UCB drug for rare disease TK2d boosts survival

UCB's experimental medicine for rare disease thymidine kinase 2 deficiency (TK2d) has been shown to reduce the risk of death by a massive 95% in a study, as marketing applications are reviewed in the US and EU.

The retrospective study compared medical records of 38 TK2d patients who had been treated with the combination of doxecitine (dC) and doxribtimine (dT) – a pair of pyrimidine nucleoside and nucleotide drugs – to 69 untreated patients.

While 58% of the untreated patients had died at the time of analysis, all the patients in the treated group were alive. The estimated reductions in risk of death with treatment were between 85% and 93% for time from TK2d symptom onset and between 75% and 91% for time from treatment start, according to the data, which has been published in the journal Neurology.

TK2d is an ultra-rare, progressive, and life-threatening mitochondrial myopathy caused by pathogenic variants of the thymidine kinase 2 gene. It leads to mitochondrial DNA depletion, resulting in severe and progressive muscle weakness. Many affected individuals lose mobility, require respiratory support, and need assistance with basic functions such as eating.

The prevalence of Tk2D is still uncertain, but estimates suggest it could affect around 1.64 people per 100 million, which would point to fewer than 150 cases worldwide.

In addition to the apparent improvement in survival, patients treated with dC/dT saw no loss in motor function milestones – such as the ability to hold the head upright, sit upright, stand, and walk – and in two-thirds of cases (65%) regained at least one. Additionally, three of eight patients who needed to be fed through an enteral tube were able to have their tubes removed after treatment.

The dC/dT regimen is currently under regulatory review by US and EU regulators for TK2d in patients with an age of symptom onset on or before 12 years and could become the first approved therapy for the disease.

UCB acknowledges that the retrospective study has limitations – including possible selection bias, a small number of subjects, and wide confidence intervals in the survival data – but nonetheless points to potential in both reducing the risk of death and improving functional outcomes in TK2d.

The Belgian company is running an open-label phase 2 study of dC/dT in TK2d patients that includes the treatment cohort in the Neurology trial and aims to provide supportive data for dC/dT, if approved.

The therapy has been awarded Priority Medicine (PRIME) status by the EMA, breakthrough status by the FDA, and a Promising Innovative Medicine (PIM) designation in the UK.