Complete Response Letter for govorestat for the treatment of classic galactosemia

The CRL indicates that the FDA completed its review of the application and determined that it is unable to approve the NDA in its current form, citing deficiencies in the clinical application.

Applied Therapeutics is reviewing the feedback from the FDA and plans to immediately request a meeting to discuss requirements for a potential resubmission of the NDA or appeal of the decision along with appropriate next steps. “We are disappointed by the FDA’s decision . Our strong commitment to the Galactosemia community is rooted in our belief that govorestat has the potential to change the lives of patients with Galactosemia, which we believe is evidenced by the breadth of efficacy and safety data demonstrating its ability to stop the decline on progressive clinical outcomes, including cognition and behavior,” said Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics. “Galactosemia is a progressive and debilitating disease without any existing treatment options and there remains a high unmet medical need for this community. As we move forward, we plan to work with the FDA to address the concerns in the CRL and determine an expeditious path to bring this much needed treatment to patients. We are grateful to the patients, families, and healthcare providers who participated in the govorestat clinical studies.”

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 III registrational ACTION-Galactosemia Kids study in children with Galactosemia aged 2-17, 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 3 years. The results of the ACTION-Galactosemia Kids study and the Phase 1/2 ACTION-Galactosemia study in adult patients with Galactosemia were published in the Journal of Clinical Pharmacology.

Govorestat is also being developed for the treatment of Sorbitol Dehydrogenase (SORD) Deficiency, a rare and progressive neuromuscular disease. The Company expects to submit an NDA 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.

 Citation: Results of the  Action  Galactosemia -KIDS Study to Evaluate the Effects of  Govorestat in Pediatric Patients with Classic Galactosemia; Evan Bailey MD, Han Phan MD, Ayesha Ahmad MD, Janet Thomas MD, Elizabeth G. Ames MD, Amanda B. Pritchard MD, Shane C. Quinonez MD, Stella Wang MS, MPH, Caleb Dayley MS, Andrew Salt MS, Christina Pick MS, Abe Durrant MS, Samuel Johnson MS, Jessie Nicodemus-Johnson PhD, Samuel P. Dickson PhD, Riccardo Perfetti MD, PhD, Suzanne B. Hendrix PhD, Shoshana Shendelman PhD. The Journal of Clinical Pharmacology. First published: 21 November 2024,