Applied Therapeutics announced that the U.S. Food and Drug Administration (FDA) has extended the review period for the New Drug Application (NDA) for govorestat (AT-007), a potential treatment for Classic Galactosemia, by three months. The new Prescription Drug User Fee Act (PDUFA) target action date is set for November 28, 2024.
The FDA stated that additional time is needed to review supplemental analyses of previously submitted data provided by Applied Therapeutics in response to routine information requests. The FDA has classified this additional information as a Major Amendment to the NDA.
Govorestat's Clinical Data and Potential Impact
The NDA for govorestat is supported by data demonstrating rapid and sustained reduction in galactitol levels, which correlated with meaningful clinical benefits in pediatric patients. The submission package included clinical outcomes data from the Phase 3 ACTION-Galactosemia Kids study (children aged 2-17), the Phase 1/2 ACTION-Galactosemia study (adult patients), and preclinical data. These studies suggest a favorable safety profile for the drug.
Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics, stated, “While the PDUFA action date extension represents a delay, we remain confident in the potential for govorestat approval for Galactosemia, and we will continue to work closely with the FDA throughout the review process.” She also emphasized the company's commitment to maintaining the expanded access program for govorestat to ensure that patients with Galactosemia can continue to receive this important treatment.
Galactosemia: An Unmet Medical Need
Galactosemia is a rare genetic metabolic disease characterized by the body's inability to properly metabolize galactose, a simple sugar found in foods and produced endogenously. Improper metabolism leads to the conversion of galactose into galactitol, a toxic metabolite that causes neurological complications such as speech deficiencies, cognitive impairment, behavioral issues, and motor skill deficits. It can also result in juvenile cataracts and ovarian insufficiency in women. Approximately 3,000 patients in the US and 4,000 in the EU suffer from Galactosemia, with 80 and 120 new births per year, respectively. Newborn screening is mandatory in the US and most EU countries, facilitating early diagnosis.
Govorestat (AT-007): A Novel Approach
Govorestat is an investigational, novel Aldose Reductase Inhibitor (ARI) designed to penetrate the central nervous system (CNS). It is currently in development for treating several rare neurological diseases, including Galactosemia, SORD Deficiency, and PMM2-CDG. Clinical studies in children with Galactosemia (aged 2-17) have shown that govorestat provides clinical benefits in activities of daily living, behavioral symptoms, cognition, fine motor skills, and tremor. The drug also significantly reduces plasma galactitol levels in both adults and children, addressing the toxic metabolite responsible for long-term complications.
Govorestat is also being evaluated in the Phase 3 INSPIRE trial for SORD Deficiency, comparing AT-007 to placebo in approximately 50 patients aged 16-55 in the U.S. and Europe. Interim analysis at 12 months showed statistically significant reduction in sorbitol levels and highly statistically significant effects on the CMT Health Index (CMT-HI).
Regulatory Designations and Future Outlook
Govorestat has received Orphan Medicinal Product Designation from the European Medicines Agency (EMA) for both Galactosemia and SORD Deficiency. It also holds Orphan Drug Designation from the FDA for Galactosemia, PMM2-CDG, and SORD Deficiency, as well as Pediatric Rare Disease designation for Galactosemia and PMM2-CDG, and Fast Track designation for Galactosemia. Applied Therapeutics has also submitted a Marketing Authorization Application (MAA) to the EMA for govorestat for the treatment of Classic Galactosemia, with a decision expected in the fourth quarter of 2024.
