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Kygevvi doxecitine and doxribtimine 2 g; 2 g Powder, For Solution, 30 packets — NDC 50474-0350-30 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Kygevvi doxecitine and doxribtimine 2 g; 2 g Powder, For Solution, 30 packets — NDC 50474-350-30 (Billing 50474-0350-30)

by UCB, Inc. · 30 PACKET in 1 CARTON / 1 POWDER, FOR SOLUTION in 1 PACKET

This is a package of 30 packets of Kygevvi doxecitine and doxribtimine 2 g; 2 g Powder, For Solution from UCB, Inc., marketed since Mar 2026 and currently FDA-listed. It is this product's only package size.

NDC 50474-0350-30
🏷️ FDA NDC (as labeled) 50474-350-30 billing pads the product segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 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 50474-350-30 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
50474 labeler · 350 product · 30 package
Package marketed since
Mar 1, 2026
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Billing quantity
30 EA per package
Barcode (UPC-A, from the NDC)
3 5047435030 0
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 50474-350-30
Product NDC 50474-350
11-digit billing NDC 50474035030
NCPDP billing unit EA — each (per item)
RxCUI 2737535, 2737541
UNII 0W860991D6, VC2W18DGKR
Application # NDA219792
SPL Set ID 7d5ce670-9314-4fd7-8b0a-1447910dcf9e
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2026-03-01
Route ORAL
Dosage form POWDER, FOR SOLUTION
Substance DOXECITINE; DOXRIBTIMINE

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

GPI-14 30909902203020
GCN Seq No 088409
GCN 58485
HICL code 050999
Ingredient (HICL) Doxecitine/Doxribtimine
HIC1 code Z
Therapeutic class — broad (HIC1) Body As A Whole
HIC2 code ZA
Therapeutic class — intermediate (HIC2) Drugs Having Action On Wide-Spread Tissue (Cont 1)
HIC3 code ZAL
Therapeutic class — specific (HIC3) Genetic Disorder Therapy - Pyrimidine Analogs
AHFS code 92:92.00.00
AHFS class Other Miscellaneous Therapeutic Agents
FDB label name KYGEVVI 4 GM (2GM-2GM) POWD PK
FDB brand name Kygevvi
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 088409
  • GCN: 58485
  • GPI-14 (Medi-Span): 30909902203020
  • HICL (First Databank): 050999
  • AHFS class code: 92:92.00.00
  • RxCUI (RxNorm): 2737535
Why two NDCs? The FDA registers this code as 50474-350-30 — 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 → 50474-0350-30. 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 Various alimentary tract and metabolism products class.

Drug family (ATC) Various alimentary tract and metabolism products
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 KYGEVVI 4 GM (2GM-2GM) POWD PK Ingredient Doxecitine/Doxribtimine

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 No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
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.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
50474-0350-30 You're viewing this Main listing 30 PACKET in 1 CARTON / 1 POWDER, FOR SOLUTION in 1 PACKET 2026-03-01 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Kygevvi 2 g/1; 2 gthis 50474-0350-30 UCB, 30 packets — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
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 & generic status

🏛️
2025
First FDA approval
Nov 2025
📍
2026
Currently FDA-listed
1 year listed
🛡️
2040
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Aug 2040. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Nov 3, 2025 RLD RS ⏳ ~13.9 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 11649259 — method of use (U-4358)
US 10471087 — method of use (U-4358)
Exclusivity NCE
2025 2027 2029 2031 2033 2035 2037 2039
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (2)
PatentTypeUse codeExpires
US 11649259 ↗ Method of use U-4358 Aug 19, 2040
US 10471087 ↗ Method of use U-4358 Aug 7, 2036
FDA exclusivity
CodeWhat it grantsExpires
NCENew Chemical Entity (5-year)Nov 3, 2030
Common questions
Is there a generic version of KYGEVVI 4 GM (2GM-2GM) POWD PK?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for KYGEVVI 4 GM (2GM-2GM) POWD PK. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Aug 2040 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, 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 Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color white
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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.

A current SPL was checked, but it does not contain a structured or narrative inactive-ingredient list for this product. This does not mean the product has no inactive ingredients.
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

LabelerUCB, Inc.
Application holderUCB INC
FDA applicationNDA219792 (NDA)
Labeler code50474
First marketedMar 2026
Product typeHuman Prescription Drug
Portfolio45 products on file

More NDCs from UCB, Inc. labeler code 50474

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 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🧬 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 📄 Patient Package Insert 📖 Instructions for Use 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 72 words ▾

1 INDICATIONS AND USAGE KYGEVVI is indicated for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and pediatric patients with an age of symptom onset on or before 12 years. KYGEVVI is a combination of doxecitine and doxribtimine, both pyrimidine nucleosides, indicated for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and pediatric patients with an age of symptom onset on or before 12 years. ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Obtain baseline transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) levels in all patients prior to treatment initiation. ( 2.1 ) Recommended dosage ( 2.2 ): KYGEVVI Dosage Level KYGEVVI Dosage (mg/kg/day) Starting 260 mg/kg/day (consisting of 130 mg doxecitine and 130 mg doxribtimine) Intermediate 520 mg/kg/day (consisting of 260 mg doxecitine and 260 mg doxribtimine) Maintenance 800 mg/kg/day (consisting of 400 mg doxecitine and 400 mg doxribtimine) Titrate to the next dosage level based on tolerability after a minimum of 2 weeks at the current dosage level.

( 2.2 ) Administer KYGEVVI orally in 3 equally divided doses with food. ( 2.2 ) See full prescribing information for dosage and administration modifications, monitoring, and preparation and administration instructions. ( 2.4 ) Use KYGEVVI only with ZX2000 administration kit.

( 2.4 )

2.1Important Recommendation Prior to KYGEVVI Treatment Initiation Obtain baseline liver transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and total bilirubin levels in patients prior to treatment initiation with KYGEVVI [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ] .

2.2Recommended Dosage The recommended dosage of KYGEVVI is based on the patient's weight (Table 1). Titrate to the next dosage level based on tolerability after a minimum of 2 weeks at the current dosage level. Table 1: Recommended Starting, Intermediate, and Maintenance Dosage of KYGEVVI KYGEVVI Dosage Level KYGEVVI Dosage (mg/kg/day) Starting 260 mg/kg/day (consisting of 130 mg doxecitine and 130 mg doxribtimine) Intermediate 520 mg/kg/day (consisting of 260 mg doxecitine and 260 mg doxribtimine) Maintenance 800 mg/kg/day (consisting of 400 mg doxecitine and 400 mg doxribtimine) Administer KYGEVVI orally in 3 equally divided doses approximately 6 hours apart (plus or minus 2 hours) with food [see Clinical Pharmacology (12.3) ] .

After calculating the daily dose, use Table 2 to determine the required number of KYGEVVI packets, volume of water needed to reconstitute the powder from the packet(s), and individual volume that is administered 3 times a day [see Dosage and Administration (2.4) ].

2.3Dosage and Administration Modifications and Monitoring Liver Test Abnormalities If signs or symptoms consistent with liver injury are observed, interrupt treatment with KYGEVVI until liver transaminase (ALT, AST) and total bilirubin levels have either returned to baseline or stabilized at a new baseline value. Consider re-starting KYGEVVI at the last tolerated dose and increase the dose based on tolerability [see Dosage and Administration (2.2) ] . Consider permanently discontinuing KYGEVVI if signs or symptoms consistent with liver injury persist or worsen.

Monitor liver transaminases and total bilirubin levels yearly and as clinically indicated [see Warnings and Precautions (5.1) ] . Gastrointestinal Based on the severity of the diarrhea and/or vomiting, reduce the dose of KYGEVVI or interrupt treatment until diarrhea and/or vomiting improves or returns to baseline. Consider re-starting KYGEVVI at the last tolerated dose and increase the dose based on tolerability [see Dosage and Administration (2.2) ] .

For persistent or recurring diarrhea and/or vomiting, consider discontinuing KYGEVVI permanently. Monitor for dehydration and treat promptly with electrolyte replacement [see Warnings and Precautions (5.2) ] .

2.4Preparation and Administration Instructions Use Table 2 for preparation and administration information. Table 2: Recommended Dosage - Preparation and Dosing by Daily-Dose Range Total Daily Dose (mg/day) Volume of Solution (mL) (administered 3 times per day) Total mL of Water for Reconstitution Total Number of KYGEVVI Packets for Reconstitution 750 – 824 2.5 40 1 825 – 974 3 975 – 1,124 3.5 1,125 – 1,299 4 1,300 – 1,449 4.5 1,450 – 1,649 5 1,650 – 1,949 6 1,950 – 2,249 7 2,250 – 2,549 8 2,550 – 2,849 9 2,850… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 40 words ▾

3 DOSAGE FORMS AND STRENGTHS Powder for oral solution: 2 g doxecitine and 2 g doxribtimine as white to off-white powder in a single use packet. Powder for oral solution: 2 g doxecitine and 2 g doxribtimine. ( 3 )

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~1 min read ▾

5 WARNINGS AND PRECAUTIONS Elevated Liver Transaminase Levels : Obtain baseline liver transaminase (ALT, AST) and total bilirubin levels prior to treatment initiation with KYGEVVI. If signs or symptoms consistent with liver injury are observed, interrupt treatment. Consider permanently discontinuing KYGEVVI if signs/symptoms consistent with liver injury persist or worsen.

Monitor patients yearly and as clinically indicated. ( 5.1 ) Gastrointestinal Adverse Reactions : Reduce KYGEVVI dosage or interrupt treatment based on severity of diarrhea and/or vomiting. If persistent severe diarrhea and/or vomiting occurs, consider discontinuing KYGEVVI permanently.

( 5.2 )

5.1Elevated Liver Transaminase Levels Elevated liver transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels were reported in patients treated with KYGEVVI [see Adverse Reactions (6.1) ] . In Study 1, two patients permanently discontinued treatment with KYGEVVI upon recurrence of elevated liver enzymes after a rechallenge at a reduced dose. Obtain baseline liver transaminase (ALT, AST) and total bilirubin levels in patients prior to treatment initiation with KYGEVVI.

If signs or symptoms consistent with liver injury are observed, interrupt treatment with KYGEVVI until liver transaminase (ALT, AST) and total bilirubin levels have either returned to baseline or stabilized at a new baseline value. Consider permanently discontinuing KYGEVVI if signs or symptoms consistent with liver injury persist or worsen. Monitor liver transaminases and total bilirubin levels yearly and as clinically indicated [see Dosage and Administration (2.3) ] .

5.2Gastrointestinal Adverse Reactions Diarrhea and vomiting leading to hospitalization, dose reduction, and permanent discontinuation were reported in patients treated with KYGEVVI [see Adverse Reactions (6.1) ] . Based on the severity of the diarrhea and/or vomiting, reduce the dosage of KYGEVVI or interrupt treatment until diarrhea and/or vomiting improves or returns to baseline. Consider restarting KYGEVVI at the last tolerated dose, and increase the dose as tolerated.

For persistent or recurring diarrhea and/or vomiting, consider discontinuing KYGEVVI permanently and provide supportive care with electrolyte repletion as clinically indicated.

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Elevated Liver Transaminase Levels [see Warnings and Precautions (5.1) ] Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence ≥5%) are diarrhea, abdominal pain (including abdominal pain upper), vomiting, alanine aminotransferase increased (ALT), and aspartate aminotransferase increased (AST). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 1-844-599-2273 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. The safety of KYGEVVI was evaluated in a prospective, open-label, single-arm study in pediatric and adult patients with genetically confirmed TK2d previously treated with pyrimidine nucleosides (Trial 1). Additional safety information was derived from retrospective chart review studies (Study 1, Study 2) and from an expanded access program [see Clinical Studies (14) ] .

Permanent discontinuation of KYGEVVI due to an adverse reaction occurred in 9% of patients (Trial 1, Study 1, and Study 2). The adverse reactions which resulted in permanent discontinuation of KYGEVVI in >2% of patients were diarrhea (3%) and elevated liver enzymes (3%). In the expanded access program, diarrhea resulted in permanent discontinuation in 2 patients.

Dose reductions of KYGEVVI due to an adverse reaction occurred in 22% of patients (Trial 1, Study 1, and Study 2). Adverse reactions which required dose reduction in >2% of patients included diarrhea (21%) and abdominal pain (3%). Diarrhea resulted in hospitalization in 2 pediatric patients (Study 1 and expanded access program).

Adverse Reactions from Trial 1 A total of 47 patients, between the ages of 0.7 and 74 years of age at enrollment, received KYGEVVI or pyrimidine nucleosides dosages up to 800 mg/kg/day [see Clinical Studies (14) ] . KYGEVVI is not approved for use in patients with an age of TK2d symptom onset > 12 years. The mean (SD) KYGEVVI or pyrimidine nucleosides exposure during Trial 1 was 6.6 (2) years.

Table 3 summarizes the adverse reactions reported in ≥ 5% patients treated with KYGEVVI or pyrimidine nucleosides. Table 3: Adverse Reactions That Occurred in ≥5% Adult and Pediatric Patients with TK2d Treated with KYGEVVI or Pyrimidine Nucleosides (Trial 1) Adverse reactions Treated Patients (N=47) n (%) Diarrhea 34 (72) Abdominal pain (including abdominal pain upper) 11 (23) Vomiting 10 (21) Alanine aminotransferase increased (ALT) 10 (21) Aspartate aminotransferase increased (AST) 8 (17) Adverse reactions, vomiting and elevated liver transaminases, were observed in a higher percentage of pediatric patients than in adult patients.

In Trial 1, vomiting occurred in 28% (9/32) of pediatric patients compared to 7% (1/15) of adult patients. Elevated liver transaminases occurred in 25% (8/32) for ALT and 22% (7/32) for AST of pediatric patients compared to 13% (2/15) for ALT and 7% (1/15) for AST of adult patients. Laboratory Adverse Reaction Elevated liver enzymes have been observed as a clinical manifestation of TK2d.

In Trial 1 and Study 1, elevations in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) occurred in 28% (14/50) and 22% (11/50) of patients respectively. In Trial 1, of all the patients who started treatment with elevated AST/ALT at baseline, 5% had last post-baseline ALT values that were higher severity than the baseline severity while continuing treatment [see Warnings and Precautions (5.1) ] .

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary There are no available data on KYGEVVI use during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Endogenous pyrimidine nucleosides are transported across the placenta. There are risks for adverse maternal and fetal outcomes during pregnancy with mitochondrial myopathies, including TK2 deficiency ( see Clinical Considerations ).

In animal reproduction studies, oral administration of doxecitine and doxribtimine to pregnant rats and rabbits during organogenesis resulted in maternal and fetal toxicities in the rabbit at dose exposures 1233 and 811 times the maximum recommended human dose (MRHD) of 400 mg/kg/day doxecitine and 400 mg/kg/day doxribtimine, respectively, based on plasma exposure, but were not observed in the rat ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20% respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Mitochondrial myopathies are associated with increased adverse perinatal outcomes, including preterm birth, pre-eclampsia and gestational diabetes. Data Animal Data In an embryofetal development study in pregnant rats, once daily oral doses of 200, 600, and 2000 mg/kg/day doxecitine and doxribtimine were administered throughout organogenesis between gestation day (GD) 7 to 17.

No maternal or embryofetal toxicity was observed up to 2000 mg/kg/day (1223 times and 425 times the MRHD of doxecitine and doxribtimine, respectively, based on plasma exposure). In an embryofetal development study in pregnant rabbits, once daily oral doses of 200, 600, and 2000 mg/kg/day doxecitine and doxribtimine were administered throughout organogenesis between GD 7 and GD 19. Marked maternal toxicity and fetal malformations (dilated aorta with an associated narrow pulmonary trunk) were observed at the highest dose (1233 times and 811 times the MRHD of doxecitine and doxribtimine, respectively, based on plasma exposure).

The maternal and fetal no observed adverse effect level (NOAEL) in rabbits (600 mg/kg/day) was associated with maternal plasma exposures 729 times and 126 times the MRHD of 400 mg/kg/day doxecitine and 400 mg/kg/day doxribtimine, respectively.

8.2Lactation Risk Summary There are no data on the presence of doxecitine and doxribtimine or its metabolites in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Data from published literature reports the presence of nucleosides and nucleotides in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for KYGEVVI and any potential adverse effects on the breastfed infant from KYGEVVI or from the underlying maternal condition.

8.4Pediatric Use The safety and effectiveness of KYGEVVI for the treatment of thymidine kinase 2 deficiency (TK2d) have been established in pediatric patients with an age of symptom onset on or before 12 years. Use of KYGEVVI for this indication in this population is supported by evidence from two retrospective studies (Study 1, Study 2), one open-label study (Trial 1), and an expanded access program in which a total of 68 patients 0.7 years of age to less than 17 years of age were treated [see Clinical Studies (14) ] .

In Trial 1, compared to adults, a higher percentage of pediatric patients experienced adverse reactions of vomiting and elevated liver transaminases [see Adverse Reactions (6.1) ] . Serious adverse reactions in the pediatric population included hospitalization due to diarrhea in two patients [see Warnings and Precautions (5.2) ] .… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary There are no available data on KYGEVVI use during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Endogenous pyrimidine nucleosides are transported across the placenta. There are risks for adverse maternal and fetal outcomes during pregnancy with mitochondrial myopathies, including TK2 deficiency ( see Clinical Considerations ).

In animal reproduction studies, oral administration of doxecitine and doxribtimine to pregnant rats and rabbits during organogenesis resulted in maternal and fetal toxicities in the rabbit at dose exposures 1233 and 811 times the maximum recommended human dose (MRHD) of 400 mg/kg/day doxecitine and 400 mg/kg/day doxribtimine, respectively, based on plasma exposure, but were not observed in the rat ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20% respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Mitochondrial myopathies are associated with increased adverse perinatal outcomes, including preterm birth, pre-eclampsia and gestational diabetes. Data Animal Data In an embryofetal development study in pregnant rats, once daily oral doses of 200, 600, and 2000 mg/kg/day doxecitine and doxribtimine were administered throughout organogenesis between gestation day (GD) 7 to 17.

No maternal or embryofetal toxicity was observed up to 2000 mg/kg/day (1223 times and 425 times the MRHD of doxecitine and doxribtimine, respectively, based on plasma exposure). In an embryofetal development study in pregnant rabbits, once daily oral doses of 200, 600, and 2000 mg/kg/day doxecitine and doxribtimine were administered throughout organogenesis between GD 7 and GD 19. Marked maternal toxicity and fetal malformations (dilated aorta with an associated narrow pulmonary trunk) were observed at the highest dose (1233 times and 811 times the MRHD of doxecitine and doxribtimine, respectively, based on plasma exposure).

The maternal and fetal no observed adverse effect level (NOAEL) in rabbits (600 mg/kg/day) was associated with maternal plasma exposures 729 times and 126 times the MRHD of 400 mg/kg/day doxecitine and 400 mg/kg/day doxribtimine, respectively.

🧒 Pediatric Use 141 words ▾

8.4Pediatric Use The safety and effectiveness of KYGEVVI for the treatment of thymidine kinase 2 deficiency (TK2d) have been established in pediatric patients with an age of symptom onset on or before 12 years. Use of KYGEVVI for this indication in this population is supported by evidence from two retrospective studies (Study 1, Study 2), one open-label study (Trial 1), and an expanded access program in which a total of 68 patients 0.7 years of age to less than 17 years of age were treated [see Clinical Studies (14) ] .

In Trial 1, compared to adults, a higher percentage of pediatric patients experienced adverse reactions of vomiting and elevated liver transaminases [see Adverse Reactions (6.1) ] . Serious adverse reactions in the pediatric population included hospitalization due to diarrhea in two patients [see Warnings and Precautions (5.2) ] .

🧓 Geriatric Use 30 words ▾

8.5Geriatric Use Clinical studies of KYGEVVI did not include sufficient number of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Administration of KYGEVVI is intended to incorporate the pyrimidine nucleosides, deoxycytidine and deoxythymidine, into skeletal muscle mitochondrial deoxyribonucleic acid (DNA). This action restores mitochondrial DNA copy number in TK2d mutant mice.

12.2Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of KYGEVVI have not been fully characterized.

12.3Pharmacokinetics Following oral administration of doxecitine and doxribtimine in healthy adult subjects, the baseline-adjusted maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) increased in a less than dose proportional manner for doxecitine at doses ranging from 43 mg/kg to 133 mg/kg and more than dose proportional manner for doxribtimine at doses ranging from 43 mg/kg to 133 mg/kg. There is minimal or no accumulation of doxecitine and doxribtimine following multiple dose administrations.

Following oral administration of doxecitine and doxribtimine at the recommended maintenance dosage of 800 mg/kg/day under fed conditions in 18 TK2d pediatric and adult subjects, the estimated baseline-unadjusted geometric mean C max at steady state was 12 ng/mL and 19 ng/mL for doxecitine and doxribtimine, respectively, and the geometric mean AUC from time 0 to 24 hours (AUC 0-24hr ) was 108 ng∙h/mL and 191 ng∙h/mL for doxecitine and doxribtimine, respectively. Inter-subject variability (geometric CV%) in C max and AUC 0-24h values of doxecitine and doxribtimine were greater than 70%.

Absorption The absolute bioavailability of doxecitine and doxribtimine following oral administration has not been determined. The median time to peak plasma concentration (T max ) was approximately 2 hours for doxecitine and 4 hours for doxribtimine. Effect of Food Following an oral administration of 133 mg/kg doxecitine and 133 mg/kg doxribtimine with a high-fat, high-calorie meal in healthy adult subjects, baseline-adjusted plasma C max and AUC 0-t increased by 79% and 137%, respectively, for doxecitine; and increased by 27% and 74%, respectively, for doxribtimine, compared to fasted conditions [see Dosage and Administration (2.2) ] .

Distribution In vitro plasma protein binding of doxecitine and doxribtimine was less than 10% over the concentration range between 0.23 mcg/mL and 23 mcg/mL. Elimination The mean half-life was approximately 1 hour for doxecitine and 5 hours for doxribtimine following a single oral administration of 133 mg/kg doxecitine and 133 mg/kg doxribtimine under fed conditions in healthy adult subjects. Metabolism Doxecitine and doxribtimine are primarily degraded (catabolized) by cytidine deaminase and thymidine phosphorylase, respectively, to their nucleobases and the 2-deoxy-α-D-ribose 1-phosphate moiety.

Intermediate products of doxecitine catabolism are deoxyuridine, uracil, and dihydrouracil with the end products β-alanine, ammonia, and carbon dioxide (CO 2 ). Thymine, the pyrimidine nucleobase of doxribtimine, is subsequently catabolized to dihydrothymine and ultimately to γ-amino-isobutyric acid and CO 2 . Doxecitine and doxribtimine are not known to be metabolized by cytochrome P450 (CYP) isoforms.

Excretion Urinary excretion of intact doxecitine and doxribtimine was <1% of the dose in healthy subjects following an oral administration of doxecitine and doxribtimine. Specific Populations Male and Female Patients The pharmacokinetics of doxecitine and doxribtimine were not significantly different between male and female subjects. Patients with Renal Impairment The pharmacokinetics of doxecitine and doxribtimine in subjects with moderate (estimated glomerular filtration rate [eGFR] ≥ 30 and ≤ 59 mL/min/1.73 m 2 ) or severe (eGFR ≥ 15 and ≤ 29 mL/min/1.73 m 2 ) renal impairment were compared with healthy subjects with normal renal function following a single oral administration of 133 mg/kg doxecitine and 133 mg/k… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 35 words ▾

12.1Mechanism of Action Administration of KYGEVVI is intended to incorporate the pyrimidine nucleosides, deoxycytidine and deoxythymidine, into skeletal muscle mitochondrial deoxyribonucleic acid (DNA). This action restores mitochondrial DNA copy number in TK2d mutant mice.

📦 How Supplied / Storage and Handling 145 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied KYGEVVI is supplied as follows: Package 1 of 2 NDC 50474-350-01: Each single use packet contains 4 g of KYGEVVI as a white to off-white powder (2 g doxecitine and 2 g doxribtimine) NDC 50474-350-30: Carton contains 30 packets Package 2 of 2 The ZX2000 administration kit for use with KYGEVVI is supplied separately and contains the following: One dosing system (includes mixing bottle and dosing cup) Two 10 mL oral syringes Two spare seals Storage and Handling Store KYGEVVI packets at 20°C to 25°C (68°F to 77°F); excursion permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Store reconstituted KYGEVVI solution at controlled room temperature or in the refrigerator. Discard KYGEVVI solution 16 hours after reconstitution or after taking or giving the 3 doses, whichever comes first [see Dosage and Administration (2.5) ].

📦 Storage and Handling 63 words ▾

Storage and Handling Store KYGEVVI packets at 20°C to 25°C (68°F to 77°F); excursion permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store reconstituted KYGEVVI solution at controlled room temperature or in the refrigerator. Discard KYGEVVI solution 16 hours after reconstitution or after taking or giving the 3 doses, whichever comes first [see Dosage and Administration (2.5) ].

📋 Description 125 words ▾

11 DESCRIPTION KYGEVVI is a combination of doxecitine and doxribtimine, both of which are pyrimidine nucleosides. KYGEVVI is a powder for oral solution. Both doxecitine and doxribtimine are white to off-white powders and soluble in water.

Doxecitine The chemical name of doxecitine is 4-Amino-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one. The molecular formula is C 9 H 13 N 3 O 4 and the molecular weight is 227.22 g/mol. The chemical structure is: Doxribtimine The chemical name of doxribtimine is 1-((2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione.

The molecular formula is C 10 H 14 N 2 O 5 and the molecular weight is 242.23 g/mol. The chemical structure is: Each packet of KYGEVVI powder contains 2 grams doxecitine and 2 grams doxribtimine. The inactive ingredients are colloidal silicon dioxide and magnesium stearate.

Chemical Structure Chemical Structure

💬 Information for Patients 153 words ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Preparation and Administration Instructions of KYGEVVI Solution Advise the patient to use the ZX2000 administration kit provided by the pharmacy to prepare and administer KYGEVVI solution. Inform the patient to prepare a one-day supply of the KYGEVVI solution each morning and take each individual dose with food [see Dosage and Administration (2.4) ].

Elevated Liver Transaminase Levels Inform the patient that KYGEVVI may cause liver enzyme elevations. Instruct the patient to promptly report loss of appetite, abdominal pain, dark urine, or jaundice to his/her healthcare provider [see Warnings and Precautions (5.1) ]. Gastrointestinal Adverse Reactions Inform the patient that KYGEVVI may cause diarrhea and vomiting.

Advise the patient to promptly report to his/her healthcare provider diarrhea and vomiting that lasts longer than a few days while taking KYGEVVI [see Warnings and Precautions (5.2) ].

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Following oral administration of doxecitine and doxribtimine in healthy adult subjects, the baseline-adjusted maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) increased in a less than dose proportional manner for doxecitine at doses ranging from 43 mg/kg to 133 mg/kg and more than dose proportional manner for doxribtimine at doses ranging from 43 mg/kg to 133 mg/kg. There is minimal or no accumulation of doxecitine and doxribtimine following multiple dose administrations.

Following oral administration of doxecitine and doxribtimine at the recommended maintenance dosage of 800 mg/kg/day under fed conditions in 18 TK2d pediatric and adult subjects, the estimated baseline-unadjusted geometric mean C max at steady state was 12 ng/mL and 19 ng/mL for doxecitine and doxribtimine, respectively, and the geometric mean AUC from time 0 to 24 hours (AUC 0-24hr ) was 108 ng∙h/mL and 191 ng∙h/mL for doxecitine and doxribtimine, respectively. Inter-subject variability (geometric CV%) in C max and AUC 0-24h values of doxecitine and doxribtimine were greater than 70%.

Absorption The absolute bioavailability of doxecitine and doxribtimine following oral administration has not been determined. The median time to peak plasma concentration (T max ) was approximately 2 hours for doxecitine and 4 hours for doxribtimine. Effect of Food Following an oral administration of 133 mg/kg doxecitine and 133 mg/kg doxribtimine with a high-fat, high-calorie meal in healthy adult subjects, baseline-adjusted plasma C max and AUC 0-t increased by 79% and 137%, respectively, for doxecitine; and increased by 27% and 74%, respectively, for doxribtimine, compared to fasted conditions [see Dosage and Administration (2.2) ] .

Distribution In vitro plasma protein binding of doxecitine and doxribtimine was less than 10% over the concentration range between 0.23 mcg/mL and 23 mcg/mL. Elimination The mean half-life was approximately 1 hour for doxecitine and 5 hours for doxribtimine following a single oral administration of 133 mg/kg doxecitine and 133 mg/kg doxribtimine under fed conditions in healthy adult subjects. Metabolism Doxecitine and doxribtimine are primarily degraded (catabolized) by cytidine deaminase and thymidine phosphorylase, respectively, to their nucleobases and the 2-deoxy-α-D-ribose 1-phosphate moiety.

Intermediate products of doxecitine catabolism are deoxyuridine, uracil, and dihydrouracil with the end products β-alanine, ammonia, and carbon dioxide (CO 2 ). Thymine, the pyrimidine nucleobase of doxribtimine, is subsequently catabolized to dihydrothymine and ultimately to γ-amino-isobutyric acid and CO 2 . Doxecitine and doxribtimine are not known to be metabolized by cytochrome P450 (CYP) isoforms.

Excretion Urinary excretion of intact doxecitine and doxribtimine was <1% of the dose in healthy subjects following an oral administration of doxecitine and doxribtimine. Specific Populations Male and Female Patients The pharmacokinetics of doxecitine and doxribtimine were not significantly different between male and female subjects. Patients with Renal Impairment The pharmacokinetics of doxecitine and doxribtimine in subjects with moderate (estimated glomerular filtration rate [eGFR] ≥ 30 and ≤ 59 mL/min/1.73 m 2 ) or severe (eGFR ≥ 15 and ≤ 29 mL/min/1.73 m 2 ) renal impairment were compared with healthy subjects with normal renal function following a single oral administration of 133 mg/kg doxecitine and 133 mg/kg doxribtimine.

Baseline-adjusted plasma doxecitine AUC was 122% and 66% higher in subjects with moderate and severe renal impairment, respectively, compared with matched control subjects with normal renal function. Baseline adjusted plasma doxribtimine AUC was 447% and 148% higher in subjects with moderate and severe renal impairment, respectively, compared with matched control subjects with normal renal function [see Use in Specific Populations (8.6) ] . Patients with Hepati… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 23 words ▾

12.2Pharmacodynamics The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of KYGEVVI have not been fully characterized.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES The efficacy of KYGEVVI for the treatment of patients with TK2d, with an age of symptom onset on or before 12 years of age, was established based on data from one Phase 2 clinical study (Trial 1), two retrospective chart review studies (Study 1, Study 2), and an expanded access program. The survival in treated patients was compared with survival in an untreated external control group comprised of untreated patients from published literature and Study 2. Trial 1 (NCT03845712) is a prospective, open-label, single-arm study in 47 patients with genetically confirmed TK2d previously treated with pyrimidine nucleosides.

Thirty-eight of these 47 patients have an age of TK2d symptom onset ≤12 years; none of the 38 patients discontinued treatment. The initial oral dose of KYGEVVI was matched to the patient's pyrimidine nucleoside dose of 260-800 mg/kg/day upon entering the study in patients with an age of TK2d symptom onset ≤ 12 years, and dosage was titrated, as needed, over a maximum of 4 weeks to the maintenance dose of 800 mg/kg/day. Study 1 (NCT03701568) was a retrospective chart review study in 38 patients with genetically confirmed TK2d treated with pyrimidine nucleosides.

Twenty-nine of these patients had an age of TK2d symptom onset ≤12 years; none of the 29 patients discontinued treatment. Thirty-five of these 38 patients were later enrolled in Trial 1 to receive treatment with KYGEVVI and one was later enrolled in Study 2. KYGEVVI was not administered in Study 1.

Patients enrolled in Study 1 were receiving pyrimidine nucleoside treatment at doses 160-800 mg/kg/day. Study 2 (NCT05017818) was a retrospective chart review study in 61 patients with genetically confirmed TK2d (43 untreated patients and 18 patients treated with pyrimidine nucleoside therapy). Nine of these 61 patients were also included in the expanded access program and 1 patient was included in Study 1.

Twenty-seven of the 43 untreated patients had an age of TK2d symptom onset ≤12 years, and 13 of the 18 treated patients had an age of TK2d symptom onset ≤12 years. Twenty-two untreated patients were included in the untreated external control group used to evaluate survival. Of the 18 treated patients, 6 (33%) discontinued treatment due to an adverse reaction.

KYGEVVI was not administered in Study 2. Patients enrolled in Study 2 were receiving pyrimidine nucleoside treatment at doses 200-1200 mg/kg/day. Expanded Access Program The expanded access program data included 43 patients receiving KYGEVVI; 9 patients were included in Study 2.

Efficacy Results A total of 82 patients with genetically confirmed TK2d and the age of symptom onset ≤12 years were treated with KYGEVVI or pyrimidine nucleosides. Efficacy was assessed by comparing overall survival in the treated patients to an external control group of untreated patients matched to treated patients using age of TK2d symptom onset (≤ 2 years or >2 to ≤ 12 years). A total of 78 matched pairs were identified.

Of the 78 treated patients included in the survival analysis, 54% were male and 36% were of Hispanic or Latino ethnicity. Eighty-two percent of patients were White, 4% Black or African American, 5% Asian, 3% Other, and 1% American Indian or Alaska Native. The median age of TK2d symptom onset was 1.5 years (range: 0.01 to 12 years).

The median duration of treatment was 4 years (range: 1 day to 12 years) and the median dose received was 762 mg/kg/day (range: 260 to 800 mg/kg/day). Treatment reduced the overall risk of death from treatment start by approximately 86% (95% CI: 61%, 96%) (Table 4, Figure 1). Table 4: Overall Survival in Patients with TK2d (Age of Symptom Onset ≤12 Years) Treated with KYGEVVI Versus Matched Untreated Patients (External Control) Treated patients were originally from Trial 1 (n=9), Study 1 (n=27), Study 2 (n=11), and the expanded access program (n=31).

Untreated patients were from published literature (n=57) and Study 2 (n=21). Treated Patients (n= 78) Matched Untreate… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 168 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Animal studies to evaluate the carcinogenic potential of doxecitine and doxribtimine have not been conducted. Mutagenesis Doxecitine and doxribtimine were not mutagenic or clastogenic in an in vitro bacterial reverse mutation (Ames) and an in vivo rat micronucleus assay. Doxecitine and doxribtimine induced chromosomal aberrations in the absence of metabolic activation in an in vitro cytogenetic study in human lymphocytes.

One compound (alpha-hydroxythymidine) originating from a doxribtimine starting material and present in the final drug product was positive for mutagenesis in the Ames assay and positive for clastogenesis in human peripheral lymphocytes when tested alone. Impairment of Fertility Doxecitine and doxribtimine had no effect on male or female fertility or early embryonic development at doses up to 2000 mg/kg/day in rats (1131 times and 1223 times the MRHD in males and females respectively for 400 mg/kg/day doxecitine and 1056 times and 425 times the MRHD in males and females respectively for 400 mg/kg/day doxribtimine, based on plasma exposure).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 165 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Animal studies to evaluate the carcinogenic potential of doxecitine and doxribtimine have not been conducted. Mutagenesis Doxecitine and doxribtimine were not mutagenic or clastogenic in an in vitro bacterial reverse mutation (Ames) and an in vivo rat micronucleus assay. Doxecitine and doxribtimine induced chromosomal aberrations in the absence of metabolic activation in an in vitro cytogenetic study in human lymphocytes.

One compound (alpha-hydroxythymidine) originating from a doxribtimine starting material and present in the final drug product was positive for mutagenesis in the Ames assay and positive for clastogenesis in human peripheral lymphocytes when tested alone. Impairment of Fertility Doxecitine and doxribtimine had no effect on male or female fertility or early embryonic development at doses up to 2000 mg/kg/day in rats (1131 times and 1223 times the MRHD in males and females respectively for 400 mg/kg/day doxecitine and 1056 times and 425 times the MRHD in males and females respectively for 400 mg/kg/day doxribtimine, based on plasma exposure).

📄 Patient Package Insert ~3 min read ▾

PATIENT INFORMATION KYGEVVI (KY-JEH-vee) (doxecitine and doxribtimine) powder, for oral solution This Patient Information has been approved by the U.S. Food and Drug Administration. Issued: 11/2025 What is KYGEVVI?

KYGEVVI is a prescription medicine used for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and children with a symptom onset on or before 12 years of age. Before taking or giving KYGEVVI, tell your healthcare provider about all of your medical conditions, including if you: have or have had liver problems are pregnant or plan to become pregnant. It is not known if KYGEVVI will harm your unborn baby. are breastfeeding or plan to breastfeed.

It is not known if KYGEVVI passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take KYGEVVI. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I take or give KYGEVVI? See the detailed Instructions for Use that comes with KYGEVVI for important information about the correct way to prepare and take or give a dose of KYGEVVI. Take or give KYGEVVI exactly as your healthcare provider tells you.

Your healthcare provider should tell you how much KYGEVVI to take or give, and when to take or give it. Your healthcare provider may change your or your child's dose of KYGEVVI depending on how you or your child respond to treatment and based on your or your child's weight. Take or give KYGEVVI 3 times a day about 6 hours apart.

Take or give KYGEVVI with food. KYGEVVI may be given through a feeding tube. KYGEVVI comes as a packet containing powder.

Prepare a one-day supply of KYGEVVI solution each morning. KYGEVVI should be prepared and given by adults only. Do not open the KYGEVVI packets until you are ready to use them.

Mix KYGEVVI powder only with room temperature water. Do not mix with any other liquids or foods. Only use the dosing cup, mixing bottle, and oral syringes provided with your ZX2000 administration kit.

Do not use a household measuring cup or measuring spoon. If you miss a dose of KYGEVVI, take the missed dose as soon as possible. If it is within 2 hours of your next scheduled dose, do not take the missed dose.

Take your next dose at your next scheduled time. Do not take 2 doses to make up for the missed dose. If you spit out the dose or do not take the full dose of KYGEVVI, do not take another dose.

Take your next dose at your next scheduled time. What are the possible side effects of KYGEVVI? KYGEVVI may cause serious side effects, including: Increased liver enzyme levels.

Increased liver enzyme levels in your blood are common with KYGEVVI. Your healthcare provider will do blood tests to check your liver enzyme levels before starting treatment and during treatment with KYGEVVI. Tell your healthcare provider right away if you develop any signs or symptoms of liver problems, including: loss of appetite pain on the right side of your stomach area dark or amber-colored urine yellowing of your skin or the white part of your eyes nausea and vomiting itching Stomach and intestinal (gastrointestinal) problems .

Diarrhea and vomiting are common with KYGEVVI, but may also be severe and lead to hospitalization. Tell your healthcare provider right away if you have diarrhea or vomiting during treatment with KYGEVVI that lasts longer than a few days. The most common side effects of KYGEVVI include: diarrhea stomach area (abdominal) pain including pain in the upper stomach area vomiting increased liver enzyme levels in your blood Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with KYGEVVI if you develop certain side effects.

These are not all of the possible side effects of KYGEVVI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store KYGEVVI? Store KYGEVVI packets at room temperature betwe… [Excerpted — this section continues on DailyMed.]

📖 Instructions for Use ~3 min read ▾

INSTRUCTIONS FOR USE KYGEVVI (KY-JEH-vee) (doxecitine and doxribtimine) powder, for oral solution Table of contents Instructions for use Important information Before you start Supplies for preparing and taking or giving KYGEVVI Important information What you need to know before preparing and taking or giving KYGEVVI Storing KYGEVVI packets and oral solution Preparing your one-day supply of KYGEVVI Get supplies ready Measure water and add powder from packets Mix and inspect medicine Dosing methods How to measure your individual dose Individual doses 50 mL or more Measure and take or give your individual dose Individual doses less than 50 mL Measure and take or give your individual dose Between individual doses Clean up after first and second individual dose End-of-day clean up Pour out and clean up after third individual dose Dosing cup maintenance Replacing the seal if misplaced or damaged Contact information Instructions For Use Important information This Instructions for Use contains information on how to prepare a one-day supply of KYGEVVI, and take or give an individual dose of KYGEVVI.

Read this Instructions for Use before taking or giving KYGEVVI and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your or your child's medical condition or treatment.

When you are prescribed KYGEVVI for the first time, you will be provided with the carton(s) of 30 KYGEVVI packets and the ZX2000 administration kit (see Figure A ). Only use the dosing cup, mixing bottle, and oral syringes provided with your ZX2000 administration kit. Do not use a household measuring cup or measuring spoon.

Figure A Before you start Supplies for preparing and taking or giving KYGEVVI Carton of 30 KYGEVVI packets Before you start Supplies for preparing and taking or giving KYGEVVI Important information What you need to know before preparing and taking or giving KYGEVVI You will prepare a one-day supply of KYGEVVI solution to be taken in 3 equal doses throughout the day (about 6 hours apart). KYGEVVI solution should be prepared on the same day as taking or giving your dose. KYGEVVI should be prepared and given by adults only.

Take or give KYGEVVI exactly as prescribed by your healthcare provider. Do not change your dose without talking with your healthcare provider. Do not take or give more than the prescribed amount of KYGEVVI solution.

Take KYGEVVI solution with food. Do not use KYGEVVI packets after the expiration date on the packet or carton. Only use the dosing cup, mixing bottle, and oral syringes provided with your ZX2000 administration kit.

Do not use a household measuring cup or measuring spoon. Each ZX2000 administration kit comes with two oral syringes. Keep the second oral syringe as a spare.

Rinse and dry the mixing bottle and dosing cup before first use. Do not use the dosing cup, mixing bottle, or oral syringe if it appears dirty or damaged. Each ZX2000 administration kit can be used for 6 months.

Contact your healthcare provider when you need a replacement. Contact your healthcare provider or pharmacist for a replacement if your mixing bottle, dosing cup, or oral syringe is damaged or if the markings are missing or no longer readable. Do not use the packets if the tamper evident seal on the carton is broken.

Mix KYGEVVI powder only with room temperature water. Do not mix KYGEVVI powder with any other liquids or foods. You may have KYGEVVI solution left over after taking or giving the 3 individual doses.

Throw away (discard) any remaining KYGEVVI solution 16 hours after preparing or after taking or giving the 3 doses, whichever comes first. If powder spills out of a packet before use, do not use the packet. Throw it away and use a new KYGEVVI packet.

If KYGEVVI solution comes in contact with your eyes or skin, rinse under cold water and contact your healthcare provider. KYGEVVI solution is compatible with most feeding tubes. Follow the steps in this In… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 74 words ▾

PRINCIPAL DISPLAY PANEL - 30 Packet Carton NDC 50474-350-30 Rx only kygevvi ® (doxecitine and doxribtimine) Powder for Oral Solution 2 g/2 g per packet Only use the dosing cup, mixing bottle, and oral syringes provided with your separate ZX2000 administration kit. See enclosed Instructions for Use for important preparation and administration instructions. 30 packets Each 4 g packet contains 2 g doxecitine and 2 g doxribtimine.

PRINCIPAL DISPLAY PANEL - 30 Packet Carton

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

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 — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“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 UCB, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
UCB, 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.
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.
← 50474-0002-63 · UCB, 50474-0370-66 · UCB, →
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.