Daiichi Sankyo and Merck Withdraw HER3-DXd 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Daiichi Sankyo and Merck & Co. have voluntarily withdrawn their Biologics License Application (BLA) for patritumab deruxtecan (HER3-DXd) from the U.S. Food and Drug Administration (FDA). The decision comes after their phase 3 HERTHENA-Lung02 trial failed to meet its overall survival (OS) endpoint, marking another setback for the HER3-directed antibody-drug conjugate (ADC).
Trial Results Fall Short of Expectations
The HERTHENA-Lung02 study, designed to evaluate HER3-DXd as a monotherapy against doublet chemotherapy in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC), did not demonstrate statistically significant improvement in overall survival. This outcome, coupled with discussions with the FDA, led to the withdrawal of the BLA.
Detailed results from the trial, set to be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, revealed a marginal progression-free survival (PFS) improvement of just 0.4 months. 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 follows a previous setback in June 2024 when the FDA issued a complete response letter for HER3-DXd. At that time, the rejection was based on manufacturing concerns at a third-party facility rather than issues with the submitted clinical data.
The initial BLA submission was supported by promising results from the phase 2 HERTHENA-Lung01 study, which showed an objective response rate of 29.8% in 225 patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on prior treatments.
Strategic Implications for Daiichi Sankyo and Merck
Despite these challenges, both companies remain committed to the development of HER3-DXd. Ken Takeshita, M.D., Daiichi's global head of R&D, expressed confidence in the drug's broad development program, which includes multiple clinical trials across 15 types of cancer.
HER3-DXd is one of three ADC assets that Merck acquired co-development and co-commercialization rights to in a significant $4 billion upfront deal with Daiichi Sankyo in 2023. At the time of the agreement, HER3-DXd was considered the most advanced candidate among the three, highlighting the impact of this setback on the partnership's near-term prospects.
References
- Daiichi, Merck pull HER3-DXd filing at FDA after confirmatory trial misses survival endpoint
After Merck paid a hefty sum to co-develop and co-commercialize HER3-DXd, the drug has suffered notable setbacks in consecutive years.
- Daiichi, Merck pull HER3-DXd filing at FDA after confirmatory trial misses survival endpoint
After Merck paid a hefty sum to co-develop and co-commercialize HER3-DXd, the drug has suffered notable setbacks in consecutive years.
Explore Further
What specific challenges did Daiichi Sankyo and Merck face in the manufacturing process of HER3-DXd?
How does the failure of the phase 3 HERTHENA-Lung02 trial impact the strategic direction for Daiichi Sankyo's broad development program for HER3-DXd?
What are the main safety concerns associated with HER3-DXd, particularly regarding interstitial lung disease?
What impact might the withdrawal of the BLA have on the $4 billion collaboration agreement between Merck and Daiichi Sankyo?
What are the potential next steps for Daiichi Sankyo and Merck in seeking approval for HER3-DXd across the 15 cancer types included in their clinical trials?