Merck's Phase 3 trial results indicate that a subcutaneous formulation of pembrolizumab (Keytruda), co-administered with berahyaluronidase alfa, is as effective as the intravenous (IV) form in treating metastatic non-small cell lung cancer (NSCLC). This new delivery method could offer a more convenient option for patients, potentially impacting Keytruda's market longevity as its exclusivity nears expiration.
Phase 3 Trial Demonstrates Non-Inferiority of Subcutaneous Keytruda
The randomized, open-label Phase 3 MK-3475A-D77 trial (NCT05722015) compared subcutaneous Keytruda with berahyaluronidase alfa to IV Keytruda, both in combination with chemotherapy, as a first-line treatment for metastatic NSCLC. The study's primary endpoint was met, demonstrating that the subcutaneous formulation, administered every six weeks, is non-inferior to the IV formulation. The trial also achieved its safety and efficacy goals, supporting the potential of this alternative delivery method.
Strategic Implications for Merck Amidst Patent Expiry
Keytruda, approved in 2014, has significantly improved outcomes for cancer patients by leveraging the body's immune system. In advanced lung cancer, Keytruda has contributed to a five-year survival rate of approximately 25%, a substantial increase from the historical rate of 5%. With Keytruda's exclusivity set to expire in 2028, Merck is exploring strategies to maintain its market position. Analysts suggest that the positive Phase 3 results for the subcutaneous formulation could delay the shift to biosimilars, as expanding indications for this version may bolster Keytruda's overall market presence. The convenience of subcutaneous administration could appeal to patients and physicians, particularly in regions with limited access to infusion centers.
Merck estimates that up to 50% of patients could eventually benefit from the subcutaneous formulation, potentially broadening Keytruda's accessibility. The company is further evaluating this formulation in additional trials, including a Phase III study for first-line NSCLC patients and Phase II studies for relapsed or refractory Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma.
Addressing Biosimilar Competition and Pricing Strategies
Several companies, including Sandoz, Samsung Bioepis, Amgen, and Celltrion, are developing biosimilar versions of pembrolizumab. Merck aims to secure approval for the subcutaneous version to facilitate a transition before the 2028 patent expiration. The subcutaneous formulation, combining Keytruda's active ingredient with Alteogen's enzyme for enhanced absorption, is protected by new patents and offers a more convenient administration compared to the current 30-minute infusion.
Moreover, subcutaneous Keytruda could provide a pricing advantage. According to recent guidance from the Centers for Medicare and Medicaid Services (CMS), the subcutaneous version may be treated as a separate drug due to the inclusion of berahyaluronidase alfa, potentially allowing Merck to continue setting its own prices for this formulation. This strategic move could help Merck retain pricing power for subcutaneous Keytruda, even as the original Keytruda's price decreases for Medicare patients after 2028.
