Warning letter adds to Applied Tx run of bad news

Applied Therapeutics has been sent a warning letter from the FDA over a clinical trial of its rare disease therapy govorestat, which was rejected by the agency last week.

The letter – addressed to Applied's chief executive, Shoshana Shendelman – cites "objectionable conditions" observed in an FDA inspection carried out earlier this year that the regulator believes violate its regulations.

Among the issues detailed in a Form 483 notice issued by the agency was a failure to allow an FDA official access to records generated in the AT-007-1002 clinical trial that was central to the company's marketing application for govorestat, as well as other data related to the study. The company's response to the notice was not deemed adequate, so the FDA moved ahead with a warning letter.

In a regulatory filing, Applied said that the issues raised by the regulator mainly related to problems with electronic data capture (EDC) in the trial, adding that it "believes [these] were addressed in prior communications with the agency, including by providing detailed paper and video records."

The warning letter also refers to a dosing error in the dose-escalation phase of the study, resulting in slightly lower levels than targeted in a limited number of patients, which the company said was "remedied prior to achieving maintenance dosing."

The inspection took place several months before govorestat was turned down as a treatment for the rare genetic disorder galactosaemia, wreaking havoc on Applied's share price, which also fell after news of the warning letter emerged.

The company asserted that detailed records were maintained and information was provided to the FDA, adding that it intends to respond within the permitted 15 business days to address the issues.

The govorestat verdict came after the FDA had extended its review of the drug to consider additional data from the company to support the application. The decision not to approve the drug was met with consternation by the Galactosemia Foundation, which represents patients with the disorder, and which called the outcome "devastating."

There are no approved drugs to treat the disorder, which affects approximately 3,000 patients in the US and 80 new births each year. It is caused by a defect in the ability to process galactose, a sugar found in milk, causing harmful metabolites to build up in the body.

At the moment, the rare disease can only be managed by restricting galactose from the diet, which can be challenging as many food products contain milk-based ingredients.

Photo by Kate Macate on Unsplash