Kygevvi Approved for Thymidine Kinase 2 Deficiency

On Nov. 3, 2025, the US Food and Drug Administration (FDA) approved UCB’s Kygevvi^® (doxecitine and doxribtimine) for the treatment of thymidine kinase 2 deficiency (TK2d) in adults and children whose symptoms started when they were 12 years of age or younger. TK2d is an ultra-rare genetic disorder that impairs the body’s ability to produce and repair mitochondrial DNA (mtDNA), resulting in impaired energy production, progressive muscle weakness and respiratory failure. Kygevvi, a pyrimidine nucleoside replacement therapy, restores mitochondrial DNA synthesis in patients who have TK2d. The recommended dose is a weight-based, reconstituted oral solution that is taken in three equally divided doses, approximately six hours apart (plus or minus two hours), with food. It will be available in the first quarter of 2026. Full prescribing information can be found here.

At a Glance

• Brand Drug: Kygevvi^® (doxecitine and doxribtimine)
• Manufacturer: UCB
• Date Approved: Nov. 3, 2025
• Indication: 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
• Dosage Forms Available: 2g doxecitine and 2g doxribtimine powder for oral solution
• Launch Date: First quarter of 2026
• Estimated Annual Cost: Unknown
• FDA Designation: Orphan Drug. Breakthrough Therapy. Rare Pediatric Disease. Priority Review.
• TK2d is an ultra-rare inherited disorder that impairs mitochondrial DNA production and repair, leading to progressive muscle weakness, respiratory failure and is often fatal. There are only about 120 cases reported in the medical literature, though it is likely underdiagnosed.
• Approval was based on phase II data, two retrospective chart review studies and an expanded access program showing significant improvement in survival in TK2d patients with symptom onset at age 12 years or younger treated with Kygevvi, reducing mortality from 36% to 4% compared to untreated patients. It also extended the mean survival at 10 years from 5.7 to 9.6 years. Phase II data also showed 92–95% reduction in mortality risk and significant improvement in motor milestones.
• The most common side effects include diarrhea, vomiting, elevated liver enzymes and abdominal pain.
• Kygevvi is the first approved treatment for TK2d. Prior standard care was supportive only, including respiratory care, nutritional support and physical therapy.
• Implications: Express Scripts is investigating data on Kygevvi for a possible utilization management strategy. It will be excluded at launch on the Express Scripts National Preferred Formulary (NPF) until our formulary development process is complete.