UCB Wins First FDA Approval for Ultra-Rare Mitochondrial Disease: Kygevvi for Thymidine Kinase 2 Deficiency (TK2d)

The FDA has approved Kygevvi (doxecitine and doxribtimine) as the first and only treatment for thymidine kinase 2 deficiency (TK2d), an ultra-rare and life-threatening genetic mitochondrial disease characterized by progressive muscle weakness1 2 4 5 9 11 13 14 15.

TK2d often leads to severe disability and fatality within three years of early symptom onset, typically occurring at or before age 124 5 14.

Kygevvi is indicated for adults and pediatric patients with symptom onset at or before 12 years old, addressing an unmet medical need as patients previously only had access to supportive or palliative care1 2 5 14.

The combination therapy, comprising two pyrimidine nucleosides—doxecitine and doxribtimine—restores mitochondrial DNA copy number in TK2d by incorporating deoxycytidine and deoxythymidine into skeletal muscle mitochondrial DNA1 5 14.

Clinical evidence supporting approval came from a Phase II clinical trial, two retrospective chart reviews, and an expanded access program involving 82 patients. The therapy significantly reduced overall risk of death by about 86% compared to untreated patients1 4 14.

Kygevvi received multiple FDA designations:
Orphan Drug, Breakthrough Therapy, Priority Review, and Rare Pediatric Disease, and UCB was awarded a Rare Pediatric Disease Priority Review Voucher1 5.

Kygevvi has only been approved for use in the United States with commercial availability anticipated in the first quarter of 20261.

This approval marks a major step forward for the rare disease and mitochondrial disease communities, offering hope and the first targeted therapeutic option for affected families and clinicians2 3 5.