The U.S. Food and Drug Administration (FDA) has approved Kygevvi for the treatment of adults and pediatric patients, with an age of symptom onset on or before 12 years, with thymidine kinase 2 deficiency (TK2d).
TK2d is a rare genetic disease characterized by progressive and severe muscle weakness. It is often fatal, with those experiencing initial symptoms on or before the age of 12 years facing a high risk of premature death (often occurring within 3 years after symptom onset). Other common symptoms include breathing difficulties, weakness in the eye muscles, and trouble chewing and swallowing. TK2d is caused by genetic mutations in the TK2 gene.
Kygevvi is a combination of two pyrimidine nucleosides, doxecitine and doxribtimine, that target and restore mitochondrial DNA in the skeletal muscle. It is the first and only treatment approved for patients with TK2d. The approval is based on safety and efficacy data from a phase 2 clinical trial, two retrospective chart review studies, and an expanded access use program.
A total of 82 unique patients were involved in these studies. Efficacy was assessed by comparing overall survival in these pediatric and adult treated patients to an external control group of untreated patients who were matched to treated patients using age of TK2d symptom onset. A total of 78 matched pairs were identified.
Results indicated that survival trim from treatment start improved and that treatment reduced the overall risk of death from treatment start by about 86%. Of the 78 treated patients, the median age of symptom onset was 1.5 years. The median duration of treatment was 4 years and the median dose received was 762 mg/kg/day.
The most common adverse reactions were diarrhea, abdominal pain, vomiting, increased alanine aminotransferase, and increased aspartate aminotransferase.
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To learn more about TK2d and other rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/