FDA Issues Complete Response Letter for Applied Therapeutics' Govorestat in Classic Galactosemia
Key Insights
The FDA issued a Complete Response Letter for govorestat, citing deficiencies in the clinical application for treating Classic Galactosemia (search).
Govorestat demonstrated rapid galactitol (search) reduction and clinical benefits in pediatric patients during Phase 3 trials, showing a favorable safety profile.
Applied Therapeutics plans to meet with the FDA to discuss requirements for NDA resubmission or appeal, while continuing govorestat's development for SORD Deficiency.
Applied Therapeutics, Inc. has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding its New Drug Application (NDA) for govorestat, a central nervous system (CNS)-penetrant aldose reductase inhibitor (ARI), intended for the treatment of Classic Galactosemia (search). The FDA stated that it cannot approve the NDA in its current form due to deficiencies identified within the clinical application.
Clinical Trial Efficacy
Despite the FDA's decision, govorestat has demonstrated promising results in clinical trials. Notably, it has shown rapid and sustained reductions in galactitol (search) levels, which correlated with meaningful improvements in clinical outcomes among pediatric patients. The Phase 3 registrational ACTION-Galactosemia Kids study, involving children aged 2-17 with Galactosemia, revealed that govorestat treatment led to improvements in activities of daily living, behavioral symptoms, cognition, fine motor skills, and tremor. Furthermore, significant reductions in plasma galactitol levels were observed in both adult and pediatric patients with Galactosemia.
Extensive Data Support
Additional supportive studies have contributed robust efficacy and safety data from over 185 patients with Classic Galactosemia (search) monitored over a three-year period. The results from both the ACTION-Galactosemia Kids study and the Phase 1/2 ACTION-Galactosemia study in adult patients have been published in the Journal of Clinical Pharmacology.
Future Steps and SORD Deficiency Program
Applied Therapeutics is currently evaluating the FDA's feedback and intends to promptly request a meeting with the agency. The purpose of this meeting is to discuss the necessary steps for a potential resubmission of the NDA or to explore options for appealing the decision. The company remains committed to advancing govorestat as a therapeutic option for Classic Galactosemia (search).
In parallel, Applied Therapeutics is also developing govorestat for the treatment of Sorbitol Dehydrogenase (SORD) Deficiency (search), a rare and progressive neuromuscular disease. The NDA submission for this indication is anticipated in the first quarter of 2025. It is important to note that the review and potential approval of govorestat for SORD Deficiency are independent of the ongoing regulatory process for Classic Galactosemia (search).