Applied Therapeutics is awaiting a decision from the U.S. Food and Drug Administration (FDA) regarding its New Drug Application (NDA) for govorestat, an investigational aldose reductase inhibitor, for the treatment of galactosemia. The FDA's target action date is November 28.
Galactosemia is a rare, genetic, metabolic disorder affecting approximately 3,000 diagnosed individuals in the U.S. It is characterized by the body's inability to properly break down galactose, leading to the accumulation of galactitol, a toxic metabolite that damages the nervous system. Patients with galactosemia often experience cognitive, behavioral, motor, and speech problems. Currently, there are no approved therapies specifically targeting the underlying metabolic defect in galactosemia.
Govorestat's Mechanism and Clinical Data
Govorestat is designed to address the root cause of galactosemia by inhibiting the aldose reductase enzyme, which is responsible for converting galactose into galactitol. The NDA submission is supported by data from the Phase I/II ACTION-Galactosemia study in adults and the Phase III ACTION-Galactosemia Kids study in pediatric patients, along with preclinical trial results.
The ACTION-Galactosemia study demonstrated a rapid and sustained reduction in galactitol levels in adult patients treated with govorestat. Significant reductions were observed as early as day one and persisted throughout the one-month study period. The ACTION-Galactosemia Kids study indicated clinical benefits in pediatric patients, with improvements observed in activities of daily living, cognition, tremors, and behavior.
Regulatory History
The FDA initially granted Priority Review to govorestat with a target action date of August 28. However, in March 2024, the FDA extended the review period by three months to allow for further analysis of supplemental data submitted by Applied Therapeutics. In September, the FDA announced that it would not convene an advisory committee meeting to discuss the application.
