FDA Rejects Daiichi's Lung Cancer ADC in Merck Partnership Blow

In a significant development for the HER3-targeted treatment field, the FDA has rejected Daiichi Sankyo and Merck & Co.'s antibody-drug conjugate (ADC), patritumab deruxtecan. This decision comes shortly after another setback in the HER3 domain, where BioNTech faced a partial clinical hold on its HER3-targeted ADC, BNT326.

Patritumab deruxtecan, also known as HER3-DXd, was under FDA evaluation for treatment of EGFR-mutated non-small cell lung cancer (NSCLC) after patients had undergone at least two systemic therapies. The rejection came as a surprise since the drug was expected to be the first HER3-directed medicine to hit the market, as well as Merck's inaugural ADC launch.

The FDA's complete response letter pinpointed issues encountered during an inspection of a contractor's manufacturing facility. These issues did not pertain to the drug’s efficacy or safety data, but the specifics of the production problems and the contractor’s identity were not disclosed. Daiichi Sankyo’s R&D Chief, Ken Takeshita, M.D., emphasized the company's commitment to resolving the feedback swiftly in collaboration with Merck and the third-party manufacturer.

The FDA's decision dealt a blow to Merck and Daiichi's plans, especially given the context that patritumab deruxtecan led to a tumor shrinkage rate of 29.8% in the pivotal HERTHENA-Lung01 trial. The median duration of response among the EGFR-mutated NSCLC patients was 6.4 months. However, there were safety concerns; among the 225 trial participants, one death due to interstitial lung disease—a known side effect of Daiichi’s DXd technology—was reported.

Besides the HERTHENA-Lung01 study, Daiichi Sankyo is also conducting the phase 3 HERTHENA-Lung02 trial. This study aims to compare patritumab deruxtecan against platinum-based chemotherapy as a second-line therapy following the failure of an EGFR tyrosine kinase inhibitor (TKI). The drug is also being evaluated for potential use in breast cancer treatment.

Under their $4 billion upfront deal, Merck and Daiichi are co-developing and co-commercializing three ADC assets, including patritumab deruxtecan. The other two assets target B7-H3 and CDH6, respectively. Patritumab deruxtecan represents the most advanced candidate in this partnership, bringing both companies closer to leading the HER3-targeted treatment market.

In light of the manufacturing issues, Merck and Daiichi Sankyo are focusing on addressing the FDA's concerns to bring patritumab deruxtecan to market. A Merck spokesperson reiterated the company's commitment to resolving these issues promptly, promising to share more information about the anticipated timeline as it becomes available.

Daiichi Sankyo has been heavily investing in its manufacturing capabilities for ADCs, starting with a 15 billion yen initiative in 2017 to enhance production lines at three of its Japanese plants. More recently, the company announced a 1 billion euro investment to expand its Pfaffenhofen site in Germany, aiming to boost production capacities for both cardiovascular drugs and ADCs.

In conclusion, while the FDA's rejection of patritumab deruxtecan poses a significant hurdle, both Daiichi Sankyo and Merck remain resolute in their efforts to address the identified manufacturing issues and bring this innovative HER3-directed treatment to patients in need.