Metabolic Regulator Shows Promise for Life-Saving Treatment of Thymidine Kinase Deficiency Disorders 

In a global phase 2 study of pyrimidine nucleoside substrate enhancement therapy (SET) (MT1621; Modis Therapeutics/Zogenix, Oakland, CA) for treating thymidine kinase 2 (TK2) deficiency all treated participants survived. Most individuals treated with SET had improved (68%) or stabilized (26%) motor domain functions compared to baseline. A subset of participants had profound responses, including: 

•  3 participants who regained ambulation and 1 who walked for the first time, a
• participant who had been on continuous mechanical ventilation discontinued all respiratory support, and 
• 3 of 8 participants who had feeding tubes were able to have them removed.

“TK2 deficiency is an inherited mitochondrial DNA depletion disorder that causes severe muscle weakness that progresses until patients, typically children, lose the ability to stand, walk, eat, and breathe independently,” said Michio Hirano, MD, chief of the division of neuromuscular medicine, Columbia University. “This is a landmark study demonstrating that nucleoside therapy provided meaningful clinical benefit to patients across the spectrum of TK2 deficiency.”

“The results from this study demonstrate the potential of our investigational drug, MT1621, to improve outcomes in patients with TK2 deficiency and to significantly alter the course of disease,” said Joanne Quan, MD, chief medical officer, Modis Therapeutics. “We look forward to continuing the development of MT1621, with the goal of bringing it to patients as quickly as possible.”
In the global RETRO trial (NCT03701568), 38 participants with TK2 deficiency were given a fixed combination treatment of 2 pyrimidine nucleosides (dC/dT) and observed for changes from their baseline status. Participants median age at disease onset was 2.5 years. In this prospective trial, participants received SET for a median of 77 weeks (range 92 days-7 years).