UCB brings first therapy for rare disease TK2d to EU

Patients in the EU with rare disease thymidine kinase 2 deficiency (TK2d) have their first approved therapy, UCB's Kygevi, after the European Commission cleared the drug "under exceptional circumstances."

Kygevi (doxecitine and doxribtimine) can be used to treat people living with TK2d whose disease started before the age of 12 and "marks a historic milestone for the TK2d community," according to Donatello Crocetta, chief medical officer of Belgium-headquartered UCB.

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 that can be fatal within three years of symptom onset. Many affected individuals lose mobility, require respiratory support, and need assistance with basic functions such as eating.

The number of patients with the disease is hard to estimate, as symptoms can be confused with other neuromuscular disorders like spinal muscular atrophy or general myopathy, but one recent study suggested there were around 500 patients in the top four EU economies and the UK, with a similar number in the US, where UCB's drug was approved as Kygevvi last November.

In the main retrospective study supporting Kygevi's approval, the drug was shown to reduce the risk of death by a massive 95% when compared to a historical cohort of untreated patients. It is a combination of pyrimidine nucleosides designed to integrate into skeletal muscle mitochondrial DNA and compensate for reduced activity of the TK2 enzyme.

The analysis also showed that 84% of Kygevi-treated patients regained one or more motor functions, such as sitting upright unassisted, with 22% of recipients able to come off respiratory support.

Sanofi's Rezurock finally gets EU okay

Meanwhile, Sanofi's Rezurock has finally been cleared in the EU for the treatment of chronic graft-versus-host disease (GvHD), after being turned down last October, around five years after a green light in the US.

The EC has ruled that Rezurock can be used in adults and in children aged 12 years and older with a body weight of at least 40 kg who developed GvHD – a condition in which donor cells attack the body's organs after a transplant – but only "when other treatment options provide limited clinical benefit, are not suitable, or have been exhausted."

It is a conditional approval, which will require Sanofi to run a new clinical trial to confirm the efficacy of the drug, said the pharma group, which acquired Rezurock as part of its $1.9 billion takeover of Kadmon Pharma in 2021. The drug grew nearly 9% to €490 million last year, although fourth-quarter sales fell slightly due to "mandatory public rebates."

The company's interim chief executive, Olivier Charmeil, said the approval was important, as "nearly one in two patients with chronic GVHD require third-line treatment, yet, therapeutic options available for EU patients at this late stage of the disease have remained limited."