MSD has announced the discontinuation of two major immunotherapy programs, dealing a significant blow to its oncology pipeline. The company is terminating the development of both its anti-TIGIT antibody vibostolimab and anti-LAG-3 antibody favezelimab, following comprehensive safety and efficacy evaluations.
Key Trial Terminations
The decision affects multiple clinical trials, including two phase 3 studies (KeyVibe-003 and KeyVibe-007) investigating vibostolimab in combination with Keytruda (pembrolizumab) for non-small cell lung cancer (NSCLC). The independent data monitoring committee recommended shutting down these trials after reviewing the complete safety and efficacy data. Additionally, the KeyVibe-006 trial in locally advanced NSCLC will also be discontinued.
For the LAG-3 program, the company is halting the KEYFORM-008 study in classical Hodgkin lymphoma, though current participants will complete their treatment course. This follows the earlier setback in September when the Keytruda-favezelimab combination failed to improve overall survival in the KEYFORM-007 trial for PD-L1-positive microsatellite stable metastatic colorectal cancer.
Industry Context and Implications
This development highlights the ongoing challenges in the checkpoint inhibitor landscape. The TIGIT pathway, in particular, has proved challenging across the industry, with several companies experiencing disappointing results. Competitors including Roche's tiragolumab and Gilead/Arcus' domvanalimab remain in late-stage testing, though the field has seen consistent setbacks.
In the LAG-3 space, Bristol-Myers Squibb's Opdualag (nivolumab + relatlimab) stands as the only approved therapy, specifically for melanoma. However, even this combination faced challenges, failing in a phase 3 trial for microsatellite stable colorectal cancer last year.
Strategic Considerations
The termination of these programs is particularly significant for MSD as it approaches the patent expiration of its blockbuster drug Keytruda, which generates approximately $25 billion annually, in 2028. Dr. Marjorie Green, head of oncology development at Merck Research Laboratories, stated that the decision to discontinue these candidates was made to "prioritize other ongoing programs" following careful data analysis.
The setback underscores the complexity of developing new checkpoint inhibitors that can effectively complement the established PD-1/PD-L1 inhibitor class, which currently dominates cancer immunotherapy. This challenge continues to shape the landscape of oncology drug development and company strategies in the immuno-oncology field.
