Results published in Neurology highlight a 95% reduction in risk of death with pyrimidine nucleos(t)ide therapy in patients with thymidine kinase 2 deficiency (TK2d)

• First published data from a multicenter retrospective chart review study to explore the safety and efficacy of pyrimidine nucleoside and/or nucleotide therapy in patients with thymidine kinase 2 deficiency (TK2d).¹
• Neurology published results from a multicenter retrospective chart review study of pyrimidine nucleoside and/or nucleotide therapy which showed a reduction in the risk of death by 95%.¹ 
• UCB’s pyrimidine nucleoside therapy is currently under regulatory review by US and EU regulatory authorities. If approved, it will become the first and only treatment for TK2d in patients with an age of symptom onset on or before 12 years.²

Brussels (Belgium) October 13, 2025 – 07:00 (CET) – UCB, a global biopharmaceutical company, today announced that Neurology has published results from a multicenter retrospective chart review study of investigational pyrimidine nucleoside and/or nucleotide therapy in people living with thymidine kinase 2 deficiency (TK2d). The results indicated that pyrimidine nucleoside and/or nucleotide therapy may reduce risk of death and can impact functional outcomes in patients with TK2d.¹ 

TK2d is an ultra-rare, life-threatening, genetic mitochondrial disease characterized by progressive and severe muscle weakness (myopathy), which can impact the ability to walk, eat, and breathe independently.^3,4,5,6,7

Key findings of the Neurology publication include:

• No deaths among treated patients (0/38), compared to 58% mortality in untreated patients (40/69).
• Estimated reductions in risk of death with treatment were between 85% and 93% (HR 0.067–0.147) for time from TK2d symptom onset and between 75% and 91% (HR 0.091–0.251) for time from treatment start. Treated patients showed a 95% reduction in risk of death by exact conditional logistic regression analysis.¹ 
• Before treatment, around 71% (27/38) of patients lost ≥1 motor milestone and 29% (11/38) of patients lost ≥4 motor milestones. During treatment, no patients lost motor milestones, and after starting treatment, of those who had lost motor milestones, 65% (17/26) regained at least one motor milestone.¹ 
• Over 50% (19/38) of the patients were using ventilatory support before treatment. Among those who received treatment, 29% (6/21) experienced a reduction in their need for ventilatory support.¹ 

Safety information: 

• Most treatment-emergent adverse events (TEAEs) were mild and did not lead to discontinuation.1 The most common TEAEs were diarrhea (overall 26/38, 68% those treated with age of symptom onset of ≤12 years, 18/29, 62%), increased blood creatine kinase (CK; overall, 9/38, 23%; those treated with age of symptom onset of ≤12 years, 8/29, 28%), pyrexia (overall, 6/38, 16%; those treated with age of symptom onset of ≤12 years, 6/29, 21%), increased alanine aminotransferase (ALT; overall, 6/38, 16%; those treated with age of symptom onset of ≤12 years, 5/29, 17%), and increased aspartate aminotransferase (AST; overall, 5/38, 13%; those treated with age of symptom onset of ≤12 years, 4/29, 14%).¹ 

Study limitations: 

• The study's limitations included potential selection bias due to differing eligibility criteria (mitigated, in part, by a patient matching algorithm), large confidence intervals from no deaths in the treated group complicating result precision, low patient numbers due to the rarity of the condition, and challenges in comparing treated and untreated groups due to variability in data collection and assessment protocols, as well as missing additional data on patient health metrics.¹

"Publication of these results in Neurology, a leading medical journal, underscores the significance of these data for the TK2d community," said Cristina Domínguez-González, Neurology Specialist, University Hospital 12 de Octubre, Madrid, and lead author. "Our study showed positive results, with pyrimidine nucleoside and/or nucleotide therapy demonstrating improvement in survival. These findings highlight the potential of pyrimidine nucleoside and/or nucleotide therapy as a clinically important therapeutic option, offering hope for a new standard of care if approved by the regulatory authorities."

“TK2 deficiency is an ultra-rare, progressive mitochondrial disorder with no approved therapies or internationally recognized clinical guidelines, leaving patients and families with only supportive disease management,” said Donatello Crocetta, Chief Medical Officer at UCB. “As part of our mission to address severe, underserved diseases, the publication of these findings marks an important milestone — reinforcing our commitment to advancing science into potential first-in-class medicines for this community.”

About thymidine kinase 2 deficiency (TK2d)

Mitochondrial diseases, like TK2d, affect energy-demanding parts of the body such as muscles, heart, and brain.^4,5,8 TK2d is generally categorized as: age of symptom onset ≤12 years and >12 years.3,4,5 TK2d presents with varying severity depending on the age of onset, with cases in the population with age of symptom onset ≤12 years typically being the most rapidly progressing  and cases in the population with age of symptom onset >12 years slower progressing.^3,4,5 The estimated worldwide prevalence of TK2d is 1.64 [0.5, 3.1] cases per 1,000,000 people.⁹ 

TK2d profoundly affects multiple health, physical, quality-of-life, and psychosocial domains, as children struggle to achieve developmental milestones or lose them, and adults lose functional independence with challenges in breathing, eating, and walking.^10,11

About doxecitine and doxribtimine

Administration of doxecitine and doxribtimine is intended to incorporate the pyrimidine nucleosides, deoxycytidine and deoxythymidine, into skeletal muscle mitochondrial deoxyribonucleic acid (DNA). This action restores mitochondrial DNA copy number in TK2d mutant mice, as suggested by preclinical data.^12,13,14

The safety and efficacy of doxecitine and doxribtimine combination therapy has not been established and is not currently approved for use by any regulatory authority worldwide. It is currently under regulatory review by US and EU regulatory authorities.

For further information, contact UCB: 

Global Communications
Nick Francis
T: +44 7769 307745
 nick.francis@ucb.com 

Corporate Communications, Media Relations
Laurent Schots 
T +32.2.559.92.64 
Laurent.schots@ucb.com  

Investor Relations
Antje Witte 
T +32.2.559.94.14 
antje.witte@ucb.com 

About UCB
UCB, Brussels, Belgium (www.ucb.com), is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 9000 people in approximately 40 countries, the company generated revenue of € 6.1 billion in 2024. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news

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References:

1. Domínguez-González C, et al. Pyrimidine Nucleos(t)ide Therapy in Patients With Thymidine Kinase 2 Deficiency. Neurology. 2025;105(6):e213908. 
2. Thymidine kinase 2 deficiency. National Organization for Rare Disorders. Updated April 3, 2025. https://rarediseases.org/rare-diseases/thymidine-kinase-2-deficiency/. Accessed September  2025.
3. Berardo A, et al. Advances in Thymidine Kinase 2 Deficiency: Clinical Aspects, Translational Progress, and Emerging Therapies. J Neuromuscul Dis. 2022;9(2):225-35.
4. Wang J, et al. TK2-Related Mitochondrial DNA Maintenance Defect, Myopathic Form. 2018. In: Adam MP, et al. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025.
5. Garone C, et al. Retrospective natural history of thymidine kinase 2 deficiency. J Med Genet. 2018;55(8):515-21.
6. Domínguez-González C, et al. Late-onset thymidine kinase 2 deficiency: a review of 18 cases. Orphanet J Rare Dis. 2019;14(1):100.
7. National Institutes of Health. TK2-related mitochondrial DNA depletion syndrome, myopathic form. https://medlineplus.gov/genetics/condition/tk2-related-mitochondrial-dna-depletion-syndrome-myopathic-form/#genes. Accessed September 2025.
8. Cleveland Clinic. Mitochondrial Diseases. https://my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases. Accessed September 2025.
9. Ma Y. 2023. ISPOR Europe. EPH140.
10. Amtmann D, et al. The impact of TK2 deficiency syndrome and its treatment by nucleoside therapy on quality of life. Mitochondrion. 2023;68:1-9.
11. United Mitochondrial Disease Foundation. TK2d Patient Listening Session. https://www.umdf.org/tk2d-patient-listening-session-january-2022. Accessed September 2025.
12. Lopez-Gomez C, et al. Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency. Ann Neurol. 2017;81(5):641-52.
13. Lopez-Gomez C, et al. Bioavailability and cytosolic kinases modulate response to deoxynucleoside therapy in TK2 deficiency. EBioMedicine. 2019;46:356-67.
14. ClinicalTrials.gov. NCT04581733. https://clinicaltrials.gov/study/NCT04581733#contacts-and-locations. Accessed September 2025.