Daiichi Sankyo and Merck Withdraw HER3-DXd FDA Filing Amid Clinical Trial Setback

Daiichi Sankyo and Merck & Co. have voluntarily withdrawn their Biologics License Application (BLA) for patritumab deruxtecan (HER3-DXd) from the U.S. Food and Drug Administration (FDA). This decision comes after a phase 3 confirmatory trial failed to meet its overall survival endpoint, dealing a significant blow to the companies' ambitions in the non-small cell lung cancer (NSCLC) treatment landscape.

Trial Results Fall Short of Expectations

The HERTHENA-Lung02 trial, a phase 3 study evaluating HER3-DXd as a monotherapy against doublet chemotherapy in patients with EGFR-mutated, advanced NSCLC, did not achieve statistical significance in overall survival. This outcome was revealed in topline results set to be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

According to data released on the ASCO website, the trial showed a mere 0.4-month improvement in progression-free survival (PFS). Additionally, two deaths due to interstitial lung disease were reported in the HER3-DXd arm, raising safety concerns.

Regulatory Challenges and Manufacturing Issues

This withdrawal marks the second major setback for HER3-DXd in recent years. In June 2024, the FDA issued a Complete Response Letter (CRL) for the drug, citing issues with a third-party manufacturing facility. At that time, the regulatory body did not raise concerns about the clinical data submitted.

The initial BLA was based on promising results from the phase 2 HERTHENA-Lung01 study, which demonstrated an objective response rate of 29.8% in 225 patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on previous treatments.

Impact on Merck-Daiichi Collaboration

HER3-DXd is one of three antibody-drug conjugates (ADCs) included in a substantial $4 billion upfront deal between Merck and Daiichi Sankyo, signed in the fall of 2023. At the time of the agreement, HER3-DXd was considered the most advanced asset in the collaboration, with high expectations for near-term market entry.

Despite this setback, both companies have expressed continued interest in developing the drug. Ken Takeshita, M.D., Daiichi's global head of R&D, stated, "We remain confident in the broad development program of this HER3-directed antibody drug conjugate, which currently includes multiple clinical trials across 15 types of cancer."

As the pharmaceutical industry closely watches the evolving landscape of targeted cancer therapies, the future of HER3-DXd and similar ADCs remains a subject of intense interest and scrutiny.