Applied Therapeutics: Navigating the FDA's Feedback

Applied Therapeutics, a biopharmaceutical company with a pipeline of novel drug candidates, finds itself at a critical juncture following the U.S. Food and Drug Administration's (FDA) issuance of a Complete Response Letter (CRL) for its New Drug Application (NDA) of govorestat, an investigational drug for the treatment of Classic Galactosemia. The company is now 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.

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 disappointed by the FDA's decision but remains committed to the Galactosemia community and the development of govorestat. The company believes that the drug has the potential to change the lives of patients with Galactosemia and is determined 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.

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 2-17, 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.

Applied Therapeutics' path forward hinges on addressing FDA concerns. Key steps include clarifying the exact deficiencies in the clinical application, understanding the FDA's specific concerns, and addressing them explicitly. The company should also re-evaluate or add studies to enhance the robustness of clinical data, ensure a strong safety profile, and engage stakeholders, such as Galactosemia patients, families, and healthcare providers, to gather insights and build consensus. By focusing on these aspects, Applied Therapeutics can enhance its chances of NDA approval.

The FDA's feedback may also influence the company's development plans for govorestat and other drug candidates. If the issues are resolvable, a resubmission could be feasible, potentially salvaging the drug's commercial prospects. However, if the concerns are irremediable, an appeal or pivot to other indications may be necessary. Meanwhile, the setback with govorestat might prompt the company to accelerate development of its other drug candidates, like AT-001, to diversify its pipeline and mitigate risk.

Applied Therapeutics' subsequent steps for govorestat hinge on the specifics of the FDA's feedback. If the issues are resolvable, a resubmission could be feasible, potentially salvaging the drug's commercial prospects. However, if the concerns are irremediable, an appeal or pivot to other indications may be necessary. Meanwhile, the setback with govorestat might prompt the company to accelerate development of its other drug candidates, like AT-001, to diversify its pipeline and mitigate risk.

Ultimately, the success of Applied Therapeutics' efforts to address the FDA's concerns will determine the fate of govorestat and the company's future in the rare disease therapeutic landscape. By remaining committed to the Galactosemia community and diligently working with the FDA, Applied Therapeutics has the opportunity to bring a transformative treatment to patients in need.