Announcement • 7h
UCB Publishes Data Demonstrating Positive Impact Of Kygevvi In Patients With Thymidine Kinase 2 Deficiency
UCB announced the publication of two manuscripts in Brain Communications. One manuscript reports integrated safety and efficacy findings for KYGEVVI (doxecitine and doxribtimine), the first and only approved treatment for adults and pediatric patients with early-onset thymidine kinase 2 deficiency (TK2d) with a symptom onset on or before 12 years of age, demonstrating improved survival and functional outcomes in treated patients, along with acceptable tolerability. A second manuscript features findings from the largest published dataset of untreated patients with TK2d, illustrating the progressive burden of disease and increased risk of early death, thus reinforcing the importance of timely diagnosis and treatment. Key findings from the TK2d Integrated Summary of Efficacy (ISE)/Integrated Summary of Safety (ISS) based on data from 104 treated and 114 untreated patients include: Treatment was generally well tolerated and improved survival and functional outcomes, especially in patients who developed symptoms on or before 12 years of age. In a subgroup of patients with age of TK2d symptom onset on or before 12 years of age, the risk of death was reduced with treatment by 92%–94% from the time of symptom onset. In this same subgroup, patients receiving treatment lived an average of 29.2 years over a 30-year period versus 14.4 years for untreated patients. After treatment initiation, most patients in the same subgroup (75%) regained at least one motor milestone and some (22.5%) regained at least four. Most treatment-emergent adverse events (TEAEs) did not lead to discontinuation; 13.4% discontinued treatment as a result of a TEAE and 23.9% reported at least one TEAE that led to dose reduction. The most frequent TEAE was diarrhea (86%), which was generally mild or moderate and resolved with dose reduction. Key findings from the TK2d Natural Disease Course Study, based on a dataset of 257 untreated patients, one of the largest described to date, confirmed the severe disease burden and high mortality associated with TK2d. Untreated TK2d can have serious effects on daily life and life expectancy, especially for those who develop symptoms at an early age, underlining the urgent need for diagnosis (via genetic testing) and treatments for this ultra-rare disease. Descriptive analyses of survival indicate that TK2d was associated with early death. Of the patients with age of symptom onset on or before 12 years of age, 56.4% died with a median (First Quarter, Third Quarter) age at death of 1.9 (1.0, 3.5) years. Approximately two-thirds of patients with age of symptom onset =2 years (66.7%) and 22.2% of patients with age of symptom onset >2 to =12 years died. Loss of previously acquired motor milestones was prevalent in patients with age of symptom onset on or before 12 years of age, with 81.3% losing at least one milestone and 37.3% losing four or more. Most of these patients started to lose milestones within the first few years of symptom onset. Spontaneous regain of lost milestones was rare. Both ventilatory and feeding support were commonly required regardless of age at onset, underscoring significant respiratory and nutritional disease burden of the disease. Approved by the U.S. Food and Drug Administration (FDA) in November 2025, and the European Medicines Agency (EMA) in March 2026, KYGEVVI is a powder for oral solution indicated for the treatment of TK2d in adults and pediatric patients with an age of symptom onset on or before 12 years. Kygevvi is the first treatment approved for early-onset TK2d. KYGEVVI is indicated for the treatment of thymidine kinase 2 deficiency (TK2d) in adult and pediatric patients with an age of symptom onset on or before 12 years. Elevated liver transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] levels were reported in patients treated with KYGEVVI. Obtain baseline liver transaminase (ALT, AST) and total bilirubin levels in patients prior to treatment initiation with KYGEVVI. If signs or symptoms consistent with liver injury are observed, interrupt treatment with KYGEVVI until liver transaminase (ALT, AST) and total bilirubin levels have either returned to baseline or stabilized at a new baseline value. Consider permanently discontinuing KYGEVVI if signs or symptoms consistent with liver injury persist or worsen. Monitor liver transaminases and total bilirubin levels yearly and as clinically indicated. Diarrhea and vomiting leading to hospitalization, dose reduction, and permanent discontinuation were reported in patients treated with KYGEVVI. Based on the severity of the diarrhea and/or vomiting, reduce the dosage of KYGEVVI or interrupt treatment until diarrhea and/or vomiting improves or returns to baseline. Consider restarting KYGEVVI at the last tolerated dose, and increase the dose as tolerated. For persistent or recurring diarrhea and/or vomiting, consider discontinuing KYGEVVI permanently and provide supportive care with electrolyte repletion as clinically indicated. The most common adverse reactions (incidence =5%) are diarrhea, abdominal pain (including abdominal pain upper), vomiting, alanine aminotransferase increased (ALT), and aspartate aminotransferase increased (AST). TK2d is an ultra-rare, life-threatening, genetic mitochondrial disease characterized by progressive (worsening over time) and severe muscle weakness (myopathy). There previously had been no approved treatment options beyond supportive [palliative] care. TK2d can develop at any point in a patient's life. Because long diagnostic journeys and misdiagnoses are common for patients with mitochondrial diseases, people with TK2d may be diagnosed years after symptom onset. Patients aged =12 years at TK2d symptom onset face a high risk of premature death, often occurring within 3 years after symptom onset. It is estimated that the worldwide prevalence of TK2d is 1.64 [0.5, 3.1] cases per 1,000,000 people.