Merck Halts TIGIT/LAG-3 Project, Shifts Focus to $2 Billion Oral GLP-1 Drug Collaboration

On December 16, Merck announced on its official website that it has officially stopped the development of the anti-TIGIT antibody Vibostolimab and the anti-LAG-3 antibody Favezelimab. This decision marks the end of Merck's years of effort in the field of immune checkpoint inhibitors. Two days later, on December 18, Merck announced its new strategic direction by reaching a collaboration agreement with domestic company Hansoh Pharmaceutical. According to the agreement, Merck will obtain global exclusive licensing rights for Hansoh’s oral small molecule GLP-1 receptor agonist HS-10535, while Hansoh will retain control of the drug in the Chinese market. The total amount of this collaboration is as high as $2 billion.

This series of business adjustments reflects Merck's concerns about the impending patent cliff for its main product, Pembrolizumab (Keytruda). At the same time, these adjustments provide clues about future competitive focuses for innovative pharmaceutical companies.

Vibostolimab, which Merck has discontinued, is an antibody drug targeting the TIGIT site. TIGIT is an inhibitory receptor expressed on T cells and NK cells, belonging to the immunoglobulin superfamily. Vibostolimab aims to block the TIGIT signaling pathway to enhance the body's immune response against tumor cells. Although TIGIT is regarded as a potential therapeutic target, Merck and several other pharmaceutical companies like Roche have conducted long-term development in this area but have not achieved success. Vibostolimab faced failures in multiple clinical trials, including the KeyVibe-002 trial in patients with metastatic non-small cell lung cancer (NSCLC) and studies in high-risk melanoma patients.

Similarly, Merck's other drug Favezelimab is an antibody drug targeting the LAG-3 site, aiming to restore the effector function of T cells. Despite several clinical studies, including the Phase III KEYFORM-007 study in PD-L1 positive microsatellite stable (MSS) metastatic colorectal cancer (mCRC) patients, Favezelimab also failed to meet its primary endpoint, leading Merck to decide to terminate its clinical development program.

After abandoning Vibostolimab and Favezelimab, Merck's next research focus shifts to the oral small molecule GLP-1 receptor agonist HS-10535. GLP-1 related products, as weight loss drugs, hold significant appeal for pharmaceutical companies. Novo Nordisk and Eli Lilly have already reaped substantial profits from their GLP-1 products. Merck began its layout in the GLP-1 project back in 2010, but has yet to successfully launch a product. This collaboration with Hansoh Pharmaceuticals may provide Merck with an opportunity to break through in this field.

Currently, the oral Semaglutide tablet (Rybelsus) is the only marketed oral GLP-1 drug, utilizing SNAC technology to facilitate transcellular absorption through the gastric mucosa. Eli Lilly’s Orforglipron is leading the field of oral GLP-1 receptor agonists, while domestic companies such as Heng Rui Medicine's HRS-7535 and Wenshan Medicine's VCT220 are also actively developing.

With the impending expiration of the Keytruda patent, Merck is under pressure to find its next blockbuster. Despite setbacks in the research of TIGIT, LAG-3, and GLP-1 targets, Merck's bet on oral GLP-1 small molecule drugs may provide it with a chance to overtake competitors.