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 walk, eat, and breathe independently, significantly impacting patient quality of life.2

Doxycitine and doxribtimine is a combined nucleoside therapy. The drug is aimed at supporting mitochondrial DNA replication and stabilizing mitochondrial function in patients. Through the incorporation of 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 adults and pediatric patients with symptom onset at ≤12 years of age.

In a statement, UCB wrote, “TK2d profoundly affects multiple health, physical, quality-of-life, and psychosocial domains, as children struggle to achieve developmental milestones or lose them, and adults lose functional independence with challenges in breathing, eating, and walking.”

On March 19, 2025, UCB presented the investigative therapy improved survival and functional outcomes, regulated safety, and positive impact on 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. A total of 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 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 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.