默沙东又踩了个雷

Core Viewpoint - The clinical trial for the B7-H3 ADC drug I-Dxd, developed by Merck and Daiichi Sankyo, has been globally suspended due to a higher-than-expected incidence of grade 5 interstitial lung disease (ILD), which corresponds to fatal outcomes in medical toxicity grading [1][2]. Group 1: Clinical Trial Outcomes - The suspension of the I-Dxd trial represents a significant setback for a $22 billion ADC collaboration project between Merck and Daiichi Sankyo, which had high expectations [2]. - Prior to this, another ADC, Patritumab deruxtecan, was withdrawn from the market due to poor overall survival data, with two patient deaths attributed to ILD during clinical trials [2][3]. - The increasing occurrence of severe ILD has led to a decrease in regulatory tolerance for ADCs, raising concerns about the safety of these therapies [3][7]. Group 2: ADC Safety Concerns - The FDA has begun to scrutinize ADC safety more closely, particularly in light of the recent clinical trial suspensions and the associated fatal adverse reactions [5][16]. - Previous studies indicated that I-Dxd had already shown ILD signals in earlier phases, with 36.5% of patients experiencing grade 3 or higher treatment-related adverse events (TRAEs) in the IDeate-Lung01 trial [5]. - The safety issues surrounding ILD are not isolated to a single drug or design but may be inherent risks associated with the Dxd toxin platform [10][11]. Group 3: Market Implications - Despite the safety concerns, ADCs remain a critical technology in oncology, capable of significantly improving efficacy in late-stage patients [14][15]. - The recent approval of Enhertu for a new indication demonstrates that regulatory bodies may allow for some flexibility in safety standards if the therapeutic benefits are substantial [15][16]. - The competitive landscape for ADCs is shifting, with a growing emphasis on balancing efficacy and safety, particularly in managing systemic exposure to minimize damage to normal cells [16].