Govorestat NDA for Classic Galactosemia Faces No FDA Advisory Committee, PDUFA Date on Track
Key Insights
Applied Therapeutics' govorestat, a CNS penetrant Aldose Reductase Inhibitor, is under NDA review for treating Classic Galactosemia (search), a rare metabolic disorder.
The FDA has communicated that an Advisory Committee meeting, previously scheduled for October 9, 2024, will no longer be required for the govorestat NDA review.
The FDA's Priority Review of the govorestat NDA is proceeding as planned, with alignment on post-marketing requirements expected in October 2024.
Applied Therapeutics recently announced that the FDA has completed its late-cycle review meeting for the New Drug Application (NDA) of govorestat for the treatment of Classic Galactosemia (search). The FDA has communicated that an Advisory Committee meeting will no longer be required. The Prescription Drug User Fee Act (PDUFA) target action date remains on track for November 28, 2024.
Regulatory Update
The FDA informed Applied Therapeutics that the Priority Review of the NDA is continuing as planned, with alignment on post-marketing requirements expected in October 2024. This regulatory update provides a clearer path for govorestat, potentially expediting its availability to patients with Classic Galactosemia (search).
Management Commentary
Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics, expressed optimism about the ongoing dialogue with the FDA. "We are incredibly pleased by the ongoing collaborative dialogue with the FDA during the NDA review process, and we look forward to continuing to work together with the agency to bring the first potential treatment to Classic Galactosemia (search) patients," Shendelman stated.
About Galactosemia
Classic Galactosemia (search) is a rare genetic metabolic disease characterized by the body's inability to properly metabolize galactose, a simple sugar. This deficiency leads to the accumulation of galactitol, a toxic metabolite, causing neurological complications such as speech and cognitive impairments, behavioral issues, motor skill deficits, juvenile cataracts, and ovarian insufficiency in females. In the US, approximately 3,000 individuals are affected, with 80 new births annually, while the EU sees around 4,000 patients and 120 new births each year. Newborn screening is mandatory in the US and most EU countries, facilitating early diagnosis and intervention.
Govorestat (AT-007): A Potential Treatment
Govorestat is a CNS-penetrant Aldose Reductase Inhibitor (ARI) being developed by Applied Therapeutics for various rare neurological diseases, including Galactosemia (search), SORD Deficiency (search), and PMM2-CDG (search). Clinical studies in children with Galactosemia (ages 2-17) have demonstrated that govorestat provides clinical benefits in activities of daily living, behavioral symptoms, cognition, fine motor skills, and tremor. Furthermore, govorestat significantly reduces plasma galactitol levels in both adult and pediatric patients, addressing the root cause of tissue damage and long-term complications associated with Galactosemia.
Clinical Trial Data
In the Phase 3 INSPIRE trial involving patients with SORD Deficiency (search), interim analysis at 12 months showed a statistically significant reduction in blood sorbitol levels with govorestat treatment compared to placebo (p<0.05). A statistically significant correlation was also observed between sorbitol reduction and improvements in clinical outcomes, including the 10-meter walk run test, dorsiflexion, and 6-minute walk test. Additionally, govorestat demonstrated highly statistically significant effects on the CMT Health Index (CMT-HI), benefiting lower limb function, mobility, fatigue, pain, sensory function, and upper limb function.
Regulatory Designations
Govorestat has received Orphan Medicinal Product Designation from the European Medicines Agency (EMA) for both Galactosemia (search) and SORD Deficiency (search). The U.S. Food and Drug Administration (FDA) has granted it Orphan Drug Designation for the treatment of Galactosemia, PMM2-CDG (search), and SORD Deficiency; Pediatric Rare Disease designation for Galactosemia and PMM2-CDG; and Fast Track designation for Galactosemia.