New data on investigational therapy for thymidine kinase 2 deficiency presented at Muscular Dystrophy Association (MDA) 2025 Conference
UCB presented positive clinical data for its investigational therapy doxecitine (dC) and doxribtimine (dT) for treating thymidine kinase 2 deficiency (TK2d) at the MDA Conference 2025. The data demonstrated significant benefits in survival and motor function improvements.
Key findings show that in patients with symptom onset ≤12 years, treatment reduced death risk by 92-94% from symptom onset and 87-95% from treatment start. Additionally, 75% of patients regained at least one lost motor milestone, with 22.5% regaining four or more. Ventilatory support needs decreased, with 16.1% reducing usage and another 16.1% discontinuing support entirely.
The therapy was generally well-tolerated, with diarrhea (84.6%-90.9%) being the most common side effect. The treatment is currently under review by US FDA and EMA regulators.
UCB ha presentato dati clinici positivi per la sua terapia sperimentale doxecitina (dC) e doxribtimina (dT) per il trattamento della deficienza di chinasi della timidina 2 (TK2d) alla Conferenza MDA 2025. I dati hanno dimostrato benefici significativi nella sopravvivenza e nei miglioramenti della funzione motoria.
I risultati chiave mostrano che nei pazienti con insorgenza dei sintomi ≤12 anni, il trattamento ha ridotto il rischio di morte del 92-94% dall'insorgenza dei sintomi e dell'87-95% dall'inizio del trattamento. Inoltre, il 75% dei pazienti ha recuperato almeno una pietra miliare motoria persa, con il 22,5% che ha recuperato quattro o più. Le necessità di supporto ventilatorio sono diminuite, con il 16,1% che ha ridotto l'uso e un altro 16,1% che ha interrotto completamente il supporto.
La terapia è stata generalmente ben tollerata, con la diarrea (84,6%-90,9%) come effetto collaterale più comune. Il trattamento è attualmente in fase di revisione da parte della FDA degli Stati Uniti e dei regolatori EMA.
UCB presentó datos clínicos positivos para su terapia investigacional doxecitina (dC) y doxribtimina (dT) para tratar la deficiencia de quinasa de timidina 2 (TK2d) en la Conferencia MDA 2025. Los datos demostraron beneficios significativos en la supervivencia y en las mejoras de la función motora.
Los hallazgos clave muestran que en pacientes con inicio de síntomas ≤12 años, el tratamiento redujo el riesgo de muerte en un 92-94% desde el inicio de los síntomas y en un 87-95% desde el inicio del tratamiento. Además, el 75% de los pacientes recuperó al menos un hito motor perdido, con un 22,5% recuperando cuatro o más. Las necesidades de soporte ventilatorio disminuyeron, con un 16,1% reduciendo el uso y otro 16,1% discontinuando el soporte por completo.
La terapia fue generalmente bien tolerada, siendo la diarrea (84,6%-90,9%) el efecto secundario más común. El tratamiento está actualmente bajo revisión por parte de la FDA de EE. UU. y de los reguladores de la EMA.
UCB는 2025년 MDA 컨퍼런스에서 doxecitine (dC) 및 doxribtimine (dT)의 임상 데이터를 발표하였으며, 이는 티미딘 키나제 2 결핍증 (TK2d) 치료를 위한 것입니다. 데이터는 생존율과 운동 기능 개선에서 상당한 이점을 보여주었습니다.
주요 발견에 따르면, 증상이 발생한 지 ≤12세인 환자에서 치료는 증상 발생 시점에서 92-94%, 치료 시작 시점에서 87-95%의 사망 위험을 감소시켰습니다. 또한, 환자의 75%가 잃어버린 운동 이정표 중 최소 하나를 회복하였으며, 22.5%는 네 개 이상의 이정표를 회복하였습니다. 호흡 보조 필요성도 감소하였으며, 16.1%는 사용을 줄였고, 또 다른 16.1%는 보조를 완전히 중단하였습니다.
이 요법은 일반적으로 잘 견뎌졌으며, 가장 흔한 부작용은 설사(84.6%-90.9%)였습니다. 이 치료는 현재 미국 FDA와 EMA 규제 기관의 검토를 받고 있습니다.
UCB a présenté des données cliniques positives pour sa thérapie expérimentale doxécitine (dC) et doxribtimine (dT) pour le traitement de la déficience en thymidine kinase 2 (TK2d) lors de la conférence MDA 2025. Les données ont démontré des avantages significatifs en matière de survie et d'amélioration de la fonction motrice.
Les résultats clés montrent que chez les patients ayant présenté des symptômes avant l'âge de 12 ans, le traitement a réduit le risque de décès de 92 à 94 % depuis l'apparition des symptômes et de 87 à 95 % depuis le début du traitement. De plus, 75 % des patients ont récupéré au moins une étape motrice perdue, avec 22,5 % récupérant quatre étapes ou plus. Les besoins en assistance ventilatoire ont diminué, avec 16,1 % réduisant leur utilisation et un autre 16,1 % interrompant complètement le soutien.
La thérapie a été généralement bien tolérée, la diarrhée (84,6%-90,9%) étant l'effet secondaire le plus courant. Le traitement est actuellement examiné par la FDA des États-Unis et les régulateurs de l'EMA.
UCB hat positive klinische Daten für seine experimentelle Therapie Doxecitin (dC) und Doxribtimin (dT) zur Behandlung der Thymidinkinase-2-Defizienz (TK2d) auf der MDA-Konferenz 2025 präsentiert. Die Daten zeigten signifikante Vorteile in Bezug auf Überleben und Verbesserungen der motorischen Funktion.
Wichtige Ergebnisse zeigen, dass bei Patienten mit Symptombeginn ≤12 Jahren die Behandlung das Sterberisiko um 92-94% vom Symptombeginn und um 87-95% vom Beginn der Behandlung reduzierte. Darüber hinaus erlangten 75% der Patienten mindestens einen verlorenen motorischen Meilenstein zurück, wobei 22,5% vier oder mehr zurückgewannen. Der Bedarf an Beatmungsunterstützung sank, wobei 16,1% den Einsatz reduzierten und weitere 16,1% die Unterstützung vollständig einstellten.
Die Therapie wurde im Allgemeinen gut vertragen, wobei Durchfall (84,6%-90,9%) die häufigste Nebenwirkung war. Die Behandlung wird derzeit von den US-amerikanischen FDA- und EMA-Behörden überprüft.
- Treatment reduced mortality risk by 92-94% in patients with early onset (≤12 years)
- 75% of patients regained at least one lost motor milestone
- 32.2% of patients improved ventilatory support conditions (16.1% reduced usage, 16.1% discontinued)
- Therapy demonstrated favorable safety profile
- High incidence of diarrhea as side effect (84.6-90.9% of patients)
- Treatment not yet approved by FDA or EMA
- Clinical data highlight survival benefits and improvement in functional motor outcomes associated with treatment with doxecitine (dC) and doxribtimine (dT) - an investigational pyrimidine nucleoside therapy - in people living with thymidine kinase 2 deficiency (TK2d).1,2,3
- Additional patient experience data emphasize the profound physical challenges and severe psychological strain that come with living with TK2d, and the heavy emotional and physical burden experienced by caregivers.4,5
- Across all study populations, pyrimidine nucleoside and/or nucleotide therapy was generally well tolerated.1,2,3
- TK2d is an ultra-rare, life-threatening, genetic mitochondrial disease with no currently approved treatment options.6,7,8,9,10,11
The data show that in individuals with TK2d who were aged 12 years or less when their symptoms first appeared, treatment with pyrimidine nucleoside and/or nucleotide therapy significantly decreased mortality and increased survival.2,3 In addition, treatment also improved functional outcomes irrespective of age of onset, including retaining or regaining motor milestones, and helped stabilize ventilatory and feeding support use.1,2,3 Across all study populations, pyrimidine nucleoside and/or nucleotide therapy was generally well tolerated with diarrhea being the most common treatment emergent adverse event.1,2,3
Thymidine kinase 2 deficiency 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.6,7,8,9,10
"There are no approved therapies or international clinical guidelines for the management of TK2d, therefore we are very excited to share this data with the medical community at MDA," said Donatello Crocetta, Chief Medical Officer at UCB. "The data highlight the positive impact this investigational treatment could have on the lives of people living with this debilitating and life-threatening condition."
Data from participants treated in the doxecitine (dC) and doxribtimine (dT) clinical program were pooled from retrospective and prospective sources and a company-supported expanded access program (EAP). Data from untreated participants were pooled from literature reviews of case series and reports, and a retrospective chart review study. Subgroups were stratified by age of TK2d symptom onset categories and reported for participants with age of TK2d symptom onset ≤12 years and >12 years.
Doxecitine and doxribtimine is currently under regulatory review by US and EU regulatory authorities. The safety and efficacy have not been established, and doxecitine and doxribtimine has not been approved by the US Food and Drug Administration (FDA) nor the European Medicines Agency (EMA).
Key findings from the studies
Improvement in survival:
- Among people living with TK2d with an age of symptom onset 12 years or less, treatment with nucleoside and/or nucleotide therapy reduced risk of death by 92–
94% (hazard ratio=0.06–0.08; p<0.0001) and 87–95% (hazard ratio=0.05–0.13; p<0.0001) in the time from symptom onset and starting treatment, respectively.3
Enhanced functional outcomes:
- Among people living with TK2d who were aged 12 years or less when their symptoms first appeared, following treatment with pyrimidine nucleoside and/or nucleotide therapy,
75.0% (30/40) regained at least one previously lost motor milestone, with22.5% (9/40) regaining four or more motor milestones.2 - In addition, ventilatory support dependency decreased, with
16.1% (5/31) of patients reducing usage time and16.1% (5/31) discontinuing ventilatory support altogether after treatment.2
Safety profile:
- Across all study populations, pyrimidine nucleoside and/or nucleotide therapy was generally well tolerated. Diarrhea (range from
84.6% -90.9% ) was the most reported treatment-emergent adverse event.1,2,3
Impact on quality of life on individuals and caregivers:
- In addition to the data presented on nucleoside and/or nucleotide therapy, patient experience data presented highlight the debilitating physical impacts and severe psychological strain associated with living with TK2d, as well as its impact on caregivers. Many individuals reported the 'extreme' impact the condition has on their quality of life including walking, breathing and eating/swallowing difficulties. Caregivers reported that the constant demands of caregiving and minimal support/respite caused persistent stress and emotional burnout.4,5
Key data presented at MDA
Author | Title | Details |
|
| Survival Analyses in Patients with Thymidine Kinase 2 Deficiency Aged ≤12 Years at Symptom Onset Who Received Pyrimidine Nucleos(t)ide Therapy | Assessed survival and safety in patients with an age of TK2d symptom onset ≤12 years who received pyrimidine nucleoside and/or nucleotide therapy. Treated patients were pooled from retrospective (NCT03701568, NCT05017818) and prospective (NCT03845712) sources and a company-supported expanded access program (EAP); untreated patients were pooled from literature reviews of case series and reports and a retrospective chart review (NCT05017818). |
Functional Outcomes in Patients with Thymidine Kinase 2 Deficiency Aged ≤12 Years at Symptom Onset Who Received Pyrimidine Nucleos(t)ide Therapy | Assessed functional outcomes and safety in patients with an age of TK2d symptom onset ≤12 years who received pyrimidine nucleoside and/or nucleotide therapy. Treated patients were pooled from retrospective (NCT03701568, NCT05017818) and prospective (NCT03845712) sources and a company-supported expanded access program (EAP; functional outcome data not collected). | |
Survival and Functional Outcomes in Patients with Thymidine Kinase 2 Deficiency Aged >12 Years at Symptom Onset Who Received Pyrimidine Nucleos(t)ides | Assessed survival, functional outcomes and safety in patients with an age of TK2d symptom onset >12 years who received pyrimidine nucleoside and/or nucleotide therapy. Treated patients were pooled from retrospective (NCT03701568, NCT05017818) and prospective (NCT03845712) sources and a company-supported expanded access program (EAP). | |
Patients' Lived Experience of Thymidine Kinase 2 Deficiency (TK2d): Results from the Assessment of TK2d Patient Perspectives (ATP) Study | Individuals with genetically confirmed TK2d (or proxy caregivers)were invited to complete an online mixed-methods survey co-created by a patient steering committee. | |
Burden and Impact of Caring for those with Thymidine Kinase 2 Deficiency (TK2d): Results from the Assessment of TK2d Patient Perspectives (ATP) Study | Caregivers of patients with genetically confirmed TK2d were invited to complete an online mixed-methods survey. The survey comprised multiple-choice and open-text questions exploring caregivers' experiences and how caregiving affects their quality of life. |
About thymidine kinase 2 deficiency (TK2d)
Thymidine kinase 2 deficiency 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.6,7,8,9,10 It is estimated that the worldwide prevalence of TK2d is 1.64 [0.5, 3.1] cases per 1,000,000 people.12 The age of TK2d symptom onset is categorized as ≤12 years and >12 years.6,7,8
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.11,13
About doxecitine and doxribtimine
Doxecitine and doxribtimine is a nucleoside therapy that supports mitochondrial DNA replication resulting in increased or stabilized mitochondrial function in patients with TK2d. Pre-clinical data suggest the primary mechanism of action of doxecitine and doxribtimine is the incorporation of nucleosides deoxycytidine (dC) and deoxythymidine (dT) into skeletal muscle mitochondrial deoxyribonucleic acid (mtDNA), which has the potential to restore mitochondrial DNA copy number and improve skeletal muscle function in patients with TK2d.14,15,16
In the
For further information, contact UCB:
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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 9 000 people in approximately 40 countries, the company generated revenue of
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References:
- Scaglia F, et al. Survival and Functional Outcomes in Patients with Thymidine Kinase 2 Deficiency Aged >12 Years at Symptom Onset Who Received Pyrimidine Nucleos(t)ides. https://www.mdaconference.org/abstract-library/survival-and-functional-outcomes-in-patients-with-thymidine-kinase-2-deficiency-aged-12-years-at-symptom-onset-who-received-pyrimidine-nucleostides/. Accessed February 2025.
- Garone C, et al. Functional Outcomes in Patients with Thymidine Kinase 2 Deficiency Aged ≤12 Years at Symptom Onset Who Received Pyrimidine Nucleos(t)ide Therapy. https://www.mdaconference.org/abstract-library/functional-outcomes-in-patients-with-thymidine-kinase-2-deficiency-aged-%e2%
89% a412-years-at-symptom-onset-who-received-pyrimidine-nucleostide-therapy/. Accessed February 2025. - Hirano M, et al. Survival Analyses in Patients with Thymidine Kinase 2 Deficiency Aged ≤12 Years at Symptom Onset Who Received Pyrimidine Nucleos(t)ide Therapy. https://www.mdaconference.org/abstract-library/survival-analyses-in-patients-with-thymidine-kinase-2-deficiency-aged-%e2%
89% a412-years-at-symptom-onset-who-received-pyrimidine-nucleostide-therapy/. Accessed February 2025. - Yeske P, et al. Patients' Lived Experience of Thymidine Kinase 2 Deficiency (TK2d): Results from the Assessment of TK2d Patient Perspectives (ATP) Study. https://www.mdaconference.org/abstract-library/patients-lived-experience-of-thymidine-kinase-2-deficiency-tk2d-results-from-the-assessment-of-tk2d-patient-perspectives-atp-study/. Accessed February 2025.
- Yeske P, et al. Burden and impact of caring for those with thymidine kinase 2 deficiency (TK2d): results from the Assessment of TK2d Patient Perspectives (ATP) study. https://www.mdaconference.org/abstract-library/burden-and-impact-of-caring-for-those-with-thymidine-kinase-2-deficiency-tk2d-results-from-the-assessment-of-tk2d-patient-perspectives-atp-study/. Accessed February 2025.
- 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.
- Wang J, et al. TK2-Related Mitochondrial DNA Maintenance Defect, Myopathic Form. 2018. In: Adam MP, et al. GeneReviews® [Internet].
Seattle (WA): University ofWashington ,Seattle ; 1993–2025. - Garone C, et al. Retrospective natural history of thymidine kinase 2 deficiency. J Med Genet. 2018;55(8):515-21.
- Domínguez-González C, et al. Late-onset Thymidine Kinase 2 Deficiency: A Review of 18 cases. Orphanet J Rare Dis. 2019;14(1):100.
- 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 February 2025.
U.S. FDA TK2d Patient Listening Session. https://www.umdf.org/tk2d-patient-listening-session-january-2022. Accessed February 2025.- Ma Y. Prevalence Estimation of Thymidine Kinase 2 Deficiency: An Ultra-Rare Autosomal Recessive Mitochondrial Disease. Poster presented at: ISPOR Europe; 2023, 12-15 November;
Denmark . - 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.
- Lopez-Gomez C, et al. Deoxycytidine and Deoxythymidine Treatment for Thymidine Kinase 2 Deficiency. Ann Neurol. 2017;81(5):641-52.
- Lopez-Gomez C, et al. Bioavailability and cytosolic kinases modulate response to deoxynucleoside therapy in TK2 deficiency. EBioMedicine. 2019;46:356-367.
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