In January 2026, the European Medicines Agency (EMA) issued a favourable opinion on granting marketing authorisation (MA) for Kygevvi (doxecitine and doxribtimine) for the treatment of mitochondrial myopathies with thymidine kinase 2 (TK2) deficiency. This opinion only applies to patients whose symptoms began before the age of 12, as data remains limited when the disease appears later in life.
A prospective study of eleven adults whose first symptoms appeared around the age of 27 provides a better understanding of the natural history and prognosis of these late-onset forms.
- During the two-year follow-up, patients experienced a decline in motor and respiratory function, including a worsening of the 100-metre walk test (+6 seconds) and a decrease in forced vital capacity (-9.11%).
- The prognosis varied according to phenotype, with a more severe clinical course mainly observed in those whose symptoms began in adolescence or early adulthood.
- Serum GDF15 levels were elevated and significantly correlated with motor and respiratory function, confirming its usefulness as a biomarker in clinical trials.
- MRI showed involvement of several muscles, particularly the gluteus maximus, whose fat fraction correlated with motor deficit.
All patients experienced a significant impact on their quality of life, highlighting the urgent need to evaluate the potential benefits of nucleoside therapy in late-onset forms as well.
