New data on investigational therapy for thymidine kinase 2 deficiency presented at Muscular Dystrophy Association (MDA) 2025 Conference - UCB

UCB announced positive data from studies involving its investigational pyrimidine nucleoside therapy, doxecitine (dC) and doxribtimine (dT), in people living with thymidine kinase 2 deficiency (TK2d), at this year’s MDA Clinical and Scientific Conference, Dallas, Texas. 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. 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. Across all study populations, pyrimidine nucleoside and/or nucleotide therapy was generally well tolerated with diarrhea being the most common treatment emergent adverse event.

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. “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

1. 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.

2. 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, with 22.5% (9/40) regaining four or more motor milestones. In addition, ventilatory support dependency decreased, with 16.1% (5/31) of patients reducing usage time and 16.1% (5/31) discontinuing ventilatory support altogether after treatment.

3. 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.

4. 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.