FDA Rejects Applied Therapeutics’ Rare Disease Drug Govorestat, Citing Clinical Application Deficiencies

FDA Rejection:
The FDA issued a Complete Response Letter (CRL) to Applied Therapeutics, rejecting the New Drug Application (NDA) for govorestat, a treatment for classic galactosemia, due to deficiencies in the clinical application12.

Clinical Application Deficiencies:
The FDA cited non-specific deficiencies in the clinical application for govorestat but did not provide detailed reasons for the rejection. Applied Therapeutics plans to request a meeting with the FDA to discuss the deficiencies and potential next steps12.

Galactosemia Background:
Galactosemia is a rare inherited metabolic disorder that leads to severe deficiency of enzymes needed to metabolize galactose. The disease can be fatal in infants and is included in newborn screening tests in the U.S.1.

Govorestat Details:
Govorestat is a small molecule designed to inhibit aldose reductase, an enzyme that converts glucose to sorbitol under oxidative stress conditions. The drug did not meet the main goal of showing a statistically significant improvement in a composite endpoint in the Phase 2 portion of the Phase 1/2 clinical trial but showed systemic improvement over time and reduction in blood levels of galactitol1.

Warning Letter:
The FDA also issued a warning letter to Applied Therapeutics, highlighting issues related to electronic data capture and a dosing error during the study's dose-escalation phase. The company has responded to the FDA's concerns and believes it has resolved any outstanding issues34.

Impact on SORD Development:
The rejection does not affect Applied Therapeutics' plans to develop govorestat for sorbitol dehydrogenase (SORD) deficiency, a rare and progressive neuromuscular disease. The company expects to submit a new drug application for this indication early in the first quarter of 20251.

Sources:

1. https://medcitynews.com/2024/12/applied-therapeutics-galactosemia-rare-metabolic-disease-fda-rejection-govorestat/

2. https://appliedtherapeutics.gcs-web.com/news-releases/news-release-details/applied-therapeutics-receives-complete-response-letter-us-fda

3. https://www.investing.com/news/sec-filings/applied-therapeutics-faces-fda-scrutiny-over-drug-study-93CH-3750438

4. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/applied-therapeutics-inc-696833-12032024