FDA rejects Applied Therapeutics' treatment for galactosemia

In the United States, Applied Therapeutics, Inc. faced a significant setback when the FDA issued a Complete Response Letter for its New Drug Application for govorestat, a treatment aimed at Classic Galactosemia. The letter, received on Wednesday, indicates that the FDA concluded its review and found the application unable to be approved in its current form due to deficiencies in the clinical data provided. This rare genetic metabolic disorder, galactosemia, impedes the body's ability to metabolize galactose, consequently leading to the accumulation of toxic metabolites that can cause severe neurological complications. The FDA's feedback is a critical factor for Applied Therapeutics as the company is now evaluating the necessary steps to either resubmit their application or appeal the decision. Following this rejection, Applied Therapeutics plans to request an immediate meeting with the FDA to clarify the requirements for potential resubmission. This unprecedented decision came as a surprise, especially considering that analysts from William Blair had previously expressed confidence in the approval based on strong clinical data that demonstrated the drug's effectiveness for a condition with no available treatments. In light of the FDA's decision, the timeline for a U.S. market launch of govorestat has been pushed back significantly; analysts now estimate that the probability of success for the galactosemia program has fallen to 30%, with a new launch projected for the fourth quarter of 2025. This delay raises questions about the future of govorestat in treating Classic Galactosemia and whether additional clinical trials will be required by the FDA before any further approval efforts can be made. The ambiguities surrounding the requirements laid out by the FDA are a source of concern for both the company and its investors. Despite this unfortunate development for govorestat, William Blair maintains an Outperform rating for Applied Therapeutics, indicating a level of optimism about the company’s other program aimed at Sorbitol Dehydrogenase (SORD) Deficiency, a rare, progressive neuromuscular disease. The company has reported that their SORD clinical trial has met all key goals and provided a robust data package that could facilitate an accelerated approval pathway. Should the FDA grant priority review for SORD, there remains a possibility to start generating revenue by late 2025. Thus, while the setback with govorestat is significant, the overall outlook for Applied Therapeutics may not be wholly negative at this juncture.