Merck's Keytruda Achieves Milestone with Over 38 FDA Approvals, Setting a Record for the Most Approved Indications Among Immunotherapies
Keytruda BLA 125514: Regulatory History and Expanded Approvals
Keytruda (pembrolizumab), developed by Merck & Co. (MRK), is a PD-1 (programmed cell death protein 1) immune checkpoint inhibitor. It initially received FDA approval on September 4, 2014, for the treatment of metastatic melanoma. Over the following decade, through multiple supplemental applications (sBLA), it secured approvals for over 38 solid tumor indications by 2025, making it the single immunotherapy with the most FDA approvals to date. The most recent approvals occurred in 2025 with the S-172 and S-173 supplemental approvals.
Keytruda Qlex: Strategic Shift to Subcutaneous Injection Formulation
On September 19, 2025, the FDA approved Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) subcutaneous injection formulation for 38 solid tumor indications in adult patients. Compared to the existing intravenous (IV) formulation, the subcutaneous formulation reduces administration time from 30 minutes to approximately 3-5 minutes, enhancing patient convenience. Merck CEO Rob Davis projected that 30-40% of Keytruda patients in the U.S. will switch to the subcutaneous formulation by 2027. The manufacturing process patent for this formulation is potentially protected until 2042, serving as a key defensive strategy to delay biosimilar entry even after the original patent expires in 2028.
Market Dominance and Revenue Scale
In 2025, Keytruda generated approximately $31.7 billion in annual revenue, maintaining its position as the world's top-selling prescription drug. In 2025, Q2 sales reached $7.96 billion (up 9% year-over-year), and Q3 sales reached $8.14 billion (up 10%), demonstrating consistent growth. The North American market accounts for 38.08% of total Keytruda revenue. Revenue is projected to peak at approximately $32.7 billion in 2026 before gradually declining due to patent expiration.
Competitive Landscape and Biosimilar Risk
In the global PD-1/PD-L1 inhibitor market, Keytruda's main competitors include Opdivo (nivolumab) from Bristol-Myers Squibb (BMY) (approximately $8.2 billion in revenue in 2025), Tecentriq (atezolizumab) from Roche (RHHBY), Imfinzi (durvalumab) from AstraZeneca (AZN), and Libtayo (cemiplimab) from Regeneron/Sanofi. With the U.S. patent expiring in 2028, biosimilar regulatory applications are likely to begin as early as 2026-2027. Merck is focusing on market defense through subcutaneous formulation conversion and expansion of combination therapies.
As of 2025, Keytruda is the world's top-selling prescription drug with annual revenue of $31.7 billion, accounting for approximately 50% of Merck's total revenue, representing an extremely high dependence on a single product. With the U.S. patent expiring in 2028, the strategy to extend patent protection until 2042 through the subcutaneous formulation (Keytruda Qlex) is a key variable for investors in assessing the patent cliff risk. In the overall PD-1/PD-L1 market, which exceeded $50 billion in 2025, the extensive and exclusive clinical data accumulated by Keytruda with 38 approved indications serves as a significant barrier to entry that biosimilars will find difficult to overcome. For those seeking employment in the field of immuno-oncology, understanding the sBLA supplemental application strategy, the subcutaneous formulation conversion, and the biosimilar regulatory pathway are essential areas of expertise.
Source: openFDA (api_fda)
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=BLA125514