First Thymidine Kinase 2 Deficiency Treatment Receives FDA Nod

The Food and Drug Administration (FDA) has approved Kygevvi (doxecitine and doxribtimine; UCB, Brussels, Belgium) for the treatment of adult and pediatric patients with thymidine kinase 2 deficiency (TK2d) with an age of symptom onset at or before 12 years. Kygevvi is the first and only therapy approved for the treatment of people with TK2d, an ultra-rare, life-threatening mitochondrial disorder caused by mutations in the TK2 gene associated with progressive muscle weakness and early mortality. According to a statement released by UCB, before the approval of Kygevvi, management for people with TK2d was limited to supportive care.

The FDA’s decision was supported by data from a Phase 2 clinical trial (NCT03845712), 2 retrospective chart reviews (NCT03701568; NCT05017818), and an Expanded Access Program (NCT06590493), which cumulatively included 82 individuals with TK2d and an age at symptom onset of  ≤12 years. Researchers measured the efficacy of the medication based on a comparison of overall survival in Kygevvi-treated participants vs an external control group, with 78 matched pairs in total.

Key findings included the following:

• Treatment with Kygevvi reduced the risk of death by approximately 86% compared with matched untreated controls (95% CI, 61% to 96%).
• Participants received a median of 4 years of Kygevvi treatment (range, 1 day to 12 years), with a median dose of 762 mg/kg/d (range, 260 mg/kg/d to 800 mg/kg/d).
• Common adverse events included diarrhea, abdominal pain, vomiting, and elevations in liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]).

According to UCB’s announcement, Kygevvi—a combination of 2 pyrimidine nucleosides—functions by restoring mitochondrial DNA replication in skeletal muscle cells. The therapy received Orphan Drug, Breakthrough Therapy, Priority Review, and Rare Pediatric Disease designations from the FDA. UCB expects Kygevvi to be available in the United States in the first quarter of 2026 and has announced plans for personalized support programs to increase access.

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