Kygevvi (doxecitine and doxribtimine)
An approved treatment for Thymidine Kinase 2 Deficiency.
The same compound appears under different names depending on the context. Here is how to identify Doxecitine and doxribtimine wherever you encounter it, plus the key facts at a glance.
- Generic name
- Doxecitine and doxribtimine
- Brand name
- Kygevvi
- Development code
- MT1621
- Drug class
- Pyrimidine nucleoside (oral combination)
- Manufacturer
- UCB
- How it's taken
- Kygevvi is supplied as 2g/2g powder packets (2 grams of each ingredient per packet) for oral solution.
The first FDA-approved therapy for thymidine kinase 2 deficiency (TK2d), an ultra-rare mitochondrial muscle disease. Kygevvi is an oral powder containing two pyrimidine nucleosides (doxecitine and doxribtimine) that act as substitute building blocks for mitochondrial DNA. Approved on November 3, 2025 for adults and pediatric patients whose TK2d symptoms began on or before age 12.
Where Doxecitine and doxribtimine fits
First and only FDA-approved therapy specifically for thymidine kinase 2 deficiency (approved November 3, 2025, and still the only one as of September 2026) and the first treatment ever approved for any mitochondrial DNA depletion syndrome. The on-label indication covers adults and pediatric patients whose symptoms began on or before age 12. Standard supportive care continues alongside Kygevvi: respiratory support (BiPAP, ventilator) when needed, swallowing therapy and feeding support, physical and occupational therapy, and proactive monitoring of pulmonary function.
How Doxecitine and doxribtimine works
TK2d patients have a defective enzyme called thymidine kinase 2 inside their muscle mitochondria. The job of TK2 is to phosphorylate (turn on) two key building blocks — deoxycytidine and deoxythymidine — so mitochondria can use them to copy and repair their own DNA. When TK2 is broken, mitochondrial DNA cannot be maintained and muscle cells gradually run out of energy.
Kygevvi is an oral powder mixed with water that contains doxecitine (a deoxycytidine analog) and doxribtimine (a deoxythymidine analog). Once absorbed, these molecules bypass the broken TK2 step and feed the building blocks directly into the mtDNA-making process inside skeletal muscle mitochondria. In animal models the drug restored normal mtDNA copy number; in patients it has reduced the overall risk of death by approximately 86% and helped many patients regain motor milestones they had lost.
Mechanism: Pyrimidine nucleoside replacement therapy. Provides the deoxycytidine and deoxythymidine building blocks that mitochondria need to copy and repair their own DNA, bypassing the defective TK2 enzyme step in skeletal muscle.
Side effects and safety
The most common side effects (occurring in 5% or more of patients) are diarrhea, abdominal pain, vomiting, and elevated liver enzymes (alanine aminotransferase / ALT and aspartate aminotransferase / AST). Liver function blood tests are required before starting and periodically during treatment. Some side effects are more pronounced when treatment is first started or when the dose is increased. Diarrhea and vomiting can be severe: some patients needed a hospital stay, a lower dose, or to stop treatment, so tell the care team if these happen or do not go away.
This is not a complete list of side effects. Talk to your doctor or pharmacist about what to expect and when to seek medical attention.
Taking Doxecitine and doxribtimine
Kygevvi is supplied as 2g/2g powder packets (2 grams of each ingredient per packet) for oral solution. The powder is mixed with water once a day to make a 1-day supply, then taken by mouth (or by feeding tube) in 3 equal doses about 6 hours apart, with food. Dosing is based on body weight for all patients, adults and children, and is increased in steps up to 800 mg/kg/day as tolerated. Kygevvi has been commercially available in the U.S. since March 2026.
Availability and cost
Only available as the brand-name product.
Targeted therapy for an ultra-rare disease (worldwide prevalence of about 1.64 per 1,000,000). Coverage typically requires biochemical or genetic confirmation of TK2d. UCB operates a patient services program for U.S. patients.
Help paying for Kygevvi
Pick your insurance to see which help fits. Drugmaker copay cards can't be used with Medicare, Medicaid or TRICARE; charity funds are the usual route there.
- Insurance and case manager help
Dedicated Care Coordinator reviews insurance and financial assistance options, even if uninsured, and works with specialty pharmacy PANTHERx Rare.
For: no insurance · source
Good to know: Official pages mention financial assistance options but name no specific copay or free-drug program for Kygevvi.
Clinical trial results
FDA approval was based on a multi-study clinical program rather than a single Phase 3 trial, because TK2d is so rare that running a placebo-controlled trial was not feasible. Evidence came from a Phase 2 open-label study (NCT03845712), 2 retrospective chart review studies (NCT03701568 and NCT05017818), and an expanded access program. Survival in treated patients was compared with a matched group of untreated patients from published reports and one of the chart reviews. Treatment reduced the overall risk of death by approximately 86% (95% CI: 61%, 96%) compared with untreated natural history controls. 75% of treated patients regained at least one motor milestone they had previously lost. 16% of patients on ventilatory support were able to reduce or discontinue it.
Development history
The deoxynucleoside therapy concept for TK2d was pioneered by Dr. Michio Hirano and colleagues at Columbia University in the early 2010s, originally as a compassionate-use program. The clinical program was acquired by Modis Therapeutics and then by Zogenix in 2020, with the development code MT1621. UCB acquired Zogenix in 2022 to add this and other rare disease assets to its portfolio. The FDA granted approval on November 3, 2025, making Kygevvi the first targeted therapy for any of the mitochondrial DNA depletion syndromes.
Explore Thymidine Kinase 2 Deficiency trials
Common questions about Doxecitine and doxribtimine
▸What is Doxecitine and doxribtimine (Kygevvi)?
The first FDA-approved therapy for thymidine kinase 2 deficiency (TK2d), an ultra-rare mitochondrial muscle disease. Kygevvi is an oral powder containing two pyrimidine nucleosides (doxecitine and doxribtimine) that act as substitute building blocks for mitochondrial DNA. Approved on November 3, 2025 for adults and pediatric patients whose TK2d symptoms began on or before age 12.
▸How does Doxecitine and doxribtimine work?
TK2d patients have a defective enzyme called thymidine kinase 2 inside their muscle mitochondria. The job of TK2 is to phosphorylate (turn on) two key building blocks — deoxycytidine and deoxythymidine — so mitochondria can use them to copy and repair their own DNA. When TK2 is broken, mitochondrial DNA cannot be maintained and muscle cells gradually run out of energy.
Kygevvi is an oral powder mixed with water that contains doxecitine (a deoxycytidine analog) and doxribtimine (a deoxythymidine analog). Once absorbed, these molecules bypass the broken TK2 step and feed the building blocks directly into the mtDNA-making process inside skeletal muscle mitochondria. In animal models the drug restored normal mtDNA copy number; in patients it has reduced the overall risk of death by approximately 86% and helped many patients regain motor milestones they had lost.
▸What are the side effects of Doxecitine and doxribtimine?
The most common side effects (occurring in 5% or more of patients) are diarrhea, abdominal pain, vomiting, and elevated liver enzymes (alanine aminotransferase / ALT and aspartate aminotransferase / AST). Liver function blood tests are required before starting and periodically during treatment. Some side effects are more pronounced when treatment is first started or when the dose is increased. Diarrhea and vomiting can be severe: some patients needed a hospital stay, a lower dose, or to stop treatment, so tell the care team if these happen or do not go away.
▸How is Doxecitine and doxribtimine taken?
Kygevvi is supplied as 2g/2g powder packets (2 grams of each ingredient per packet) for oral solution. The powder is mixed with water once a day to make a 1-day supply, then taken by mouth (or by feeding tube) in 3 equal doses about 6 hours apart, with food. Dosing is based on body weight for all patients, adults and children, and is increased in steps up to 800 mg/kg/day as tolerated. Kygevvi has been commercially available in the U.S. since March 2026.
▸Is Doxecitine and doxribtimine FDA approved?
Yes, Doxecitine and doxribtimine (Kygevvi) is FDA approved (2025) for the treatment of Thymidine Kinase 2 Deficiency.
▸Is Kygevvi the first FDA-approved treatment for TK2d?
Yes. On November 3, 2025, the FDA approved Kygevvi (doxecitine and doxribtimine) as the first and only treatment specifically for thymidine kinase 2 deficiency in adults and pediatric patients whose symptoms began on or before age 12. Kygevvi has been commercially available in the U.S. since March 2026.
▸How does Kygevvi work?
TK2d patients have a broken enzyme called thymidine kinase 2 that normally helps mitochondria make and repair their own DNA. Kygevvi is an oral powder containing two pyrimidine nucleosides (deoxycytidine and deoxythymidine analogs) that bypass the broken enzyme and provide the building blocks mitochondria need directly. It does not correct the underlying TK2 gene mutation, so it must be taken long-term.
▸What does the trial evidence show?
Across UCB's combined clinical program, Kygevvi reduced the overall risk of death by approximately 86 percent compared with untreated patients in a natural-history comparison. 75 percent of treated patients regained at least one motor milestone they had previously lost (such as sitting, standing, or walking), and 16 percent of patients on ventilatory support were able to reduce or stop it. Earlier treatment was associated with greater benefit.
▸What are the most common side effects?
The most common side effects (occurring in 5 percent or more of patients) are diarrhea, abdominal pain, vomiting, and elevated liver enzymes (ALT and AST — the standard liver-function blood tests). Liver enzyme monitoring is required before starting Kygevvi and periodically during treatment. Side effects tend to be more pronounced when starting therapy or increasing the dose.
▸Should asymptomatic siblings of a TK2d patient be tested?
Yes — discuss with a genetic counselor or metabolic specialist. TK2d is autosomal recessive, so each sibling has a 25 percent chance of being affected. Because earlier treatment with Kygevvi is associated with greater benefit, identifying an affected sibling before significant muscle damage occurs can change their lifetime trajectory.
Sources and references
Every factual claim on this page is drawn from the public sources listed below. Click any reference to open the original document.
- UCB · November 3, 2025. U.S. FDA approves KYGEVVI (doxecitine and doxribtimine), the first and only treatment for adults and children living with thymidine kinase 2 deficiency (TK2d). https://www.ucb.com/newsroom/press-releases/article/us-fda-approves-kygevvitm-doxecitine-and-doxribtimine-the-first-and-only-treatment-for-adults-and-children-living-with-thymidine-kinase-2-deficiency-tk2d
- Muscular Dystrophy Association · November 3, 2025. FDA Approves KYGEVVI, the First and Only Treatment for Adults and Children Living with TK2d. https://www.mda.org/press-releases/fda-approves-kygevvi-the-first-and-only-treatment-for-Thymidine-Kinase-2-deficiency
- United Mitochondrial Disease Foundation. TK2d. https://umdf.org/tk2d/
- NCBI Bookshelf / GeneReviews. TK2-Related Mitochondrial DNA Maintenance Defect, Myopathic Form. https://www.ncbi.nlm.nih.gov/books/NBK114628/
- ClinicalTrials.gov. Treatment of TK2 Deficiency With Thymidine and Deoxycytidine (NCT03639701). https://clinicaltrials.gov/study/NCT03639701