FDA Says It Won’t Approve Applied Therapeutics’ Drug for Rare Metabolic Disorder

Rare Daily Staff

The U.S. Food and Drug Administration notified Applied Therapeutics that it would not approve its application to market its experimental drug govorestat for the treatment of the rare metabolic disorder classic galactosemia because of deficiencies in the clinical application.

The news sent shares of the company down about 80 percent.

Applied Therapeutics said it is reviewing the feedback from the agency and plans to request a meeting to discuss requirements for a potential resubmission of its application or appeal the decision along with appropriate next steps.

“Galactosemia is a progressive and debilitating disease without any existing treatment options and there remains a high unmet medical need for this community,” said Shoshana Shendelman, founder and CEO of Applied Therapeutics. “As we move forward, we plan to work with the FDA to address the concerns in the [complete response letter] and determine an expeditious path to bring this much needed treatment to patients.”

Galactosemia results in an inability to metabolize the simple sugar galactose. Galactose is found in foods but is also produced endogenously by the body. When not metabolized properly, galactose is converted to the toxic metabolite, galactitol, which causes neurological complications, including deficiencies in cognition, behavior, activities of daily living, adaptive skills, fine and gross motor skills and speech, as well as tremor and seizures. Newborn screening for Galactosemia is mandatory in the U.S. and most E.U. countries.

Govorestat is a central nervous system penetrant aldose reductase inhibitor being developed for the treatment of multiple rare diseases.

Govorestat has received Orphan Medicinal Product Designation from the European Medicines Agency for both Galactosemia and SORD Deficiency. Govorestat has also received Orphan Drug designation from the FDA for the treatment of galactosemia, PMM2- congenital disorder of glycosylation, and SORD deficiency; Pediatric Rare Disease designation for galactosemia and PMM2-CDG; and Fast Track designation for galactosemia.

The company said govorestat has demonstrated rapid and sustained reductions in galactitol in clinical trials, which resulted in a meaningful benefit on clinical outcomes across pediatric patients, alongside a favorable safety profile. In the phase 3 registrational ACTION-Galactosemia Kids study in children with Galactosemia aged 2 to17, treatment with govorestat demonstrated clinical benefit on activities of daily living, behavioral symptoms, cognition, fine motor skills and tremor.

Govorestat also significantly reduced plasma galactitol levels in both adults and children with Galactosemia. Additional supportive studies resulted in robust efficacy and safety data across 185 patients with classic galactosemia over three years.

Govorestat is also being developed for the treatment of sorbitol dehydrogenase (SORD) deficiency, a rare and progressive neuromuscular disease. The company expects to submit a new drug application early in the first quarter of 2025. The review and potential approval of govorestat for the treatment of SORD is independent of the ongoing review of govorestat for classic galactosemia.

Photo: Shoshana Shendelman, founder and CEO of Applied Therapeutics