The US Food and Drug Administration has approved Kygevvi (doxecitine and doxribtimine) powder for the treatment of thymidine kinase 2 deficiency in patients with symptom onset at age 12 years or younger. The approval marks the first available therapy for this ultra-rare mitochondrial disease and includes Breakthrough Therapy Designation.

Thymidine kinase 2 deficiency (TK2d) is an inherited genetic disorder that impairs mitochondrial DNA (mtDNA) production and repair, classified as a mitochondrial depletion syndrome. Clinical manifestations include progressive muscle weakness and respiratory failure. Approximately 120 cases have been documented in medical literature, though the true prevalence may be higher due to underdiagnosis.

The approval was based on efficacy data from multiple sources: one phase 2 clinical trial, two retrospective chart reviews, and an expanded access program. Investigators conducted survival analysis comparing 78 matched pairs of treated vs untreated patients, with the control group derived from published literature and retrospective data.

Results demonstrated 3 deaths (4%) among Kygevvi-treated patients compared with 28 deaths (36%) in the untreated control group. Mean survival time at 10 years was 9.6 years for treated patients compared with 5.7 years for controls.

The most frequently reported adverse events included diarrhea, vomiting, elevated liver enzymes, and abdominal pain.

The drug is indicated for adults and pediatric patients with early-onset TK2d.

Source: FDA