FDA Rejects Applied Therapeutics' Govorestat for Galactosemia, Citing Clinical Application Deficiencies
核心洞察
The FDA has rejected Applied Therapeutics' marketing application for govorestat for the treatment of galactosaemia (搜索) due to deficiencies in the clinical application.
The agency also issued a warning letter regarding a clinical trial of govorestat, citing issues with electronic data capture and access to records.
Applied Therapeutics plans to request a meeting with the FDA to discuss requirements for potential resubmission or appeal of the decision.
Applied Therapeutics' shares plummeted after the FDA rejected its marketing application for govorestat (formerly AT007) for the treatment of galactosaemia (搜索), citing "deficiencies in the clinical application." The company is also facing scrutiny after receiving a warning letter from the FDA regarding a clinical trial of the same drug.
FDA Rejection and Concerns
The FDA's decision to reject govorestat comes after an extended review period to consider additional data. Applied Therapeutics is currently reviewing the complete response letter (CRL) and intends to request a meeting with the FDA to discuss potential next steps, including resubmission or appeal options. The Galactosemia Foundation expressed disappointment, calling the outcome "devastating" for patients and families.
Warning Letter Details
In addition to the rejection, Applied Therapeutics received a warning letter from the FDA citing "objectionable conditions" observed during an inspection of the AT-007-1002 clinical trial. The issues raised primarily concern electronic data capture (EDC) problems and a failure to provide the FDA with access to necessary records. Applied Therapeutics stated that it believes these issues were addressed in prior communications with the agency, including the provision of detailed paper and video records.
The warning letter also mentioned a dosing error during the dose-escalation phase of the study, which resulted in slightly lower levels than targeted in a limited number of patients. The company stated that this issue was "remedied prior to achieving maintenance dosing."
Govorestat and Galactosemia
Galactosemia is a rare inherited metabolic disorder affecting approximately 3,000 patients in the US, with 80 new births each year. It is caused by a defect in the body's ability to process galactose, a sugar found in milk, leading to the buildup of harmful metabolites. Currently, the condition is managed through dietary restrictions, which can be challenging. Govorestat is an aldose reductase (搜索) inhibitor (ARI) designed to restore the ability to metabolize galactose.
Future Plans
Despite the setback with galactosaemia (搜索), Applied Therapeutics is still developing govorestat for the treatment of sorbitol dehydrogenase (SORD) deficiency, a rare and progressive neuromuscular disease. The company hopes to file for approval in that indication in the first quarter of 2025.