Kygevvi Brings Hope for Patients With Rare Mitochondrial Disorder

On 3^rd November 2025, the U.S. Food and Drug Administration (FDA) has approved Kygevvi as the first and only treatment for thymidine kinase 2 deficiency (TK2d). Kygevvi, a combination of doxecitine and doxribtimine, was granted Breakthrough Therapy, Orphan Drug, Priority Review, and Rare Pediatric Disease designations by the FDA, recognizing the urgent, need for an effective intervention for this devastating disorder. The marketing authorization holder for Kygevvi (doxecitine and doxribtimine) is UCB, a global biopharmaceutical company headquartered in Belgium. This approval marks a groundbreaking advancement for both adults and pediatric patients living with this rare, life-threatening mitochondrial disease characterized by progressive muscle weakness and respiratory failure.

About Thymidine Kinase 2 Deficiency

Thymidine Kinase 2 Deficiency (TK2d) is a rare, inherited mitochondrial disorder caused by mutations in the TK2 gene. This gene encodes the enzyme thymidine kinase 2, which is crucial for the production and maintenance of mitochondrial DNA (mtDNA) by recycling nucleotides needed for mtDNA replication and repair. Mutations in the TK2 gene lead to a deficiency or dysfunction of this enzyme, resulting in progressive depletion or deletions in mtDNA, which impairs the mitochondria’s ability to produce energy. This leads to progressive muscle weakness, respiratory difficulties, and other systemic symptoms predominantly affecting skeletal muscles, and in late-onset forms, symptoms like ptosis (drooping eyelids), ophthalmoparesis (eye muscle weakness), and motor difficulties.

About Kygevvi

During development, the FDA granted Kygevvi Orphan Drug, Breakthrough Therapy, Priority Review, and Rare Pediatric Disease designations, and upon approval awarded UCB a Rare Pediatric Disease Priority Review Voucher, reflecting significant need and facilitating expedited review timelines. Invented and developed by UCB, Kygevvi is the first and only approved therapy for thymidine kinase 2 deficiencies, establishing a new standard of care for both pediatric and adult patients with symptom onset on or before 12 years and shifting management from purely supportive care to disease‑modifying treatment targeting the root mitochondrial defect.

Kygevvi contains two pyrimidine nucleosides, doxecitine and doxribtimine, which work by replenishing mitochondrial DNA in skeletal muscle. This combination supports mitochondrial DNA replication by bypassing the deficient TK2 enzyme and utilizing cytosolic kinases. This restoration helps cells produce energy efficiently, counteracting the molecular deficit caused by TK2d mutations.