U.S. FDA approves KYGEVVI® (doxecitine and doxribtimine), the first and only treatment for adults and children living with thymidine kinase 2 deficiency (TK2d)

• Approved indication: KYGEVVI^® (doxecitine and doxribtimine) powder for oral solution (2g/2g) is approved 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
• Survival benefit: Treatment reduced the overall risk of death from the start of treatment by approximately 86% (95% CI: 61%, 96%).¹
• Burden of disease: TK2d is an ultra-rare, life-threatening, genetic mitochondrial disease characterized by progressive and severe muscle weakness (myopathy).²

ATLANTA, Nov. 3, 2025 /PRNewswire/ -- UCB (Euronext Brussels: UCB), a global biopharmaceutical company, today announced that KYGEVVI^® has been granted approval by the U.S. Food and Drug Administration (FDA) for the treatment of adults and pediatric patients living with thymidine kinase 2 deficiency (TK2d), with an age of symptom onset on or before 12 years.¹ It is the first and only approved treatment for these patients living with TK2d.

TK2d is an ultra-rare, life-threatening, genetic mitochondrial disease characterized by progressive (worsening over time) and severe muscle weakness (myopathy) with no approved treatment options beyond supportive care until now.^2,3,4,5 It is often fatal, with those experiencing initial symptoms on or before the age of 12 years facing a high risk of premature death (often occurring within 3 years after symptom onset).⁶ It is estimated that the worldwide prevalence of TK2d is 1.64 [0.5, 3.1] cases per 1,000,000 people.⁷

"The approval of doxecitine and doxribtimine represents a pivotal moment for the TK2d community who previously had no FDA-approved treatment options for this rare genetic mitochondrial disease beyond supportive [palliative] care," said Donatello Crocetta, Chief Medical Officer at UCB. "We extend heartfelt thanks to the patients, families and friends, advocates, healthcare providers and dedicated clinical trial teams who have partnered with us on this important journey."

"It's hard to overstate the importance of this FDA approval for those diagnosed with TK2d. This is an ultra-rare disease community in dire need of treatment options. For too long, caregivers and their families have had to endure the burden of this disease," said Kristen Clifford, United Mitochondrial Disease Foundation President and CEO. "Having the first-ever FDA-approved therapy for TK2d in this patient population not only meets a critical medical need - it represents something greater - hope for the future."

"I've been studying mitochondrial diseases for more than three decades and have witnessed firsthand the impact TK2d has on patients and their families. We have been waiting for an approved treatment for many years, and this approval marks a significant milestone in how we can support and manage this debilitating condition," said Dr. Michio Hirano, Professor of Neurology and Chief of the Division of Neuromuscular Medicine at Columbia University Irving Medical Center.

Supporting data
The KYGEVVI approval is supported by safety and efficacy data from one Phase 2 clinical study, two retrospective chart review studies, and an expanded access use program*.^1,8,9,10,11 These studies included a total of 82 unique patients treated with KYGEVVI or pyrimidine nucleosides with an age of TK2d symptom onset ≤12 years. Efficacy was assessed by comparing overall survival in these pediatric and adult treated patients to an external control group of untreated patients who were matched to treated patients using age of TK2d symptom onset (≤ 2 years or >2 to ≤ 12 years).¹ A total of 78 matched pairs were identified. The results showed that survival time from treatment start was improved; treatment reduced the overall risk of death from treatment start by approximately 86% (95% CI: 61%, 96%).¹ Of the 78 treated patients included in the survival analysis, the median age of TK2d symptom onset was 1.5 years (range: 0.01 to 12 years).¹ 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).¹

The most common adverse reactions (incidence ≥5%) are diarrhea, abdominal pain (including abdominal pain upper), vomiting, alanine aminotransferase increased (ALT), and aspartate aminotransferase increased (AST).¹

A regulatory review of doxecitine and doxribtimine is currently underway by the EMA (European Medicines Agency), and further regulatory submissions are planned. KYGEVVI is currently not approved for use in any indication by any regulatory authority outside of the U.S. UCB expects KYGEVVI to be commercially available in the U.S. in Q1, 2026. To further its mission of equitable care, UCB will provide a personalized support program for KYGEVVI that places the needs of patients and caregivers at the forefront.

In the U.S., KYGEVVI received Orphan Drug, Breakthrough, Priority Review and Rare Pediatric Disease designations from the FDA.^12,13 With this approval by FDA, UCB was awarded a Rare Pediatric Disease Priority Review Voucher (RPDPRV) redeemable for a priority review for a future marketing application.

About KYGEVVI
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 Administration of KYGEVVI is intended to incorporate the pyrimidine nucleosides, deoxycytidine and deoxythymidine, into skeletal muscle mitochondrial DNA.1 This action restores mitochondrial DNA copy number in TK2d mutant mice.¹ 

Important safety information for KYGEVVI¹

Increase in Liver Transaminases

Elevated liver transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels were reported in patients treated with KYGEVVI. 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.

Gastrointestinal Adverse Reactions

Diarrhea and vomiting leading to hospitalization, dose reduction, and permanent discontinuation were reported in patients treated with KYGEVVI. 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.

Please see the full U.S Prescribing Information for additional information. Talk to your healthcare provider about your condition or your treatment.

*The KYGEVVI^® approval is supported by safety and efficacy data from one Phase 2 clinical study (Trial 1, (NCT03845712), two retrospective chart review studies (Study 1 and Study 2, NCT03701568 and NCT05017818 respectively), and an expanded access use program (NCT06590493).

For more information about the trial visit: https://clinicaltrials.gov/study/NCT03845712 (NCT03845712); https://clinicaltrials.gov/study/NCT03701568 (NCT03701568); https://clinicaltrials.gov/study/NCT05017818 (NCT05017818); https://clinicaltrials.gov/study/NCT06590493 (NCT06590493).

For further information, contact UCB: 

Global Communications
Nick Francis
T: +44 7769 307745
nick.francis@ucb.com

US Rare Diseases Communications
Daphne Teo
T: +1 770.880.7655
daphne.teo@ucb.com

Corporate Communications, Media Relations
Laurent Schots 
T +32.2.559.92.64 
laurent.schots@ucb.com

Investor Relations
Antje Witte 
T +32.2.559.94.14 
antje.witte@ucb.com

About UCB
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 9 000 people in approximately 40 countries, the company generated revenue of € 6.1 billion in 2024. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news

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References:

KYGEVVI^® is a registered trademark of the UCB Group of Companies.
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