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CRYSVITA Burosumab 20 mg/mL Injection, 1 mL — NDC 42747-0203-01 package photo
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CRYSVITA Burosumab 20 mg/mL Injection, 1 mL — NDC 42747-203-01 (Billing 42747-0203-01)

by Kyowa Kirin, Inc. · 1 mL in 1 VIAL, SINGLE-USE

This is a package of 1 mL of CRYSVITA Burosumab 20 mg/mL Injection from Kyowa Kirin, Inc., marketed since Apr 2018 and currently FDA-listed. It is this product's only package size.

NDC 42747-0203-01
🏷️ FDA NDC (as labeled) 42747-203-01 billing pads the product segment with a zero
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 42747-203-01 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
42747 labeler · 203 product · 01 package
Package marketed since
Sep 1, 2023
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Billing quantity
1 mL per package
Barcode (UPC-A, from the NDC)
3 4274720301 7
Medicaid fills, this package
2,686 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) 42747-203-01
Product NDC 42747-203
11-digit billing NDC 42747020301
NCPDP billing unit ML — per mL (volume)
RxCUI 2043859, 2043864, 2043868, 2043870, 2043876, 2043878
UNII G9WJT6RD29
Application # BLA761068
SPL Set ID 102f96a0-6e3a-4fc1-b204-34d604683af6
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2018-04-18
Route SUBCUTANEOUS
Dosage form INJECTION
Substance BUROSUMAB
Biologic (Purple Book) 351(a)

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

GPI-14 30909510602020
GCN Seq No 078330
GCN 44642
HICL code 044867
Ingredient (HICL) Burosumab-Twza
HIC1 code C
Therapeutic class — broad (HIC1) Electrolyte Balance/Metabolism/Nutrition
HIC2 code C7
Therapeutic class — intermediate (HIC2) Metabolic Inhibitors And Stimulants
HIC3 code C7J
Therapeutic class — specific (HIC3) Fibroblast Growth Factor 23 (Fgf23) Inhibitors,Mab
AHFS code 40:92.00.00
AHFS class Electrolytic,Caloric,Water Balance Misc,
FDB label name CRYSVITA 20 MG/ML VIAL
FDB brand name Crysvita
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 078330
  • GCN: 44642
  • GPI-14 (Medi-Span): 30909510602020
  • HICL (First Databank): 044867
  • AHFS class code: 40:92.00.00
  • RxCUI (RxNorm): 2043859
Why two NDCs? The FDA registers this code as 42747-203-01 — 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 → 42747-0203-01. 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 Other drugs affecting bone structure and mineralization class.

Drug family (ATC) Other drugs affecting bone structure and mineralization
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 CRYSVITA 20 MG/ML VIAL Ingredient Burosumab-Twza

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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $9,639.65 $9,639.65 / 1 vial
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J0584 $513.371 / J0584 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)42747-203-01
11-digit billing NDC42747-0203-01
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ0584
DescriptorINJECTION, BUROSUMAB-TWZA 1 MG
Billing units / pkg20 units
How the units are derivedThis package is 1 ML; the HCPCS unit is 1 MG, so one package = 20 billing units.
Medicare Part B spend (2026 (Q1))$6,303,329 · 203 claims · $31,050.88 per claim (all NDCs under J0584)
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
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
42747-0203-01 You're viewing this Main listing 1 mL in 1 VIAL, SINGLE-USE 2023-09-01 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Crysvita 20 mg/mLthis 42747-0203-01 Kyowa 1 ml — — 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

🏛️
2018
First FDA approval
Apr 2018
📍
2026
Currently FDA-listed
8 years listed
🛡️
2030
Latest patent/protection listed
not a guaranteed launch date
🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Apr 2030. This may affect when biosimilars become widely available, but it is not a guaranteed launch date.
📅 FDA approved Apr 17, 2018 ⏳ ~3.5 yr to latest listed protection

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
Crysvitaburosumab-twza
🔒 No FDA-licensed biosimilars or interchangeable biosimilars are listed yet for this biologic. It currently has no biosimilar competition in the FDA Purple Book.
Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.
Patents & exclusivity — FDA Purple Book
Exclusivity RefProduct
2018 2020 2022 2024 2026 2028 2030
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 dateApr 17, 2030
Common questions
Is there a biosimilar for CRYSVITA 20 MG/ML VIAL?
No FDA-licensed biosimilar is currently listed for this biologic in the FDA Purple Book.
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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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

LabelerKyowa Kirin, Inc.
FDA applicationBLA761068 (BLA)
Labeler code42747
First marketedApr 2018
Product typeHuman Prescription Drug
Portfolio7 products on file

More NDCs from Kyowa Kirin, Inc. labeler code 42747

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 134 words ▾

1 INDICATIONS AND USAGE CRYSVITA is a fibroblast growth factor 23 (FGF23) blocking antibody indicated for: The treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older. ( 1.1 ) The treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older. ( 1.2 )

1.1X-linked Hypophosphatemia CRYSVITA is indicated for the treatment of X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older.

1.2Tumor-induced Osteomalacia CRYSVITA is indicated for the treatment of FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION For subcutaneous use only ( 2 ) Prior to starting CRYSVITA, discontinue oral phosphate and/or active vitamin D analogs for one week ( 2.1 ) Pediatric XLH (6 months and older): For patients who weigh less than 10 kg, starting dose regimen is 1 mg/kg of body weight rounded to the nearest 1 mg, administered every two weeks ( 2.2 ) For patients who weigh 10 kg and greater, starting dose regimen is 0.8 mg/kg of body weight rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.

( 2.2 ) Dose may be increased up to approximately 2 mg/kg (maximum 90 mg), administered every two weeks to achieve normal serum phosphorus. ( 2.2 ) Adult XLH: Starting dose is 1 mg/kg body weight rounded to the nearest 10 mg up to a maximum dose of 90 mg administered every four weeks. Dose may be increased up to 1 mg/kg rounded to the nearest 10 mg up to a maximum dose of 90 mg administered every two weeks.

( 2.3 ) Pediatric TIO (2 years and older): Starting dose is 0.4 mg/kg of body weight rounded to the nearest 10 mg every 2 weeks. Dose may be increased up to 2 mg/kg not to exceed 180 mg, administered every two weeks. ( 2.4 ) Adult TIO: Starting dose is 0.5 mg/kg every four weeks.

Dose may be increased up to 2 mg/kg not to exceed 180 mg, administered every two weeks. ( 2.5 )

2.1Important Information Prior to Initiation of CRYSVITA Prior to starting CRYSVITA, discontinue oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) for one week [see Contraindications (4) , Warnings and Precautions (5.3) ] . Prior to starting CRYSVITA, fasting serum phosphorus concentration should be below the reference range for age [see Contraindications (4) ]. In patients at high risk for hypercalcemia (e.g., pre-existing hyperparathyroidism, prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment) assess serum calcium and parathyroid hormone levels prior to starting CRYSVITA [see Warnings and Precautions (5.3) ] .

CRYSVITA is administered by subcutaneous injection and should be administered by a healthcare provider. The maximum volume of CRYSVITA per injection is 1.5 mL. If multiple injections are required, administer at different injection sites.

2.2Recommended Dosage for Pediatric Patients with X-linked Hypophosphatemia (6 months to less than 18 years of age) For patients who weigh less than 10 kg, the recommended starting dosage is 1 mg/kg of body weight, rounded to the nearest 1 mg, administered every two weeks. For patients who weigh 10 kg and greater, the recommended starting dose regimen is 0.8 mg/kg of body weight, rounded to the nearest 10 mg, administered every two weeks. The minimum starting dose is 10 mg up to a maximum dose of 90 mg.

After initiation of treatment with CRYSVITA, measure fasting serum phosphorus every 4 weeks for the first 3 months of treatment, and thereafter as appropriate. If serum phosphorus is above the lower limit of the reference range for age and below 5 mg/dL, continue treatment with the same dose. Follow dose adjustment schedule below to maintain serum phosphorus within the reference range for age.

Dose Adjustment Reassess fasting serum phosphorus level 4 weeks after dose adjustment. Do not adjust CRYSVITA more frequently than every 4 weeks. Dose Increase : For patients who weigh less than 10 kg, if serum phosphorus is below the reference range for age, the dose may be increased to 1.5 mg/kg, rounded to the nearest 1 mg, administered every two weeks.

If additional dose increases are needed, the dose may be increased to the maximum dose of 2 mg/kg, rounded to the nearest 1 mg, administered every two weeks. For patients who weigh 10 kg or greater, if serum phosphorus is below the reference range for age, the dose may be increased stepwise up to approximately 2 mg/kg, administered every two weeks (maximum dose of 90 mg) according to the dosing schedule shown in Table 1.… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 42 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 10 mg/mL, 20 mg/mL, or 30 mg/mL clear to slightly opalescent and colorless to pale brown-yellow solution in a single-dose vial. Injection: 10 mg/mL, 20 mg/mL, or 30 mg/mL in a single-dose vial ( 3 )

⛔ Contraindications 125 words ▾

4 CONTRAINDICATIONS CRYSVITA is contraindicated: In concomitant use with oral phosphate and/or active vitamin D analogs (e.g. calcitriol, paricalcitol, doxercalciferol, calcifediol) due to the risk of hyperphosphatemia [see Warnings and Precautions (5.2) and Drug Interactions (7.1) ] . When serum phosphorus is within or above the normal range for age [see Warnings and Precautions (5.2) ] . In patients with severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism [see Use In Specific Population (8.6) ] .

With oral phosphate and/or active vitamin D analogs. ( 4 ) When serum phosphorus is within or above the normal range for age. ( 4 ) In patients with severe renal impairment or end stage renal disease.

( 4 )

⚠️ Warnings and Cautions ~1 min read ▾

5 WARNINGS AND PRECAUTIONS Hypersensitivity : Discontinue CRYSVITA if serious hypersensitivity reactions occur and initiate appropriate medical treatment. ( 5.1 ) Hyperphosphatemia and Risk of Nephrocalcinosis : For patients already taking CRYSVITA, dose interruption and/or dose reduction may be required based on a patient's serum phosphorus levels. ( 5.2 , 6.1 ) Hypercalcemia : Increases in serum calcium have been reported.

Monitor serum calcium and parathyroid hormone levels in patients at high risk for hypercalcemia before and during treatment. ( 5.3 ) Injection Site Reactions : Administration of CRYSVITA may result in local injection site reactions. Discontinue CRYSVITA if severe injection site reactions occur and administer appropriate medical treatment.

( 5.4 , 6.1 )

5.1Hypersensitivity Hypersensitivity reactions (e.g. rash, urticaria) have been reported in patients with CRYSVITA. Discontinue CRYSVITA if serious hypersensitivity reactions occur and initiate appropriate medical treatment [see Adverse Reactions (6.1) ] .

5.2Hyperphosphatemia and Risk of Nephrocalcinosis Increases in serum phosphorus to above the upper limit of normal may be associated with an increased risk of nephrocalcinosis. For patients already taking CRYSVITA, dose interruption and/or dose reduction may be required based on a patient's serum phosphorus levels. Patients with tumor-induced osteomalacia who undergo treatment of the underlying tumor should have dosing interrupted and adjusted to prevent hyperphosphatemia [see Dosage and Administration (2) and Adverse Reactions (6.1) ] .

5.3Hypercalcemia Increases in serum calcium have been reported in patients treated with CRYSVITA. Patients with risk factors such as, pre-existing hyperparathyroidism, prolonged immobilization, dehydration, hypervitaminosis D, or renal impairment, are at higher risk of hypercalcemia. Monitor these patients for serum calcium and parathyroid hormone levels before and during CRYSVITA treatment for moderate to severe hypercalcemia.

In patients with moderate to severe hypercalcemia, CRYSVITA should not be administered until hypercalcemia is adequately managed.

5.4Injection Site Reactions Administration of CRYSVITA may result in local injection site reactions. Discontinue CRYSVITA if severe injection site reactions occur and administer appropriate medical treatment [see Adverse Reactions (6.1) ] .

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are described below and elsewhere in the labeling: Hypersensitivity [see Warnings and Precautions (5.1) ] Hyperphosphatemia and Risk of Nephrocalcinosis [see Warnings and Precautions (5.2) ] Hypercalcemia [see Warnings and Precautions (5.3) Injection Site Reactions [see Warnings and Precautions (5.4) ] Most common adverse reactions (≥25% in the CRYSVITA group and > Active Control) in pediatric XLH patients are: pyrexia, injection site reaction, cough, vomiting, pain in extremity, headache, tooth abscess, dental caries.

( 6.1 ) Most common adverse reactions (>5% and in at least 2 patients more than placebo) in adult XLH patients are: back pain, headache, tooth infection, restless legs syndrome, vitamin D decreased, dizziness, constipation, muscle spasms, blood phosphorus increased. ( 6.1 ) Most common adverse reactions (>10%) in TIO patients are: tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Kyowa Kirin, Inc. at 1-844-768-3544 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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 another drug and may not reflect the rates observed in practice. Adverse Reactions in Pediatric Patients with XLH CRYSVITA was studied in three pediatric XLH studies. Study 1 is a randomized, open-label phase 3 study in XLH patients ages 1 to 12 years, who were randomized to treatment with CRYSVITA or treatment with active control of oral phosphate and active vitamin D (CRYSVITA N = 29, Active Control N = 32).

Study 2 is an open-label phase 2 study in XLH patients ages 5 to 12 years (N = 52). Study 3 is an open-label phase 2 study in XLH patients ages 1 to less than 5 years (N = 13). Overall, the patient population was 1-12 years (mean age 7.0 years), 49% male, and 88% white.

In Study 1, patients randomized to CRYSVITA received a mean dose of approximately 0.90 mg/kg (range 0.8-1.2 mg/kg) every 2 weeks. All patients in this group and the active control group completed 64 weeks of treatment. Adverse reactions occurring in ≥ 10% of subjects in the CRYSVITA group, with higher frequency than in the subjects in the active control group, through the 64-week treatment period in Study 1 are shown in Table 6 .

Table 6: Adverse Reactions Reported in 10% or More of CRYSVITA-Treated Pediatric Patients and with Higher Frequency Than the Active Control Group in Study 1 Adverse Reaction CRYSVITA (N=29) n (%) Active Control (N=32) n (%) n = number of patients with an event; N = total number of patients who received at least one dose of CRYSVITA or active control Pyrexia 16 (55) 6 (19) Injection site reaction Injection site reaction includes: injection site reaction, injection site erythema, injection site pruritus, injection site swelling, injection site pain, injection site rash, injection site bruising, injection site discoloration, injection site discomfort, injection site hematoma, injection site hemorrhage, injection site induration, injection site macule, and injection site urticaria 15 (52) 0 (0) Cough Cough includes: cough and productive cough 15 (52) 6 (19) Vomiting 12 (41) 8 (25) Pain in extremity 11 (38) 10 (31) Headache 10 (34) 6 (19) Tooth abscess Tooth abscess includes: tooth abscess, tooth infection, toothache 10 (34) 4 (13) Dental caries 9 (31) 2 (6) Diarrhea 7 (24) 2 (6) Vitamin D decreased Vitamin D decreased includes: vitamin D deficiency, blood 25-hydroxycholecalciferol decreased, and vitamin D decreased 7 (24) 1 (3) Constipation 5 (17) 0 (0) Rash Rash includes: rash, rash pruritic, rash maculopapular, rash erythematous, rash generalized and rash pustular 4 (14) 2 (6) Nausea 3 (10) 1 (3) In Study 2, 26 of the patients received CRYSVITA at a mean dose of 1.05 mg/kg (ra… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 57 words ▾

7 DRUG INTERACTIONS

7.1Oral Phosphate and Active Vitamin D Analogs Concomitant use of CRYSVITA with oral phosphate and/or active vitamin D analogs will increase phosphate concentrations greater than expected with CRYSVITA alone. This increase may result in hyperphosphatemia which can induce nephrocalcinosis. Concomitant use of CRYSVITA with oral phosphate and/or active vitamin D analogs is contraindicated.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary There are no available data on CRYSVITA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In utero, burosumab-twza exposure in cynomolgus monkeys did not result in teratogenic effects. Adverse effects such as late fetal loss and preterm birth were observed in pregnant cynomolgus monkeys, however, these effects are unlikely to indicate clinical risk because they occurred at a drug exposure that was 15-fold higher, by AUC, than the human exposure at the maximum recommended human dose (MRHD) of 2 mg/kg every 2 weeks and were accompanied by maternal hyperphosphatemia and placental mineralization ( see Data ).

Serum phosphorus levels should be monitored throughout pregnancy [see Dosage and Administration (2.2) ]. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at 1-844-768-3544.

The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data In a reproductive toxicity study in pregnant cynomolgus monkeys, burosumab-twza was administered intravenously once every two weeks from Day 20 of pregnancy to parturition or cesarean section on Day 133, which includes the period of organogenesis, at doses of 0.2-, 2- and 15-fold human exposure at the adult MRHD of 2 mg/kg every 2 weeks.

The treatment did not result in teratogenic effects in fetuses or offspring. An increase in late fetal loss, a shortened gestation period, and an increased incidence of preterm births were observed at 15-fold human exposure at the adult MRHD of 2 mg/kg every 2 weeks, concomitant with maternal hyperphosphatemia and placental mineralization. Burosumab-twza was detected in serum from fetuses indicating transport across the placenta.

Hyperphosphatemia but no ectopic mineralization was present in fetuses and offspring of dams exposed to 15-fold human exposure at the MRHD of 2 mg/kg dose every 2 weeks. Burosumab-twza did not affect pre- and postnatal growth including survivability of the offspring.

8.2Lactation Risk Summary There is no information regarding the presence of burosumab-twza in human milk, or the effects of burosumab-twza on milk production or the breastfed infant. Maternal IgG is present in breast milk. However, the effects of local gastrointestinal exposure and limited systemic exposure to burosumab-twza in the breastfed infant are unknown.

The lack of clinical data during lactation precludes a clear determination of the risk of CRYSVITA to an infant during lactation. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CRYSVITA and any potential adverse effects on the breastfed infant from CRYSVITA or from the underlying maternal condition.

8.4Pediatric Use Safety and effectiveness of CRYSVITA have been established in pediatric patients 6 months and older. Safety and effectiveness in pediatric patients 1 year and older with XLH are based on one phase 3, open-label, active control study [61 patients 1-12 years of age (Study 1)] and two open-label studies [52 patients 5 to 12 years of age (Study 2), and 13 patients 1 to 4 years of age (Study 3)] evaluating serum phosphorus and radiographic findings. Safety and effectiveness in patients 6 months to 1 year and adolescents are supported by evidence from the studies in pediatric patients 1 year to less than 13 years of age with additional modeling and simulation of adult and pediatric pharmacokinetic (PK) and pharmacodynamic (PD) data to inform dosing [see Adverse Reactions (6.1) and Clinical Studies (14) ] .

Safety and effectiveness for CRYSVITA in pediatric patients with XLH below the age of 6 months have not been established . Safety and effectiveness of CRYSVITA in pediatric patient… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary There are no available data on CRYSVITA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In utero, burosumab-twza exposure in cynomolgus monkeys did not result in teratogenic effects. Adverse effects such as late fetal loss and preterm birth were observed in pregnant cynomolgus monkeys, however, these effects are unlikely to indicate clinical risk because they occurred at a drug exposure that was 15-fold higher, by AUC, than the human exposure at the maximum recommended human dose (MRHD) of 2 mg/kg every 2 weeks and were accompanied by maternal hyperphosphatemia and placental mineralization ( see Data ).

Serum phosphorus levels should be monitored throughout pregnancy [see Dosage and Administration (2.2) ]. Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at 1-844-768-3544.

The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Data Animal Data In a reproductive toxicity study in pregnant cynomolgus monkeys, burosumab-twza was administered intravenously once every two weeks from Day 20 of pregnancy to parturition or cesarean section on Day 133, which includes the period of organogenesis, at doses of 0.2-, 2- and 15-fold human exposure at the adult MRHD of 2 mg/kg every 2 weeks.

The treatment did not result in teratogenic effects in fetuses or offspring. An increase in late fetal loss, a shortened gestation period, and an increased incidence of preterm births were observed at 15-fold human exposure at the adult MRHD of 2 mg/kg every 2 weeks, concomitant with maternal hyperphosphatemia and placental mineralization. Burosumab-twza was detected in serum from fetuses indicating transport across the placenta.

Hyperphosphatemia but no ectopic mineralization was present in fetuses and offspring of dams exposed to 15-fold human exposure at the MRHD of 2 mg/kg dose every 2 weeks. Burosumab-twza did not affect pre- and postnatal growth including survivability of the offspring.

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use Safety and effectiveness of CRYSVITA have been established in pediatric patients 6 months and older. Safety and effectiveness in pediatric patients 1 year and older with XLH are based on one phase 3, open-label, active control study [61 patients 1-12 years of age (Study 1)] and two open-label studies [52 patients 5 to 12 years of age (Study 2), and 13 patients 1 to 4 years of age (Study 3)] evaluating serum phosphorus and radiographic findings. Safety and effectiveness in patients 6 months to 1 year and adolescents are supported by evidence from the studies in pediatric patients 1 year to less than 13 years of age with additional modeling and simulation of adult and pediatric pharmacokinetic (PK) and pharmacodynamic (PD) data to inform dosing [see Adverse Reactions (6.1) and Clinical Studies (14) ] .

Safety and effectiveness for CRYSVITA in pediatric patients with XLH below the age of 6 months have not been established . Safety and effectiveness of CRYSVITA in pediatric patients 2 years and older with TIO are supported by evidence from the studies in adult patients with TIO with additional modeling and simulation of PK data from adult and pediatric XLH patients and adult TIO patients to inform dosing. Safety and effectiveness for CRYSVITA in pediatric patients with TIO below the age of 2 years have not been established.

🧓 Geriatric Use 83 words ▾

8.5Geriatric Use Clinical studies of CRYSVITA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

🆘 Overdosage 166 words ▾

10 OVERDOSAGE There have been no reports of overdose with CRYSVITA. CRYSVITA has been administered in pediatric clinical trials without dose limiting toxicity using doses up to 2 mg/kg body weight with a maximal dose of 90 mg, administered every two weeks. In XLH adult clinical trials, no dose limiting toxicity has been observed using doses up to 1 mg/kg or a maximal total dose of 128 mg every 4 weeks.

In non-XLH rabbits and cynomolgus monkeys, ectopic mineralization in multiple tissues and organs was observed at doses of burosumab-twza that resulted in supra-physiologic serum phosphate levels. Adverse effects on bone including reductions in bone mineral density, bone mineralization and bone strength were also observed at exposure greater than human exposure [ see Nonclinical Toxicology (13.2) ]. In case of overdose, it is recommended that serum phosphorus levels, serum calcium levels and renal function be measured immediately and monitored periodically until resolution to normal/baseline levels.

In case of hyperphosphatemia, withhold CRYSVITA and initiate appropriate medical treatment.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action X-linked hypophosphatemia is caused by excess fibroblast growth factor 23 (FGF23) which suppresses renal tubular phosphate reabsorption and the renal production of 1,25 dihydroxy vitamin D. Burosumab-twza binds to and inhibits the biological activity of FGF23 restoring renal phosphate reabsorption and increasing the serum concentration of 1,25 dihydroxy vitamin D.

12.2Pharmacodynamics Following SC administration in XLH and TIO patients, higher burosumab-twza concentrations were associated with greater increase of serum phosphorus levels. The increase in serum phosphorus was reversible and returned to baseline with elimination of systemic burosumab-twza . Ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) showed dose-dependent increases from baseline [see Clinical Studies (14) ].

Elevation in serum total FGF23 was observed after initiation of burosumab-twza treatment, however, the clinical implication is unknown.

12.3Pharmacokinetics The following pharmacokinetic parameters were observed in patients with XLH administered the approved recommended starting dosage based on a 70 kg patient, unless otherwise specified. Based on the population PK analysis, the PK characteristics of burosumab-twza were similar between patients with XLH and TIO. Burosumab-twza exhibited linear pharmacokinetics following SC injections within the dose range of 0.1 to 1 mg/kg (0.08 to 0.8 times the maximum approved recommended dosage based on a 70 kg patient with XLH).

The steady-state trough mean (± SD) concentration of burosumab-twza was 5.8 (± 3.4) mcg/mL in adult XLH patients. Absorption The burosumab-twza mean T max values ranged from 8 to 11 days. Distribution The apparent volume of distribution of burosumab-twza is 8 L.

Elimination The apparent clearance is 0.290 L/day. The half-life of burosumab-twza is approximately 19 days. Metabolism The exact pathway for burosumab-twza metabolism has not been characterized.

Burosumab-twza is expected to be degraded into small peptides and amino acids via catabolic pathways. Specific Populations No clinical significant difference in burosumab-twza pharmacokinetics was observed based on age. The effect of renal or hepatic impairment on the pharmacokinetics of burosumab-twza is unknown.

Pediatric Patients The steady-state trough concentration was 15.8 (± 9.4) mcg/mL in XLH patients aged 5-12 years, and 11.2 (± 4.6) mcg/mL in XLH patients aged 1-4 years. Body Weight Clearance and volume of distribution of burosumab-twza increases with body weight. Drug Interaction Studies No drug interaction studies have been conducted with CRYSVITA.

12.6Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.

For these reasons, comparison of the incidence of antibodies to CRYSVITA in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. In XLH clinical studies, none (0/13) of the 1- to 4-year-old patients, 19% (10/52) of the 5- to 12-year- old patients, and 15% (20/131) of the adult patients tested positive for anti-drug antibodies (ADA) after receiving CRYSVITA. Among these, three 5- to 12-year-old patients tested positive for neutralizing antibodies.

The presence of ADA was not associated with clinically relevant changes in pharmacokinetics, pharmacodynamics, efficacy, and safety of CRYSVITA in patients with XLH. In one TIO clinical study, 14% (2/14) of the adult patients tested positive for ADA after receiving CRYSVITA. None of the ADA positive patients tested positi… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 54 words ▾

12.1Mechanism of Action X-linked hypophosphatemia is caused by excess fibroblast growth factor 23 (FGF23) which suppresses renal tubular phosphate reabsorption and the renal production of 1,25 dihydroxy vitamin D. Burosumab-twza binds to and inhibits the biological activity of FGF23 restoring renal phosphate reabsorption and increasing the serum concentration of 1,25 dihydroxy vitamin D.

📦 How Supplied / Storage and Handling 119 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING CRYSVITA (burosumab-twza) injection for subcutaneous administration is supplied as a sterile, preservative-free, clear to slightly opalescent and colorless to pale brown-yellow solution. The product is available as one single-dose vial per carton in the following strengths: 10 mg/mL (NDC# 42747-102-01) 20 mg/mL (NDC# 42747-203-01) 30 mg/mL (NDC# 42747-304-01) CRYSVITA vials must be stored in the original carton until the time of use under refrigerated conditions at 36°F to 46°F (2°C to 8°C).

Keep CRYSVITA vial in the original carton to protect from light until time of use. Do not freeze or shake CRYSVITA. Do not use CRYSVITA beyond the expiration date stamped on the carton.

CRYSVITA vials are single-dose only. Discard any unused product.

📦 Storage and Handling 66 words ▾

CRYSVITA vials must be stored in the original carton until the time of use under refrigerated conditions at 36°F to 46°F (2°C to 8°C). Keep CRYSVITA vial in the original carton to protect from light until time of use. Do not freeze or shake CRYSVITA. Do not use CRYSVITA beyond the expiration date stamped on the carton. CRYSVITA vials are single-dose only. Discard any unused product.

📋 Description 138 words ▾

11 DESCRIPTION Burosumab-twza is a human immunoglobulin G subclass 1 (IgG1), anti-human fibroblast growth factor 23 (FGF23) antibody produced by recombinant DNA technology using Chinese hamster ovary cells. Burosumab-twza is composed of two heavy chain (γ1-chain) molecules and two light chain (κ-chain) molecules. Each heavy chain has an N-linked carbohydrate moiety at asparagine 297 (Asn297).

The molecular weight of burosumab-twza determined by mass spectrometry is approximately 147,000. CRYSVITA (burosumab-twza) injection for subcutaneous administration is supplied as a sterile, preservative-free, clear to slightly opalescent and colorless to pale brown-yellow solution in a single-dose vial. Each 1 mL of solution contains 10 mg, 20 mg or 30 mg of burosumab-twza, L-histidine (1.55 mg), L-methionine (1.49 mg), polysorbate 80 (0.5 mg), D-sorbitol (45.91 mg) in Water for Injection, USP.

Hydrochloric acid may be used to adjust to a pH of 6.25.

💬 Information for Patients 172 words ▾

17 PATIENT COUNSELING INFORMATION Drug Interactions Advise patients not to use any oral phosphate and/or active vitamin D analog products [see Contraindications (4) ]. Hypersensitivity Reactions Advise patients that CRYSVITA may cause hypersensitivity events such as rash, injection site rash and urticaria. Instruct the patients to contact their physician if such reactions occur [ see Adverse Reactions (6.1) ].

Injection Site Reactions Inform patients that injection site reactions (e.g. erythema, rash, swelling, bruising, pain, pruritus, urticaria, and hematoma) have occurred at the site of CRYSVITA injection. Instruct the patients to contact their physician if such reactions occur [ see Adverse Reactions (6.1) ]. Restless Legs Syndrome Advise patients that CRYSVITA can induce RLS or worsen the symptoms of existing RLS.

Instruct the patients to contact their physician if such a reaction occurs [ see Adverse Reactions (6.1) ] . Pregnancy Report pregnancies to the Kyowa Kirin, Inc. Adverse Event reporting line at 1-844-768-3544 [see Use in Specific Populations (8.1) ].

Manufactured by: Kyowa Kirin, Inc. Princeton, NJ 08540 U.S. License No.

2077

🧬 Pharmacokinetics ~1 min read ▾

12.3Pharmacokinetics The following pharmacokinetic parameters were observed in patients with XLH administered the approved recommended starting dosage based on a 70 kg patient, unless otherwise specified. Based on the population PK analysis, the PK characteristics of burosumab-twza were similar between patients with XLH and TIO. Burosumab-twza exhibited linear pharmacokinetics following SC injections within the dose range of 0.1 to 1 mg/kg (0.08 to 0.8 times the maximum approved recommended dosage based on a 70 kg patient with XLH).

The steady-state trough mean (± SD) concentration of burosumab-twza was 5.8 (± 3.4) mcg/mL in adult XLH patients. Absorption The burosumab-twza mean T max values ranged from 8 to 11 days. Distribution The apparent volume of distribution of burosumab-twza is 8 L.

Elimination The apparent clearance is 0.290 L/day. The half-life of burosumab-twza is approximately 19 days. Metabolism The exact pathway for burosumab-twza metabolism has not been characterized.

Burosumab-twza is expected to be degraded into small peptides and amino acids via catabolic pathways. Specific Populations No clinical significant difference in burosumab-twza pharmacokinetics was observed based on age. The effect of renal or hepatic impairment on the pharmacokinetics of burosumab-twza is unknown.

Pediatric Patients The steady-state trough concentration was 15.8 (± 9.4) mcg/mL in XLH patients aged 5-12 years, and 11.2 (± 4.6) mcg/mL in XLH patients aged 1-4 years. Body Weight Clearance and volume of distribution of burosumab-twza increases with body weight. Drug Interaction Studies No drug interaction studies have been conducted with CRYSVITA.

🧬 Pharmacodynamics 81 words ▾

12.2Pharmacodynamics Following SC administration in XLH and TIO patients, higher burosumab-twza concentrations were associated with greater increase of serum phosphorus levels. The increase in serum phosphorus was reversible and returned to baseline with elimination of systemic burosumab-twza . Ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) showed dose-dependent increases from baseline [see Clinical Studies (14) ].

Elevation in serum total FGF23 was observed after initiation of burosumab-twza treatment, however, the clinical implication is unknown.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Pediatric X-linked Hypophosphatemia CRYSVITA has been evaluated in three studies enrolling a total of 126 pediatric patients with XLH. Study 1 (NCT 02915705) is a 64-week randomized, open-label study in 61 pediatric XLH patients, 1 to 12 years old that compared treatment with CRYSVITA to active control (oral phosphate and active vitamin D). At time of first dose the mean age of patients was 6.3 years and 44% were male.

All patients had radiographic evidence of rickets at baseline, with an RSS score of ≥ 2.0 and had received oral phosphate and active vitamin D analogs for a mean (SD) duration of 4 (3.1) years. Oral phosphate and active vitamin D analogs were discontinued prior to study enrollment for a 7-day washout period and then reinitiated for patients in the active control group. Patients were randomized to receive either CRYSVITA at a starting dose of 0.8 mg/kg every two weeks or oral phosphate (recommended dose 20-60 mg/kg/day) and active vitamin D (recommended doses calcitriol 20-30 ng/kg/day or alfacalcidol 40-60 ng/kg/day).

Patients randomized to active control received a mean oral phosphate dose of approximately 41 mg/kg/day (range 18 to 110 mg/kg/day) at Week 40 and approximately 46 mg/kg/day (range 18 mg/kg/day to 166 mg/kg/day) at Week 64. They also received either a mean oral calcitriol dose of 26 ng/kg/day at Week 40 and 27 ng/kg/day at Week 64 or a therapeutically equivalent amount of alfacalcidol. Eight patients in the CRYSVITA arm titrated up to 1.2 mg/kg based on serum phosphorus measurements.

All patients completed at least 64 weeks on study. Serum Phosphorus In Study 1, CRYSVITA increased mean (SD) serum phosphorus levels from 2.4 (0.24) mg/dL at baseline to 3.3 (0.43) mg/dL at Week 40 and to 3.3 (0.42) mg/dL at Week 64. In the active control group, mean (SD) serum phosphorus concentrations increased from 2.3 (0.26) mg/dL at baseline to 2.5 (0.34) mg/dL at Week 40 and to 2.5 (0.39) mg/dL at Week 64.

The renal phosphate reabsorptive capacity as assessed by TmP/GFR increased in the CRYSVITA-treated patients from a mean (SD) of 2.2 (0.37) mg/dL at baseline to 3.4 (0.67) mg/dL and 3.3 (0.65) mg/dL at Week 40 and Week 64, respectively. In the active control group, mean (SD) TmP/GFR decreased from 2.0 (0.33) mg/dL at Baseline to 1.8 (0.35) mg/dL at Week 40, and remained below baseline at Week 64 at 1.9 (0.49) mg/dL. Figure 1: Serum Phosphorus Concentration and Change from Baseline (mg/dL) (Mean ± SD) by Treatment Group in Children 1-12 Years in Study 1 The dotted line represents the lower limit of normal (3.2 mg/dL) for patients in Study 1.

Radiographic Evaluation of Rickets Radiographs were examined to assess XLH-related rickets using the 10-point Thacher Rickets Severity Score (RSS) and the 7-point Radiographic Global Impression of Change (RGI-C). The RSS score is assigned based on images of the wrist and knee from a single timepoint, with higher scores indicating greater rickets severity. The RGI-C score is assigned based on side-by-side comparisons of wrist and knee radiographs from two timepoints, with higher scores indicating greater improvement in radiographic evidence of rickets.

A RGI-C score of +2.0 was defined as radiographic evidence of substantial healing. In Study 1, baseline mean (SD) total RSS was 3.2 (0.98) in the CRYSVITA group and 3.2 (1.14) in the active control group. After 40 weeks of treatment with CRYSVITA, mean total RSS decreased from 3.2 to 1.1 (0.72) and from 3.2 to 2.5 (1.09) in the active control group.

LS mean (SE) RGI-C Global score was +1.9 (0.11) in the CRYSVITA group and +0.8 (0.11) in the active control group at Week 40 (see Table 10 ). At Week 40, 21 of the 29 patients in the CRYSVITA group and 2 of the 32 patients in the active control arm achieved a RGI-C global score ≥ +2.0. These findings were maintained at Week 64 as shown in Table 10 .

Table 10: Rickets Response in Children 1-12 Years Receiving CRYSVITA Every 2 Weeks in Study 1 Endpoint Timepoin… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic potential of burosumab-twza has not been evaluated in long term animal studies. Studies have not been performed to evaluate the mutagenic potential of burosumab-twza. No specific fertility studies have been performed in animals to evaluate the effects of burosumab-twza.

Toxicology studies with burosumab-twza of up to 40 weeks duration in cynomolgus monkeys did not show significant adverse effects on female reproductive organs at doses up to 16-fold human exposure at the maximum recommended human dose (MRHD) of 2 mg/kg every 2 weeks. In male monkeys, minimal mineralization of the rete testis or seminiferous tubules associated with hyperphosphatemia was observed at 3- to 9-fold human exposure at the MRHD of 2 mg/kg every 2 weeks, but semen analysis did not show any adverse effects.

13.2Animal Toxicology and/or Pharmacology In rabbits and cynomolgus monkeys, inhibition of FGF23 signaling by burosumab-twza increased serum phosphate and 1,25 dihydroxy vitamin D. Ectopic mineralization in multiple tissues and organs was observed at doses of burosumab-twza that resulted in supra-physiologic serum phosphate levels. In a study in wild type (WT) and hypophosphatemic Hyp mice, a murine model of XLH, ectopic mineralization was markedly less in Hyp mice.

In adult cynomolgus monkeys, burosumab-twza increased bone turnover, mineral content and/or mineral density and cortical thickness at 9- to 16-fold human exposure at the MRHD of 2 mg/kg every 2 weeks. Adverse effects on bone, including reductions in bone mineral density, bone mineralization and bone strength were observed in adult male monkeys at 9- to 11-fold human exposure at the MRHD of 2 mg/kg every 2 weeks. In juvenile cynomolgus monkeys, burosumab-twza increased bone turnover, mineral content and/or mineral density and/or cortical thickness at 0.2- to 2-fold clinical pediatric exposure.

Bone mineralization was decreased in a male monkey at 2-fold pediatric exposure but there was no effect on bone strength. Burosumab-twza did not affect bone development in juvenile monkeys at doses up to 2-fold pediatric exposure.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 131 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic potential of burosumab-twza has not been evaluated in long term animal studies. Studies have not been performed to evaluate the mutagenic potential of burosumab-twza. No specific fertility studies have been performed in animals to evaluate the effects of burosumab-twza.

Toxicology studies with burosumab-twza of up to 40 weeks duration in cynomolgus monkeys did not show significant adverse effects on female reproductive organs at doses up to 16-fold human exposure at the maximum recommended human dose (MRHD) of 2 mg/kg every 2 weeks. In male monkeys, minimal mineralization of the rete testis or seminiferous tubules associated with hyperphosphatemia was observed at 3- to 9-fold human exposure at the MRHD of 2 mg/kg every 2 weeks, but semen analysis did not show any adverse effects.

📄 Recent Major Changes 15 words ▾

Dosage and Administration ( 2.3 ) 4/2026 Warnings and Precautions, Hypercalcemia ( 5.3 ) 8/2025

📄 Package Label / Principal Display Panel 210 words ▾

PRINCIPAL DISPLAY PANEL - 10 mg/mL Vial NDC 42747-102-01 CRYSViTA ® (burosumab-twza) Injection 10 mg/mL 1 mL single-dose vial Kyowa Kirin, Inc. U.S. License No. 2077 PRINCIPAL DISPLAY PANEL - 10 mg/mL Vial

PRINCIPAL DISPLAY PANEL - 10 mg/mL Vial Carton NDC 42747-102-01 CRYSViTA ® (burosumab-twza) Injection 10 mg/mL For Subcutaneous Use Only Single-Dose Vial Discard Unused Portion Rx only 1 vial PRINCIPAL DISPLAY PANEL - 10 mg/mL Vial Carton

PRINCIPAL DISPLAY PANEL - 20 mg/mL Vial NDC 42747-203-01 CRYSViTA ® (burosumab-twza) Injection 20 mg/mL 1 mL single-dose vial Kyowa Kirin, Inc. U.S. License No. 2077 PRINCIPAL DISPLAY PANEL - 20 mg/mL Vial

PRINCIPAL DISPLAY PANEL - 20 mg/mL Vial Carton NDC 42747-203-01 CRYSViTA ® (burosumab-twza) Injection 20 mg/mL For Subcutaneous Use Only Single-Dose Vial Discard Unused Portion Rx only 1 vial PRINCIPAL DISPLAY PANEL - 20 mg/mL Vial Carton

PRINCIPAL DISPLAY PANEL - 30 mg/mL Vial NDC 42747-304-01 CRYSViTA ® (burosumab-twza) Injection 30 mg/mL 1 mL single-dose vial Kyowa Kirin, Inc. U.S. License No. 2077 PRINCIPAL DISPLAY PANEL - 30 mg/mL Vial

PRINCIPAL DISPLAY PANEL - 30 mg/mL Vial Carton NDC 42747-304-01 CRYSViTA ® (burosumab-twza) Injection 30 mg/mL For Subcutaneous Use Only Single-Dose Vial Discard Unused Portion Rx only 1 vial PRINCIPAL DISPLAY PANEL - 30 mg/mL 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
2.7K
Units reimbursed last 4 qtrs
6.1K
Gross reimbursed last 4 qtrs
$58.99M
Avg / prescription
$21,960.18
Avg / unit
$9,640.05
Latest quarter Q1 2026
477Rx
Fee-for-service vs managed care ⓘ
22% FFS 78% MCO
Fee-for-service · 579 Rx Managed care · 2,107 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: 26 units · 0.4 per 100k residents WI Michigan: 237 units · 2.4 per 100k residents MI New York: 370 units · 1.9 per 100k residents NY Vermont: no data reported VT New Hampshire: 29 units · 2.1 per 100k residents NH Oregon: 69 units · 1.6 per 100k residents OR Nevada: no data reported NV Wyoming: 17 units · 2.9 per 100k residents WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: 243 units · 1.9 per 100k residents IL Indiana: 104 units · 1.5 per 100k residents IN Ohio: 346 units · 2.9 per 100k residents OH Pennsylvania: 457 units · 3.5 per 100k residents PA New Jersey: 88 units · 0.9 per 100k residents NJ Massachusetts: 165 units · 2.4 per 100k residents MA California: 644 units · 1.7 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: 203 units · 3.3 per 100k residents MO Kentucky: 163 units · 3.6 per 100k residents KY West Virginia: 38 units · 2.1 per 100k residents WV Virginia: 250 units · 2.9 per 100k residents VA Maryland: no data reported MD Connecticut: 95 units · 2.6 per 100k residents CT Rhode Island: no data reported RI Arizona: 77 units · 1.0 per 100k residents AZ New Mexico: no data reported NM Kansas: 43 units · 1.5 per 100k residents KS Arkansas: 43 units · 1.4 per 100k residents AR Tennessee: 190 units · 2.7 per 100k residents TN North Carolina: 746 units · 6.9 per 100k residents NC South Carolina: 69 units · 1.3 per 100k residents SC Delaware: no data reported DE Oklahoma: 36 units · 0.9 per 100k residents OK Louisiana: 145 units · 3.2 per 100k residents LA Mississippi: 39 units · 1.3 per 100k residents MS Alabama: 86 units · 1.7 per 100k residents AL Georgia: 378 units · 3.4 per 100k residents GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 405 units · 1.3 per 100k residents TX Florida: 318 units · 1.4 per 100k residents FL
Units reimbursed · per 100k residents
0.46.9
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 North Carolina 6.9 /100k
2 Kentucky 3.6 /100k
3 Pennsylvania 3.5 /100k
4 Georgia 3.4 /100k
5 Missouri 3.3 /100k
6 Louisiana 3.2 /100k
7 Ohio 2.9 /100k
8 Wyoming 2.9 /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.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Crysvita — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Crysvita. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$21.43M
Claims incl. refills
711
Beneficiaries
196
Spend / beneficiary
$109,347.80
Spend / claim
$30,143.70
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for CRYSVITA (this brand).

Top reported reactions

Blood Phosphorus Decreased584
Pain391
Arthralgia376
Pain In Extremity353
Restless Legs Syndrome276
Headache273
Fatigue252

Age at onset

Infant1
Child3
Adolescent1
Adult5
Elderly4

Reporter sex

6,315 reports
Male · 45%
Female · 55%

Serious outcomes

Hospitalization463
Death42
Disabling22
Life-threatening10
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 1,336 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

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) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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: this package is listed as actively marketed, with no marketing end date reported by Kyowa Kirin, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Kyowa Kirin, 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 J0584 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.
← 42747-0102-01 · Kyowa 42747-0304-01 · Kyowa →
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.