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

Applied Therapeutics has encountered another obstacle in its pursuit of approval for govorestat, a selective aldose reductase inhibitor, as the drug failed to meet its primary endpoint in a late-stage clinical trial for sorbitol dehydrogenase deficiency (SORD), a rare subtype of Charcot-Marie-Tooth (CMT) disease.

Phase 2/3 Inspire Study Results

The phase 2/3 Inspire study, involving 56 patients with SORD, failed to demonstrate an improvement in the 10-meter walk-run test (10MWRT) at 12 months compared to placebo. This setback comes just five months after the U.S. Food and Drug Administration (FDA) rejected govorestat for use in children with classic galactosemia.

Despite missing the primary endpoint, Applied Therapeutics highlighted some positive secondary outcomes from the trial:

• 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 levels 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

Applied Therapeutics faces an uphill battle in its efforts to bring govorestat to market. The company's previous application for the drug in classic galactosemia was rejected by the FDA in December 2024. The rejection was accompanied by criticism regarding electronic data deletion by a third-party vendor and mishandling of a dosing error in clinical trials.

Despite these setbacks, Applied Therapeutics remains committed to pursuing approval for govorestat in both CMT-SORD and classic galactosemia. Les Funtleyder, the company's CFO and interim CEO, emphasized the challenges of working with 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 submit an approval request to the FDA for govorestat in CMT-SORD this year, focusing on the positive secondary outcomes and additional data from 24-month MRI scans showing slowed disease progression in treated patients.

Financial Outlook

As Applied Therapeutics navigates these regulatory challenges, concerns about the company's financial stability have emerged. William Blair analysts noted in a May 14 report that Applied had cash and cash equivalents of $50.8 million as of March 31, raising questions about the company's limited cash runway.

The pharmaceutical industry will be closely watching Applied Therapeutics' next moves as it attempts to overcome these clinical and regulatory hurdles in its pursuit of rare disease treatments.