FDA Denies Daiichi, Merck's HER3-ADC Due to Manufacturing Issues

The FDA has declined approval for Daiichi Sankyo and Merck & Co.’s HER3-targeting antibody-drug conjugate (ADC), patritumab deruxtecan, due to deficiencies found at a third-party manufacturing facility during an inspection. This setback comes less than a year after Merck committed $4 billion upfront to co-develop three ADCs from the Japanese pharmaceutical company. This isn't the first recent challenge for HER3-targeting ADCs; earlier this month, the FDA placed a partial clinical hold on an early-stage study of BioNTech's BNT326/YL202, partnered with MediLink Therapeutics, due to significant safety concerns at higher doses.

The application for patritumab deruxtecan, also known as HER3-DXd, sought accelerated approval to treat adults with locally advanced or metastatic EGFR-mutated non-small-cell lung cancer (NSCLC) who had already gone through two or more systemic therapies. This submission was supported by the pivotal Phase II HERTHENA-Lung01 study, which showed an objective response rate of nearly 30% and a median response duration of 6.4 months.

While the companies did not provide further specifics on the manufacturing issues, they clarified that the FDA's complete response letter did not question the drug’s efficacy or safety. Ken Takeshita, global head of R&D at Daiichi Sankyo, stated, “We will work closely with the FDA and the third-party manufacturer to address the feedback as quickly as possible.”

Analysts at Morgan Stanley commented that the complete response letter likely does not constitute a serious problem, predicting a delay of around 9 to 12 months, with potential approval in the first half of 2025.

Currently, Daiichi Sankyo and Merck are examining patritumab deruxtecan in the Phase III HERTHENA-Lung02 study. This trial involves patients with EGFR-mutated locally advanced or metastatic NSCLC who have experienced disease progression after treatment with a third-generation EGFR tyrosine kinase inhibitor. Additionally, other early-stage trials are investigating a variety of locally advanced or metastatic solid tumors, as well as HER3 expressing metastatic breast cancer.

Besides patritumab deruxtecan, the alliance between Daiichi Sankyo and Merck includes two other ADCs: ifinatamab deruxtecan, which targets B7-H3, and raludotatug deruxtecan, which targets CDH6. Merck aims to bolster its oncology portfolio with these assets, especially as its blockbuster cancer drug, Keytruda (pembrolizumab), faces looming patent expiration in 2028.