Regulatory Setback For Applied Therapeutics' Lead Program, FDA Highlights Deficiencies In Clinical Application

On Wednesday, Applied Therapeutics, Inc APLT received an FDA Complete Response Letter (CRL) for the New Drug Application (NDA) for govorestat for Classic Galactosemia.

Galactosemia is a rare genetic metabolic disease resulting in an inability to metabolize the simple sugar galactose. When not appropriately metabolized, galactose is converted to the toxic metabolite, galactitol, which causes neurological complications.

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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 FDA feedback. It plans to immediately request a meeting to discuss the requirements for a potential resubmission of the NDA or appeal of the decision and appropriate next steps.

In 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 adults and children with Galactosemia.

Govorestat is also being developed for Sorbitol Dehydrogenase (SORD) Deficiency, a rare and progressive neuromuscular disease. The company expects to submit an NDA early in the first quarter of 2025.

William Blair stated that they were confident in the approval of govorestat ahead of its PDUFA date, given strong clinical data showing its effectiveness for a rare disease with no available treatments. However, the FDA’s rejection was unexpected and disappointing.

With limited details in the CRL, the next steps for govorestat in treating galactosemia remain unclear, including whether another clinical trial will be required.

As a result, William Blair has lowered its probability of success for the galactosemia program to 30% and delayed the projected U.S. launch to the fourth quarter of 2025, pending further clarification.

Despite this setback, William Blair maintained its Outperform rating, noting that the CRL likely doesn’t impact the company’s other program targeting SORD.

They emphasized that the SORD clinical trial met its key goals and offered a stronger data package. Additionally, the FDA’s alignment on an accelerated approval pathway for SORD suggests that, if granted priority review, govorestat could still begin generating revenue by late 2025.

Price Action: APLT stock is down 67.2% at $2.81 during the premarket session at last check Friday.

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