Applied Therapeutics' Rare Disease Drug Faces Another Setback in Phase 3 Trial

Applied Therapeutics has announced that its rare disease drug, govorestat, has failed to meet the primary endpoint in another late-stage clinical trial. This setback comes just five months after the U.S. Food and Drug Administration (FDA) rejected the drug for a different indication.

Clinical Trial Results and Implications

The phase 2/3 Inspire study, which evaluated govorestat in 56 patients with sorbitol dehydrogenase deficiency (SORD), a subtype of Charcot-Marie-Tooth (CMT) disease, did not demonstrate a significant improvement in the 10-meter walk-run test (10MWRT) at 12 months compared to placebo. This primary endpoint failure adds to the challenges faced by the selective aldose reductase inhibitor.

Despite the disappointing primary outcome, Applied Therapeutics highlighted some positive secondary objectives:

• A statistically significant improvement in the Charcot Marie Tooth Health Index, a patient-reported outcome measure
• Lowered blood sorbitol levels
• A correlation between changes in sorbitol and changes in 10MWRT

Dr. Evan Bailey, Senior Vice President of Clinical Development at Applied, expressed optimism about the drug's potential: "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 including stability and mobility at up to two years of treatment."

Regulatory Challenges and Future Plans

The failure of the Inspire study follows a series of regulatory setbacks for govorestat. In December 2024, the FDA rejected an application for the drug's use in children with classic galactosemia. This rejection was accompanied by criticism of the company's handling of electronic data and a dosing error in previous trials.

Despite these challenges, Applied Therapeutics remains committed to pursuing FDA approval for govorestat in both CMT-SORD and classic galactosemia. Les Funtleyder, Applied's Chief Financial Officer and Interim CEO, emphasized the complexities of developing treatments for newly discovered rare diseases: "With newly discovered and rare diseases comes an ever-changing landscape of emerging hypotheses and research, requiring the need for flexibility and fluidity in the clinic."

The company plans to conduct further analysis of the Inspire trial results to support potential future regulatory interactions with the FDA regarding govorestat for the treatment of CMT-SORD. Applied Therapeutics aims to submit an approval request to the FDA for govorestat in CMT-SORD this year, although the timeline for resubmission in galactosemia remains unclear.

Financial Outlook

As of March 31, Applied Therapeutics reported cash and cash equivalents of $50.8 million. However, industry analysts have expressed concerns about the company's financial position. William Blair analysts noted in a May 14 report, "We also see the company as bearing increased financial risk given its limited cash runway."

The ongoing regulatory challenges and clinical trial setbacks may further impact the company's financial stability and its ability to bring govorestat to market. As Applied Therapeutics navigates these hurdles, the pharmaceutical industry will be watching closely to see how the company addresses its regulatory issues and advances its rare disease pipeline.