On 31 March 2026, the European Commission granted a marketing authorisation (MA) under exceptional circumstances for Kygevvi (doxecitine and doxribtimine) for the treatment of mitochondrial myopathies with thymidine kinase 2 (TK2) deficiency, following the favourable opinion issued by the CHMP (EMA) in January 2026. On 21 May 2026, the HAS granted early access authorisation following marketing authorisation, enabling the treatment costs to be covered for affected patients. The marketing authorisation applies only to patients whose symptoms began before the age of 12, as data remain limited for cases where the disease manifests later in life.
- A prospective study, conducted on eleven adults whose first symptoms appeared around the age of 27 and who were followed up for two years, provides information on the natural history and prognosis of these late-onset forms.
- Patients exhibited a decline in motor and respiratory function, notably including a worsening of the 100-metre walk test (+6 seconds) and a reduction in forced vital capacity (-9.11 per cent).
- The prognosis varied according to phenotype, with a more severe clinical course observed particularly 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 scans revealed involvement of several muscles, notably the gluteus maximus, where the proportion of adipose tissue correlated with the degree of motor impairment.
All patients experienced a significant impact on their quality of life, highlighting the urgent need to assess the potential benefits of nucleoside therapy in late-stage forms of the disease as well.
Another Turkish study reports the long-term results (follow-up of up to three years) of nucleoside therapy (doxecitine and doxribtimine) in six adults with late-onset TK2 deficiency, treated under a compassionate use programme. The results show:
- Good tolerance of the treatment.
- Sustained motor and respiratory improvements: walking distance tripled on average (up to fourfold in patients followed for three years), an improvement in the HFMSE of more than 8 points at six months (up to +37 in patients followed for three years), and stabilisation or improvement in FVC in all patients (an average increase of 20 points after three years, compared with a decline prior to treatment).
- A reduction of approximately 30% in fatigue and an improvement in BMI in underweight patients.
The benefit is all the more pronounced when treatment is started early, but partial improvements remain possible even in advanced stages.
These results will need to be confirmed in a larger cohort, but suggest that the benefit of nucleoside therapy is not limited to early forms of the disease.
First treatment for rare thymidine kinase 2 deficiency. European Medicines Agency (EMA). 30 January 2026 press release.
KYGEVVI (doxécitine et doxribtimine) — Déficit en thymidine kinase 2 (TK2d) : autorisation d’accès précoce. Haute Autorité de santé. 21 mai 2026.
