FDA Approves Kygevvi, First Treatment for Thymidine Kinase 2 Deficiency

The US Food and Drug Administration (FDA) has approved UCB’s doxycitine and doxribtimine (Kygevvi), the first therapy for thymidine kinase 2 deficiency (TK2d), an ultra-rare, inherited mitochondrial disease.1

With only 120 reported cases (1.64 per 1,000,000 people), TK2d had no previously approved therapy. The mitochondrial depletion syndrome impairs the body’s ability to produce and repair mitochondrial DNA. Without intervention, the disease impacts an individual’s ability to function independently, and is often fatal within 3 years of symptom onset.2,3

"I've been studying mitochondrial diseases for more than three decades and have witnessed firsthand the impact TK2d has on patients and their families,” said Michio Hirano, MD at Columbia University Irving Medical Center. “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."

Doxycitine and doxribtimine is a combined nucleoside therapy given to patients for 4 years at a range of 260 to 800 mg/kg/day. The drug supports mitochondrial DNA replication and stabilizes mitochondrial function in patients. By incorporating the nucleosides deoxycytidine and deoxythymidine into skeletal muscle mitochondrial deoxyribonucleic acid, individuals can restore DNA copy and improve skeletal muscle function.

The November 3, 2025, approval was supported by data from a phase 2 clinical study, 2 retrospective reviews, and an expanded access program, including 82 adult and pediatric patients with symptom onset at ≤12 years of age.

"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."

On March 19, 2025, UCB presented the investigative therapy, which improved survival and functional outcomes, regulated safety, and positively impacted the quality of life for individuals and caregivers, at the Muscular Dystrophy Association 2025 Conference. The application was granted a priority review, Breakthrough Therapy Designation, and Rare Pediatric Disease Designation.

In a matched survival analysis of 78 pairs of treated and untreated patients, mortality was significantly lower in the doxecitine and doxribtime group. 3 deaths occurred in the patient population receiving doxecitine and doxribtime (4%), and there were 28 deaths in the control group (36%). During a 10-year follow-up, patients in the Kygevvie group’s mean survival was 9.6 years compared to 5.7 years in the control group.

Patients with TK2d ≤12 years of age saw further improvement in their clinical outcomes and quality of life. In the time from symptom onset to starting Kygevvie treatment, the risk of death reduced from 92–94% (hazard ratio [HR], 0.06–0.08; P <.0001) to 87–95% (HR, 0.05–0.13; P <.0001). Of the included patients 75% (30/40) regained ≥1 lost motor milestone, and 22.5% (9/40) regained ≥4 motor milestones.

References

1. Center. FDA approves 1st drug for thymidine kinase 2 deficiency. U.S. Food and Drug Administration. Published 2025. Accessed November 3, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-1st-drug-thymidine-kinase-2-deficiency-very-rare-mitochondrial-disease.

2. New data on investigational therapy for thymidine kinase 2 deficiency presented at Muscular Dystrophy Association (MDA) 2025 Conference | UCB. Ucb-usa.com. Published March 19, 2025. Accessed November 3, 2025. https://www.ucb-usa.com/stories-media/UCB-U-S-News/detail/article/new-data-on-investigational-therapy-for-thymidine-kinase-2-deficiency-presented-at-muscular-dystrophy-association-mda-2025-conference.

3. UCB. U.S. FDA approves KYGEVVI® (doxecitine and doxribtimine), the first and only treatment for adults and children living with thymidine kinase 2 deficiency (TK2d). Prnewswire.com. Published November 3, 2025. Accessed November 4, 2025. https://www.prnewswire.com/news-releases/us-fda-approves-kygevvi-doxecitine-and-doxribtimine-the-first-and-only-treatment-for-adults-and-children-living-with-thymidine-kinase-2-deficiency-tk2d-302603083.html.