FDA Approves Kygevvi for Thymidine Kinase 2 Deficiency

The Food and Drug Administration (FDA) has approved Kygevvi^® for the treatment of thymidine kinase 2 deficiency in adults and pediatric patients with an age of symptom onset on or before 12 years. 

Thymidine kinase 2 deficiency (TK2d) is an ultra-rare genetic mitochondrial disease caused by mutations in the TK2 gene. This affects the body’s ability to produce and repair mitochondrial DNA, leading to symptoms such as muscle weakness and respiratory failure.

Kygevvi contains doxecitine and doxribtimine, both pyrimidine nucleosides. Following administration of Kygevvi, these pyrimidine nucleosides are incorporated into skeletal muscle mitochondrial DNA. This action is expected to restore mitochondrial DNA copy number in TK2d patients.

The approval was based on data from a phase 2 study (Trial 1: ClinicalTrials.gov Identifier: NCT03845712), 2 retrospective chart review studies (Study 1: ClinicalTrials.gov Identifier: NCT03701568; Study 2: ClinicalTrials.gov Identifier: NCT05017818), and an expanded access program. 

Across all studies, 82 patients with genetically confirmed TK2d with an age of symptom onset of less than or equal to 12 years were treated with Kygevvi or pyrimidine nucleosides. To measure the treatment’s efficacy, overall survival was compared between treated patients and untreated patients from an external control group. 

After matching 1:1 based on the age of when TK2d symptoms first appeared (≤2 years or >2 to ≤12 years), 78 pairs were identified and evaluated in the survival analysis (treated patients: Trial 1 [n=9], Study 1 [n=27], Study 2 [n=11], expanded access program [n=31]; untreated patients: published literature [n=57], Study 2 [n=21]). 

Among the 78 treated patients, the median age of TK2d symptom onset was 1.5 years (range: 0.01-12 years), the median duration of treatment was 4 years (range: 1 day to 12 years), and the median dose received was 762mg/kg/day (range: 260-800mg/kg/day). 

Findings showed Kygevvi reduced the overall risk of death by 86% compared with no treatment (hazard ratio, 0.14 [95% CI, 0.04-0.39]). There were 3 deaths in the Kygevvi treated arm vs 28 deaths in the matched untreated arm. 

Restricted mean survival times for treated patients vs matched untreated patients were also reported:

• Four years post treatment start: 3.8 (95% CI, 3.7-4) vs 2.6 years (95% CI, 2.20-3);
• Six years post treatment start: 5.8 (95% CI, 5.5-6) vs 3.7 years (95% CI, 3-4.3); and
• Ten years post treatment start: 9.6 (95% CI, 9.2-10) vs 5.7 years (95% CI, 4.5-6.9).

The most common adverse reactions with treatment were diarrhea, abdominal pain (including abdominal pain upper), vomiting, increased alanine aminotransferase (ALT), and increased aspartate aminotransferase (AST). Prior to initiating treatment, baseline AST, ALT, and total bilirubin should be obtained.

Kygevvi is supplied as single-use packets each containing 2g of doxecitine and 2g of doxribtimine (4g total). The recommended dosage is based on the patient’s weight. Following the preparation of Kygevvi with room temperature water, the mixed solution should be administered orally in 3 equally divided doses approximately 6 hours apart with food.

According to UCB, Kygevvi is expected to be commercially available in the US in the first quarter of 2026. 

This article originally appeared on MPR