Caterina Garone, PhD, MD, Associate Professor at the University of Bologna, discusses safety and efficacy data on Kygevvi (doxecitine and doxribtimine) in patients with thymidine kinase 2 deficiency (TK2d).
TK2d is a rare genetic disease characterized by progressive and severe muscle weakness. It is often fatal. Patients who develop symptoms before the age of 12 years tend to show rapid disease progression and are at high risk of premature death. 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 by the U.S. Food and Drug Administration (FDA) in November 2025, for patients with TK2d.
New data published in Brain Communications examines the safety and efficacy of Kygevvi in TK2d and highlights the progressive disease burden in untreated patients.
Safety and efficacy data were pooled from retrospective (NCT03701568, NCT05017818) and prospective (NCT03845712) studies and expanded access programs of patients treated with Kygevvi. Untreated patients were pooled from literature reviews and a retrospective chart review study (NCT05017818).
A total of 218 patients were included (104 treated; 114 untreated) and most patients had an age of symptom onset at or before 12 years. In the age-of-symptom-onset-12-years-or-earlier subgroup, restricted mean survival time was 29.2 years over the 30 years after symptom onset for treated patients and 14.4 years for untreated patients.
Loss of 1 or more acquired motor milestones was more frequent before treatment start than after. Substantially more patients regained 1 or more lost motor milestone after treatment start than before. Ventilatory and feeding support were used across all age-of-symptom-onset subgroups, but some patients reduced or discontinued support after starting treatment and fewer patients initiated support after treatment start than before.
Most treatment-emergent adverse events (AEs) did not lead to discontinuation. The most frequent AE was diarrhoea, which was generally mild or moderate and resolved with dose reduction. Serious AEs occurred in 56% of patients and 8% were considered to be drug related. In total, three patients experienced a fatal serious AE, which were not considered to be drug related.
For more information, click here.
To learn more about TK2d and other rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/