UCB announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending marketing authorization under exceptional circumstances for KYGEVVI (doxecitine and doxribtimine). The treatment is intended for pediatric and adult patients with genetically confirmed thymidine kinase 2 deficiency (TK2d) who had symptom onset at or before 12 years of age. The final decision from the European Commission is expected in the second quarter of 2026.
Donatello Crocetta, Chief Medical Officer at UCB, said, “This positive CHMP opinion marks a turning point in the treatment of TK2d, offering a new chapter of hope and a meaningful step forward for patients, families, and clinicians alike. We are deeply proud to be one step closer to being able to bring the first and only approved treatment for TK2d to the community.”
Caterina Garone, Associate Professor of Medical Genetics at the University of Bologna, Italy, stated, “Doxecitine and doxribtimine treatment is a great example of how robust pre-clinical data can be translated into a clinical program in ultra-rare disease, impacting the natural history of a fatal disorder such as thymidine kinase 2 deficiency. The CHMP positive opinion is a significant step toward potential access to the first treatment option for TK2d in Europe.”
The EMA supported this application through its PRIority MEdicines (PRIME) scheme. This program provides early scientific and regulatory support to medicines that could address unmet medical needs. Marketing authorization under exceptional circumstances may be granted when comprehensive efficacy and safety data cannot be provided due to rarity or ethical concerns related to collecting full information.
TK2d is an ultra-rare genetic mitochondrial disease characterized by progressive muscle weakness. It currently has no approved treatments in Europe beyond supportive care. The disease can affect daily life significantly, often requiring continuous caregiver support. Children with symptom onset before age 12 face high risks of premature death within three years after symptoms begin. Globally, it is estimated that between 0.5 and 3.1 people per million have TK2d.
Supportive evidence for KYGEVVI comes from pooled data from two studies involving patients with genetically confirmed TK2d who showed symptoms at age 12 or younger. These studies evaluated functional outcomes such as motor milestones and need for ventilatory or feeding support, as well as survival rates compared to an external control group matched by age at symptom onset. The most common side effects were gastrointestinal issues like diarrhea, vomiting, and abdominal pain.
The mechanism behind doxecitine and doxribtimine involves their incorporation into mitochondrial DNA in skeletal muscle cells. This process helps restore mitochondrial DNA copy number and improve muscle function in affected patients.
Further details on these clinical trials can be found on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT03845712 and https://clinicaltrials.gov/study/NCT03701568.
UCB is a global biopharmaceutical company headquartered in Brussels that focuses on developing treatments for severe diseases affecting the immune system or central nervous system. In 2024, UCB reported revenues of €6.1 billion and employs over 9,000 people across about 40 countries.
The company noted that forward-looking statements regarding regulatory approvals or future performance are subject to various risks including geopolitical events, regulatory uncertainties, research costs, manufacturing issues, competition from other products or technologies, changes in laws or reimbursement policies, cybersecurity threats, among others.
