恒瑞医药上岸，但TGF-β还没有

Core Viewpoint - The successful launch of SHR-1701 (Rilafurpu-α) by Heng Rui Medicine marks a significant achievement in the PD-L1/TGF-β dual antibody field, especially as it becomes the first globally approved drug targeting this pathway, showcasing the company's strong clinical design and regulatory communication skills [1][2]. Group 1: Product Approval and Market Context - Rilafurpu-α was officially approved by the NMPA on January 7, indicated for use in combination with fluorouracil and platinum-based drugs for first-line treatment of locally advanced, unresectable, recurrent, or metastatic gastric and gastroesophageal junction adenocarcinoma [1]. - The clinical trial design for Rilafurpu-α involved a treatment group receiving the drug combined with chemotherapy and a control group receiving a placebo with chemotherapy, raising questions about the validity of its success [1][12]. - In the current landscape of first-line gastric cancer treatment, immune checkpoint inhibitors combined with chemotherapy have become standard for HER2-negative patients, with several PD-(L)1 inhibitors already recommended in global guidelines [1][10]. Group 2: Competitive Landscape and Challenges - Despite the approval, Rilafurpu-α has not demonstrated clear efficacy and safety advantages over existing PD-(L)1 inhibitors, leading to uncertainty regarding its market prospects [2][12]. - The failures of Merck's PD-L1/TGF-β dual antibody M7824 in multiple clinical trials have cast doubt on the effectiveness of TGF-β as a target, although it has not completely discredited the potential of the dual mechanism [5][6][7]. - Heng Rui's clinical design strategy, which included stratifying patients based on PD-L1 expression and other factors, contrasts with Merck's more generalized approach, potentially providing a clearer assessment of Rilafurpu-α's efficacy [9][10]. Group 3: Unresolved Questions - The approval of Rilafurpu-α raises critical questions about whether its clinical success is due to the PD-L1 pathway or the synergistic effects of TGF-β [10][14]. - Comparisons with existing PD-1 therapies indicate that Rilafurpu-α may not offer a competitive advantage, especially as prices for PD-1 drugs have significantly decreased [12][14]. - The ongoing exploration of TGF-β mechanisms and the positioning of Rilafurpu-α in the treatment landscape remain areas for further investigation by Heng Rui and other companies [14].