FDA Alignment Hints at Progress for Applied Therapeutics' Rare Disease Drug

Applied Therapeutics may have reached a crucial agreement with the U.S. Food and Drug Administration (FDA) regarding the development path for govorestat, its experimental treatment for sorbitol dehydrogenase deficiency (SORD). This potential breakthrough comes despite earlier setbacks in clinical trials and highlights the complex landscape of rare disease drug development.

New Confirmatory Study Signals Potential FDA Agreement

A new study for govorestat, an aldose reductase inhibitor, has been posted on clinicaltrials.gov, suggesting that Applied Therapeutics and the FDA may have found common ground on the drug's development strategy. The study, which appeared on the clinical trials database on September 25, 2025, aims to enroll 155 patients across 16 global sites.

The trial is designed to evaluate the long-term effects of govorestat on functional, clinical, and patient-reported outcomes in individuals diagnosed with Charcot-Marie-Tooth Type 2 or distal Hereditary Motor Neuropathy due to SORD. With a primary completion date set for October 2028, this confirmatory study could play a crucial role in govorestat's regulatory journey.

William Blair analysts interpreted the study's posting as a positive sign, noting that it might indicate the FDA found previously collected data sufficient to support an accelerated approval for govorestat in SORD patients. However, Applied Therapeutics has yet to officially confirm this alignment with the regulatory agency.

Overcoming Previous Clinical Setbacks

The potential progress comes in the wake of govorestat's failure to meet its primary endpoint in the Phase II/III INSPIRE trial earlier this year. In May, the drug did not significantly improve scores on the 10-meter walk-run test at 12 months compared to placebo. Despite this setback, Applied Therapeutics remained committed to pursuing a new drug application for govorestat, focusing on positive secondary outcomes and significant reductions in blood sorbitol levels, a key disease biomarker.

Evan Bailey, Senior Vice President of Clinical Development at Applied Therapeutics, expressed optimism about the drug's potential, stating, "We are encouraged by the breadth of data supporting govorestat's ability to significantly lower blood sorbitol levels and positively impact both functional and patient-reported outcomes."

Financial Considerations and Future Outlook

As Applied Therapeutics navigates the regulatory landscape, financial considerations loom large. As of June 30, the company reported $30.4 million in cash and cash equivalents. William Blair analysts flagged this as a potential concern, noting the "increased financial risk" given the company's "limited cash runway."

The rare genetic condition SORD is characterized by the accumulation of sorbitol sugars in nerves, leading to sensory loss and muscle weakness. Govorestat's mechanism of action involves disabling the aldose reductase enzyme, thereby disrupting the pathway that results in sorbitol production.

While the posting of the new confirmatory study suggests progress, Applied Therapeutics has not yet provided official confirmation of its alignment with the FDA. As the pharmaceutical industry watches closely, the coming months may prove critical for both the company and patients affected by this rare disease.