.2Pharmacodynamics Increased retinal thickness (i.e., center point thickness (CPT) or central foveal thickness (CFT)), as assessed by optical coherence tomography (OCT) is associated with neovascular AMD, mCNV, and macular edema following RVO. Leakage from choroidal neovascularization (CNV) as assessed by fluorescein angiography (FA) is associated with neovascular AMD and mCNV. Neovascular (Wet) Age-Related Macular Degeneration In Study AMD-3, CPT was assessed by time domain (TD)-OCT in 118 of 184 patients.

TD-OCT measurements were collected at baseline, Months 1, 2, 3, 5, 8, and 12. In patients treated with ranibizumab, CPT decreased, on average, more than in the sham group from baseline through Month 12. CPT decreased by Month 1 and decreased further at Month 3, on average.

In this study, CPT data did not provide information useful in influencing treatment decisions [ see Clinical Studies (14.1) ]. In Study AMD-4, CFT was assessed by spectral domain (SD)-OCT in all patients; on average, CFT reductions were observed beginning at Day 7 following the first ranibizumab injection through Month 24. CFT data did not provide information capable of predicting final visual acuity results [ see Clinical Studies (14.1) ].

In patients treated with ranibizumab, the area of CNV leakage, on average, decreased by Month 3 as assessed by FA. The area of CNV leakage for an individual patient was not correlated with visual acuity. Macular Edema Following Retinal Vein Occlusion On average, CPT reductions were observed in Studies RVO-1 and RVO-2 beginning at Day 7 following the first ranibizumab injection through Month 6.

CPT was not evaluated as a means to guide treatment decisions [ see Clinical Studies (14.2) ]. Myopic Choroidal Neovascularization On average CFT reductions were observed as early as Month 1, and were greater in the ranibizumab groups compared to PDT [ see Clinical Studies (14.3) ].

12.3Pharmacokinetics In patients with neovascular AMD, following monthly intravitreal administration of 0.5 mg ranibizumab, mean (±SD) maximum ranibizumab serum concentrations were 1.7 (± 1.1) ng/mL. These concentrations were below the concentration range of ranibizumab (11 to 27 ng/mL) that was necessary to inhibit the biological activity of VEGF-A by 50%, as measured in an in vitro cellular proliferation assay (based on human umbilical vein endothelial cells (HUVEC)). No significant change from baseline was observed in the mean plasma VEGF concentrations following three monthly 0.5 mg intravitreal injections.

The maximum observed serum concentration was dose proportional over the dose range of 0.05 to 2 mg/eye. Serum ranibizumab concentrations in RVO patients were similar to those observed in neovascular AMD patients. Based on a population pharmacokinetic analysis of patients with neovascular AMD, maximum serum concentrations are predicted to be reached at approximately 1 day after monthly intravitreal administration of ranibizumab 0.5 mg/eye.

Based on the disappearance of ranibizumab from serum, the estimated average vitreous elimination half-life was approximately 9 days. Steady-state minimum concentration is predicted to be 0.22 ng/mL with a monthly dosing regimen. In humans, serum ranibizumab concentrations are predicted to be approximately 90,000-fold lower than vitreal c… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 97 words ▾

12.1Mechanism of Action Ranibizumab products bind to the receptor binding site of active forms of VEGF-A, including the biologically active, cleaved form of this molecule, VEGF 110 . VEGF-A has been shown to cause neovascularization and leakage in models of ocular angiogenesis and vascular occlusion and is thought to contribute to pathophysiology of neovascular AMD, mCNV, and macular edema following RVO. The binding of ranibizumab products to VEGF-A prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.

📦 How Supplied / Storage and Handling 105 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Each BYOOVIZ 0.5 mg carton (NDC 64406-019-01) contains a single-dose, 2-mL glass vial designed to deliver 0.05 mL of 10 mg/mL ranibizumab-nuna solution that is clear to slightly opalescent and colorless to pale yellow. EACH CARTON IS FOR SINGLE-EYE USE ONLY. BYOOVIZ should be refrigerated at 2°C to 8°C (36°F to 46°F).

DO NOT FREEZE. Do not use beyond the date stamped on the label. Protect BYOOVIZ vials from light and store in the original carton until time of use.

Prior to use, the unopened vial can be stored at temperatures up to 86°F (30°C) for up to 72 hours.

📦 Storage and Handling 59 words ▾

BYOOVIZ should be refrigerated at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE. Do not use beyond the date stamped on the label. Protect BYOOVIZ vials from light and store in the original carton until time of use. Prior to use, the unopened vial can be stored at temperatures up to 86°F (30°C) for up to 72 hours.

📋 Description 137 words ▾

11 DESCRIPTION BYOOVIZ (ranibizumab-nuna) is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment designed for intraocular use. Ranibizumab-nuna binds to and inhibits the biologic activity of human vascular endothelial growth factor A (VEGF-A). Ranibizumab-nuna, which lacks an Fc region, has a molecular weight of approximately 48 kilodaltons and is produced by an E. coli expression system in a nutrient medium containing the antibiotic tetracycline.

Tetracycline is not detectable in the final product. BYOOVIZ (ranibizumab-nuna) injection is a sterile, clear to slightly opalescent and colorless to pale yellow solution in a single-dose glass vial for intravitreal use. BYOOVIZ is supplied as a preservative-free, sterile solution in a single-dose container designed to deliver 0.05 mL of 10 mg/mL BYOOVIZ (0.5 mg dose vial) aqueous solution with 10 mM histidine HCl, 10% α,α-trehalose dihydrate, 0.01% polysorbate 20, pH 5.5.

💬 Information for Patients 61 words ▾

17 PATIENT COUNSELING INFORMATION Advise patients that in the days following BYOOVIZ administration, patients are at risk of developing endophthalmitis and retinal vasculitis with or without occlusion. 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 , 5.4) ].

🧬 Pharmacokinetics ~1 min read ▾

12.3Pharmacokinetics In patients with neovascular AMD, following monthly intravitreal administration of 0.5 mg ranibizumab, mean (±SD) maximum ranibizumab serum concentrations were 1.7 (± 1.1) ng/mL. These concentrations were below the concentration range of ranibizumab (11 to 27 ng/mL) that was necessary to inhibit the biological activity of VEGF-A by 50%, as measured in an in vitro cellular proliferation assay (based on human umbilical vein endothelial cells (HUVEC)). No significant change from baseline was observed in the mean plasma VEGF concentrations following three monthly 0.5 mg intravitreal injections.

The maximum observed serum concentration was dose proportional over the dose range of 0.05 to 2 mg/eye. Serum ranibizumab concentrations in RVO patients were similar to those observed in neovascular AMD patients. Based on a population pharmacokinetic analysis of patients with neovascular AMD, maximum serum concentrations are predicted to be reached at approximately 1 day after monthly intravitreal administration of ranibizumab 0.5 mg/eye.

Based on the disappearance of ranibizumab from serum, the estimated average vitreous elimination half-life was approximately 9 days. Steady-state minimum concentration is predicted to be 0.22 ng/mL with a monthly dosing regimen. In humans, serum ranibizumab concentrations are predicted to be approximately 90,000-fold lower than vitreal concentrations.

In pharmacokinetic covariate analyses, 48% (520/1091) of patients had renal impairment (35% mild, 11% moderate, and 2% severe). Because the increases in plasma ranibizumab exposures in these patients are not considered clinically significant, no dosage adjustment is needed based on renal impairment status.

🧬 Pharmacodynamics ~1 min read ▾

12.2Pharmacodynamics Increased retinal thickness (i.e., center point thickness (CPT) or central foveal thickness (CFT)), as assessed by optical coherence tomography (OCT) is associated with neovascular AMD, mCNV, and macular edema following RVO. Leakage from choroidal neovascularization (CNV) as assessed by fluorescein angiography (FA) is associated with neovascular AMD and mCNV. Neovascular (Wet) Age-Related Macular Degeneration In Study AMD-3, CPT was assessed by time domain (TD)-OCT in 118 of 184 patients.

TD-OCT measurements were collected at baseline, Months 1, 2, 3, 5, 8, and 12. In patients treated with ranibizumab, CPT decreased, on average, more than in the sham group from baseline through Month 12. CPT decreased by Month 1 and decreased further at Month 3, on average.

In this study, CPT data did not provide information useful in influencing treatment decisions [ see Clinical Studies (14.1) ]. In Study AMD-4, CFT was assessed by spectral domain (SD)-OCT in all patients; on average, CFT reductions were observed beginning at Day 7 following the first ranibizumab injection through Month 24. CFT data did not provide information capable of predicting final visual acuity results [ see Clinical Studies (14.1) ].

In patients treated with ranibizumab, the area of CNV leakage, on average, decreased by Month 3 as assessed by FA. The area of CNV leakage for an individual patient was not correlated with visual acuity. Macular Edema Following Retinal Vein Occlusion On average, CPT reductions were observed in Studies RVO-1 and RVO-2 beginning at Day 7 following the first ranibizumab injection through Month 6.

CPT was not evaluated as a means to guide treatment decisions [ see Clinical Studies (14.2) ]. Myopic Choroidal Neovascularization On average CFT reductions were observed as early as Month 1, and were greater in the ranibizumab groups compared to PDT [ see Clinical Studies (14.3) ].

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES Unless otherwise noted, visual acuity was measured at a distance of 4 meters.

14.1Neovascular (Wet) Age-Related Macular Degeneration (AMD) The safety and efficacy of ranibizumab were assessed in three randomized, double-masked, sham- or active-controlled studies in patients with neovascular AMD. A total of 1323 patients (ranibizumab 879, control 444) were enrolled in the three studies. Studies AMD-1 and AMD-2 In Study AMD-1, patients with minimally classic or occult (without classic) CNV lesions received monthly ranibizumab 0.3 mg or 0.5 mg intravitreal injections or monthly sham injections.

Data are available through Month 24. Patients treated with ranibizumab in Study AMD-1 received a mean of 22 total treatments out of a possible 24 from Day 0 to Month 24. In Study AMD-2, patients with predominantly classic CNV lesions received one of the following: 1) monthly ranibizumab 0.3 mg intravitreal injections and sham PDT; 2) monthly ranibizumab 0.5 mg intravitreal injections and sham PDT; or 3) sham intravitreal injections and active PDT.

Sham PDT (or active PDT) was given with the initial ranibizumab (or sham) intravitreal injection and every 3 months thereafter if FA showed persistence or recurrence of leakage. Data are available through Month 24. Patients treated with ranibizumab in Study AMD-2 received a mean of 21 total treatments out of a possible 24 from Day 0 through Month 24.

In both studies, the primary efficacy endpoint was the proportion of patients who maintained vision, defined as losing fewer than 15 letters of visual acuity at 12 months compared with baseline. Almost all ranibizumab--treated patients (approximately 95%) maintained their visual acuity. Among ranibizumab--treated patients, 31% to 37% experienced a clinically significant improvement in vision, defined as gaining 15 or more letters at 12 months.

The size of the lesion did not significantly affect the results. Detailed results are shown in Table 3, Table 4, and Figure 1 below. Table 3 Visual Acuity Outcomes at Month 12 and Month 24 in Study AMD-1 Outcome Measure Month Sham n=229 Ranibizumab 0.5 mg n=230 Estimated Difference (95% CI) Adjusted estimate based on the stratified model; p <

0.01Loss of <15 letters in visual acuity (%) 12 60% 91% 30% (23%, 37%) 24 56% 89% 33% (26%, 41%) Gain of ≥15 letters in visual acuity (%) 12 6% 31% 25% (18%, 31%) 24 4% 30% 25% (18%, 31%) Mean change in visual acuity (letters) (SD) 12 -11.0 (17.9) +6.3 (14.1) 17.1 (14.2, 20.0) 24 -15.0 (19.7) +5.5 (15.9) 20.1 (16.9, 23.4) Table 4 Visual Acuity Outcomes at Month 12 and Month 24 in Study AMD-2 Outcome Measure Month PDT n=141 Ranibizumab 0.5 mg n=139 Estimated Difference (95% CI) Adjusted estimate based on the stratified model; p <

0.01Loss of <15 letters in visual acuity (%) 12 66% 98% 32% (24%, 40%) 24 65% 93% 28% (19%, 37%) Gain of ≥15 letters in visual acuity (%) 12 11% 37% 26% (17%, 36%) 24 9% 37% 29% (20%, 39%) Mean change in visual acuity (letters) (SD) 12 -8.5 (17.8) +11.0 (15.8) 19.8 (15.9, 23.7) 24 -9.1 (18.7) +10.9 (17.3) 20 (16.0, 24.4) Figure 1 Mean Change in Visual Acuity Visual acuity was measured at a distance of 2 meters from Baseline to Month 24 in Study AMD-1 and Study AMD-2 AMD-1 AMD-2 Ranibizumab 0.5 mg (n=240) Ranibizumab 0.5 mg (n=139) Sham (n=238) Verteporfin PDT (n=143) Patients in the group treated with ranibizumab had minimal observable CNV lesion growth, on average.

At Month 12, the mean change in the total area of the CNV lesion was 0.1-0.3 disc areas (DA) for ranibizumab versus 2.3-2.6 DA for the control arms. At Month 24, the mean change in the total area of the CNV lesion was 0.3-0.4 DA for ranibizumab versus 2.9-3.1 DA for the control arms. Figure 1 Figure Figure Figure Figure Study AMD-3 Study AMD-3 was a randomized, double-masked, sham-controlled, 2-year study designed to assess the safety and efficacy of ranibizumab in patients with neovascular AMD (with or without a classic CNV component).

Data are available through… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 54 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Animal studies have not been conducted to determine the carcinogenic potential of ranibizumab products. Based on the anti-VEGF mechanism of action of ranibizumab products, treatment with ranibizumab products may pose a risk to reproductive capacity [ see Females and Males of Reproductive Potential (8.3) ].

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 51 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Animal studies have not been conducted to determine the carcinogenic potential of ranibizumab products. Based on the anti-VEGF mechanism of action of ranibizumab products, treatment with ranibizumab products may pose a risk to reproductive capacity [ see Females and Males of Reproductive Potential (8.3) ].

📄 Recent Major Changes 13 words ▾

Warnings and Precautions, Retinal Vasculitis with or without Occlusion ( 5.4 ) 8/2025

📄 Package Label / Principal Display Panel 90 words ▾

PRINCIPAL DISPLAY PANEL - 0.5 mg Vial Carton NDC 64406-019-01 Rx only Byooviz™ 0.5mg wAMD RVO mCNO (ranibizumab-nuna) Injection 0.5 mg single-dose vial. Discard unused portion. IMPORTANT: A 5-micron sterile filter needle (19-gauge x 1-1/2 inch) is required for preparation, but not included.

See enclosed package insert. For intravitreal injection. INDICATED FOR: Neovascular (wet) age-related macular degeneration (AMD) Macular edema following retinal vein occlusion (RVO) Myopic choroidal neovascularization (mCNV) KEEP REFRIGERATED.

DO NOT FREEZE. PROTECT VIAL FROM LIGHT. SAMSUNG BIOEPIS, Biogen ® PRINCIPAL DISPLAY PANEL - 0.5 mg Vial Carton

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
419
Units reimbursed last 4 qtrs
23
Gross reimbursed last 4 qtrs
$228.5K
Avg / prescription
$545.31
Avg / unit
$9,886.89
Latest quarter Q1 2026
19Rx
Fee-for-service vs managed care ⓘ
71% FFS 29% MCO
Fee-for-service · 296 Rx Managed care · 123 Rx
State Medicaid map
Alaska: no data reported AK Maine: 8 units · 0.6 per 100k residents ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 1 units · 0.0 per 100k residents MN Wisconsin: no data reported WI Michigan: no data reported MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 3 units · 0.1 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: 9 units · 0.1 per 100k residents MA California: no data reported CA Utah: no data reported UT Colorado: 1 units · 0.0 per 100k residents CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: 1 units · 0.0 per 100k residents VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
0.00.6
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Maine 0.6 /100k
2 Massachusetts 0.1 /100k
3 Oregon 0.1 /100k
4 Minnesota 0.0 /100k
5 Colorado 0.0 /100k
6 Virginia 0.0 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
1 vial this page64406-0019-01 419 Rx · $228,486
1 vial64406-0019-08 No Medicaid data
Drug total (last 4 qtrs): 419 Rx · 23 units · $228,486 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk ✓ Available
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page it is currently marketed — but BIOGEN INC. has reported a marketing end date of 2028-07-19, after which this package is expected to stop being marketed. The directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 1 vial (64406-0019-08). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
BIOGEN INC. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code Q5124 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 64406-0017-01 · Biogen 64406-0020-01 · Biogen →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.