Merck (NYSE: MRK) and Daiichi Sankyo (TYO: 4568) announced that their antibody-drug conjugate (ADC) patritumab deruxtecan (HER3-DXd) has passed Phase 3 HERTHENA-Lung 02 study, months after the drug was rejected by the U.S. FDA due to manufacturing issues following its presentation at this year’s ESMO conference. The companies will discuss the trial results with global regulatory authorities.
Patritumab deruxtecan, a potential first-in-class HER3-targeting DXd ADC designed using Daiichi Sankyo’s technology, is currently under joint development by Daiichi Sankyo and Merck. The HERTHENA-Lung 02 Phase 3 trial assessed the efficacy of patritumab deruxtecan (HER3-DXd) in patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) previously treated with EGFR tyrosine kinase inhibitors (TKIs). The trial met its primary endpoint of progression-free survival (PFS), showing a significant statistical improvement in PFS compared to platinum-based pemetrexed induction chemotherapy and subsequent pemetrexed maintenance therapy. At the time of analysis, overall survival (OS) data were immature, and the trial will continue to evaluate the secondary endpoint of OS.
The safety profile of HERTHENA-Lung 02 was consistent with previous lung cancer clinical trials, with no new safety signals identified. Most interstitial lung disease (ILD) events were mild (Grade 1 and 2). Two Grade 5 ILD events (fatal) were observed, following a single Grade 5 ILD case in its Phase 2 study.
This collaboration began in October 2023 when Daiichi Sankyo and Merck entered into a global development and commercialization agreement for three of Daiichi Sankyo’s ADC candidates: patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd), and raludotatug deruxtecan (R-DXd), with Daiichi Sankyo retaining exclusive rights in Japan and being fully responsible for product manufacturing and supply.
Under the agreement, Merck will pay Daiichi Sankyo a $1.5 billion upfront payment for the ifinatamab deruxtecan project, with the same upfront payment for the patritumab deruxtecan and raludotatug deruxtecan projects. Merck will also pay additional $5.5 billion in milestone payments for each project based on certain sales milestones, making the potential total value of the three projects up to $22 billion.
On August 6, 2024, Daiichi Sankyo and Merck expanded their existing global co-development and co-commercialization agreement for three investigational DXd ADCs to include Merck’s MK-6070, a delta-like ligand 3 (DLL3) targeted T-cell engager acquired by Merck for approximately $680 million through the acquisition of Harpoon Therapeutics.
Under the agreement, Merck will receive a $170 million upfront payment and a royalty on sales. Both companies will co-develop and co-commercialize MK-6070 globally (excluding Japan), with Merck retaining exclusive rights in Japan. Merck will be responsible for the production and supply of MK-6070 and will book global sales of the product. R&D costs associated with the combination use of MK-6070 and ifinatamab deruxtecan will be shared according to the original agreement for ifinatmab deruxtecan.
On June 26 of this year, the FDA refused to approve the Biologics License Application (BLA) for accelerated approval of patritumab deruxtecan (HER3-DXd) submitted by Daiichi Sankyo and Merck, citing issues found during an inspection of a third-party manufacturing facility, without pointing to any efficacy or safety issues with the data submitted in the application. Daiichi Sankyo stated it would work closely with the FDA and the third-party manufacturer to address the feedback as soon as possible. – Flcube.com
