Repligen Corporation announced the initiation of a Phase 1/2 trial of triacetyluridine (RG2133), a prodrug of uridine, in patients with mitochondrial disease.The open-label study will enroll 12 patients with a confirmed diagnosis of mitochondrial disease. Each patient will receive escalating doses of RG2133 over four weeks.Patients will be evaluated with a variety of criteria to determine if RG2133 treatment is well tolerated and whether there was an impact on symptoms including renal function, seizures or cardiac function.The clinical trial will be initiated at the University of California, San Diego (UCSD) Metabolic and Mitochondrial Research Center and may include additional sites in North America.
Separately, Repligen announced today that the Food and Drug Administration ("FDA") has granted Repligen Orphan Drug Designation for the use of triacetyluridine in mitochondrial disease.If RG2133 is approved by the FDA for use in mitochondrial disease, it will receive market exclusivity for a period of seven years following approval.
"We are pleased to announce the initiation of our second clinical trial for RG2133," stated Walter C. Herlihy, President and CEO of Repligen. "Published data on the use of triacetyluridine in this population suggest that uridine supplementation is well tolerated and can produce significant benefits in some patients."
Mitochondria are structures essential for many cellular functions including energy production.Inborn forms of mitochondrial disease affect approximately 20,000 people in the United States and result in symptoms including seizures, skeletal and heart muscle weakness, movement disorders, kidney disease and growth and development delays in children.In its severest forms, mitochondrial disease can lead to death before the age of 10.Normal mitochondrial function is required for the synthesis of uridine, a precursor to all pyrimidines in the cell.Pyrimidines are used in dozens of essential biochemical reactions, in addition to the basic synthesis of RNA and DNA. When mitochondrial function is impaired, pyrimidine synthesis may also be deficient.This deficiency may be overcome by treatment with pyrimidine derivatives like RG2133.The UCSD Mitochondrial and Metabolic Disease Center is a leading center for research, diagnosis and treatment of mitochondrial disease.