Applied Therapeutics Faces Uncertainty in Rare Disease Drug Development

Applied Therapeutics, a New York-based biotech company, is navigating a complex regulatory landscape for its lead asset, govorestat, a selective aldose reductase inhibitor targeting rare diseases. The company's recent non-update highlights ongoing challenges in the pharmaceutical industry, particularly in the realm of rare disease drug development.

FDA Discussions and Trial Design Uncertainty

Applied Therapeutics recently met with the FDA to discuss the path forward for govorestat in treating Charcot-Marie-Tooth sorbitol dehydrogenase deficiency (CMT-SORD), a rare subtype of CMT. The company is awaiting official minutes from this meeting, expected within 30 days, before finalizing its regulatory submission plan. This delay underscores the complexities involved in rare disease drug approvals.

The emergence of a new phase 3 clinical trial listing for govorestat has sparked speculation among investors. This double-blinded, placebo-controlled study aims to evaluate patient-reported outcomes after 36 months of treatment, with secondary measures including the 10-meter walk-run test and whole blood sorbitol levels. However, the trial's status remains "not yet recruiting," with an estimated start date in October 2025.

Clinical Setbacks and Regulatory Challenges

Applied Therapeutics has faced significant hurdles in its drug development efforts. In May 2025, govorestat failed to meet its primary endpoint in a phase 2/3 trial for CMT-SORD, failing to improve scores in a 10-meter walk-run test at 12 months compared to placebo. The company has since pivoted to focus on secondary endpoints, including statistically significant improvements in patient-reported outcomes and reduced blood sorbitol levels.

These challenges extend beyond CMT-SORD. In December 2024, the FDA rejected a new drug application for govorestat in children with classic galactosemia. This rejection was accompanied by a reprimand for data handling issues, including the deletion of electronic data by a third-party vendor and mismanagement of a dosing error.

Financial Pressures and Leadership Changes

The ongoing uncertainty surrounding govorestat's development has placed Applied Therapeutics under significant financial strain. As of June 30, 2025, the company reported cash reserves of just $30.4 million. This limited runway has raised concerns among analysts about the company's ability to fund continued development efforts.

In the wake of regulatory setbacks, Applied Therapeutics has also undergone leadership changes. Following the FDA's rejection of govorestat for galactosemia in December 2024, CEO Shoshana Shendelman, Ph.D., departed the company. Chief Financial Officer Les Funtleyder stepped in as interim CEO, tasked with navigating the company through its current challenges.

The pharmaceutical industry continues to grapple with the complexities of rare disease drug development, as exemplified by Applied Therapeutics' ongoing struggles with govorestat. As the company awaits further guidance from the FDA, stakeholders remain watchful for any signs of progress in this challenging therapeutic area.