Applied Therapeutics is under increased scrutiny after the FDA issued a Warning Letter in November 2024 following a preapproval bioresearch monitoring (BIMO) inspection. The inspection revealed critical data integrity issues in the AT-007-1002 trial (ACTION-Galactosemia Kids trial) of govorestat, a drug candidate for treating galactosemia in children aged 2-17. These events have led to shareholder lawsuits and leadership changes within the company.
The FDA's BIMO program aims to ensure the integrity of data submitted and protect research participants. The inspection uncovered Good Clinical Practice (GCP) compliance issues, specifically a dosing error during the dose escalation phase of the ACTION-Galactosemia Kids trial.
Details of the FDA Findings
The FDA's Warning Letter highlighted significant protocol deviations. During the dose-escalation phase of the AT-007-1002 trial, at least 19 patients at one clinical site received doses approximately 80% lower than specified in the protocol between March and June 2021 due to mislabeled product. Applied Therapeutics reported the incorrect, higher dose in the protocol rather than the actual administered dose. The FDA stated the company failed to provide a description or analysis of the dosing errors, raising concerns about the validity and reliability of the data.
Further complicating matters, a third-party vendor deleted electronic records, including audit trails, for all 47 study participants in the AT-007-1002 trial shortly after the FDA preannounced its inspection. This deletion included electronic clinical outcome assessments used for measuring primary and secondary efficacy endpoints, preventing the FDA from accessing and verifying critical data.
Legal and Leadership Repercussions
Following the FDA's actions, shareholders filed lawsuits against Applied Therapeutics in December 2024, alleging the company failed to disclose risks related to govorestat's approval and misled investors. The lawsuits claim the company did not reveal the dosing error or vendor data deletion issues while continuing to issue positive press releases about govorestat. These suits seek to represent investors who purchased Applied Therapeutics’ securities between January 3, 2024, and December 2, 2024.
Amidst these challenges, Applied Therapeutics announced the resignation of its founder and CEO, Dr. Shoshana Shendelman, on December 20, 2024.
Implications for Clinical Trial Sponsors
These events highlight the FDA's focus on data integrity and clinical trial conduct. Sponsors should proactively disclose risks, provide timely updates on material developments, establish robust internal controls over third-party vendors, and cooperate with regulators during inspections. Companies should ensure they can provide regulators access to records and reports related to clinical investigations.
