The agency’s warning letter outlines Applied Therapeutics’ failure to provide adequate information regarding the clinical trial—including a dosing error for govorestat—claims that the company said it had already addressed.
Just days after failing to secure approval for govorestat in galactosemia, Applied Therapeutics on Monday announced that it had received a warning letter from the FDA over “issues” regarding the biotech’s conduct of a clinical trial for the drug candidate.
The regulator raised concerns “related to electronic data capture,” according to Applied Therapeutics’ SEC filing. The FDA on Tuesday also made public the warning letter, which pointed to “objectionable conditions” and “significant findings” documented during an inspection conducted between April 29 and May 3, 2024.
The FDA’s investigators flagged the company’s failure to allow an authorized FDA officer to access, copy and verify its records regarding the clinical trial and its conduct. The regulator further said that Applied Therapeutics did not provide a “description and analysis of any other data or information relevant to an evaluation of the safety and effectiveness” of govorestat.
The warning letter also identified a dosing error that resulted in at least 19 patients at one trial site receiving a lower dose of the study drug than called for in the protocol. Applied Therapeutics then failed to give the FDA information “describing the nature and extent of the dosing errors.” The company reported doses as stated in the protocol “rather than the actual dose levels administered,” the regulator noted in its letter.
“It appears that Applied Therapeutics did not adhere to the applicable statutory requirements in the Federal Food, Drug and Cosmetic Act and applicable regulations,” the warning letter reads.
Applied Therapeutics in its SEC filing maintained that these issues had already been “addressed in prior communications with the agency.”
“Detailed records were maintained by the Company under FDA regulatory requirements, and this information was provided to FDA,” the biotech wrote. Applied Therapeutics said it intends to respond to the regulator in the next 15 business days, as stipulated by the warning letter.
Govorestat is a brain-penetrant small molecule drug candidate that works by targeting and blocking the action of the aldose reductase enzyme, preventing the conversion of galactose to the toxic metabolite galactitol. In galactosemia—which affects around 3,000 patients in the U.S.—galactose is improperly and insufficiently broken down, leading to the accumulation of galactitol, which damages the nervous system.
Galatcosemia symptoms include behavioral, motor and cognitive problems. There are currently no approved treatments for this disease.
In rejecting govorestat for galactosemia, the FDA cited deficiencies in Applied Therapeutics’ drug application. The company plans to engage the regulator regarding the rejection to identify the best path forward for govorestat.
