Kygevvi (doxecitine and doxribtimine) for thymidine kinase 2 deficiency: a turning point for an ultra-rare mitochondrial disorder

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2026年6月8日

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Nwamaka Chidera Bob-Ume,
Esther Oluwafunmilayo Omotoso,
Chizoba Sandra Bob-Ume,
JohnPaul Steve Akpabio,
Stella Steve Akpabio,
Kosisochukwu Chinenye Bob-Ume,
Ebelechukwu Isioma Bob-Ume,
PraiseGod Monday Ebenezer,
Joseph Uso Lot,
Precious Nmesomachi Orji,
Bernard Dominic Okon,
Rita Chinecherem Amaugo,
Ediomo Joseph Bright,
Abdulhakeem Abdulsalam Oladipupo

摘要

Purpose

Thymidine kinase 2 deficiency (TK2d) is an ultra-rare, autosomal recessive mitochondrial deoxyribonucleic acid (DNA) depletion syndrome. It causes progressive muscle weakness, respiratory failure, and carries high early mortality.

Until recently, management was limited to supportive care, and no treatment could alter the course of the disease. This clinical review discusses the mitochondrial pathophysiology of TK2d, summarizes the preclinical rationale and clinical evidence for pyrimidine nucleos(t)ide therapy, and places in context the approval of Kygevvi (doxecitine and doxribtimine) by the United States (U.S.) Food and Drug Administration (FDA) in November 2025, the first approved disease-modifying therapy for TK2d.

Methods and results

Multicenter retrospective data show that pyrimidine nucleos(t)ide therapy achieves an 85–93% relative reduction in mortality compared to untreated natural history cohorts, with 65.4% of treated patients regaining at least one major functional milestone.

Conclusion

The approval of Kygevvi shifts the care approach from reactive palliation to proactive disease modification. Early genetic diagnosis, prompt treatment, coordinated multidisciplinary care, and equitable global access are now the essential priorities.