Applied Therapeutics, Inc. (APLT) suffered a significant blow on Wednesday when the FDA issued a Complete Response Letter (CRL) for their New Drug Application (NDA) of govorestat intended to treat Classic Galactosemia. This rare genetic metabolic disorder prevents the body from properly metabolizing galactose, leading to the accumulation of the toxic metabolite galactitol, causing serious neurological complications. The CRL, while not detailing specific deficiencies, effectively halts the approval process for govorestat in its current form.
The news sent shockwaves through the market. William Blair, an investment firm that previously held a positive outlook on govorestat’s approval, citing strong Phase 3 clinical trial data demonstrating the drug’s efficacy in improving activities of daily living, behavioral symptoms, cognition, and motor skills in children aged 2-17, now expresses disappointment. The ACTION-Galactosemia Kids study also showcased govorestat’s significant reduction of plasma galactitol levels in both children and adults. This positive data made the FDA’s rejection all the more surprising.
The uncertainty surrounding the CRL’s specifics leaves many questions unanswered. Will further clinical trials be necessary? What steps will Applied Therapeutics take to address the FDA’s concerns? The company plans to meet with the FDA to discuss the CRL and determine the path forward, potentially involving a resubmission of the NDA or an appeal. William Blair has, in the interim, adjusted its probability of success for govorestat’s galactosemia program to 30% and pushed back the projected U.S. launch to the fourth quarter of 2025, pending clarification.
Despite this setback for the galactosemia program, there is a glimmer of hope. William Blair maintains its ‘Outperform’ rating for APLT, emphasizing that the CRL is unlikely to affect the company’s promising SORD program. This program focuses on Sorbitol Dehydrogenase (SORD) Deficiency, another rare and progressive neuromuscular disease. The SORD clinical trial successfully met its primary endpoints, resulting in a robust data package. Furthermore, the FDA’s openness to an accelerated approval pathway for SORD suggests a potential for govorestat to generate revenue by late 2025, should priority review be granted.
The immediate impact on APLT stock is stark: a premarket plunge of 67.2%, dropping the price to $2.81. Investors are understandably concerned about the future of govorestat for galactosemia treatment. The situation highlights the inherent risks and uncertainties associated with the pharmaceutical development process, especially for rare diseases where the need for effective treatment is immense but the regulatory hurdles can be steep. The coming weeks will be critical in determining Applied Therapeutics’ next steps and the ultimate fate of govorestat for the treatment of Galactosemia.
