Merck's Keytruda in the EU: Regulatory Momentum and Strategic Positioning in a Competitive Oncology Landscape

Merck's Keytruda has emerged as a pivotal player in the European Union's oncology market, driven by regulatory breakthroughs and strategic market access initiatives. As the European Medicines Agency (EMA) advances its review of Keytruda's subcutaneous (SC) formulation and expanded indications, investors are closely watching how these developments position the drug to maintain its competitive edge amid patent expiration risks and intensifying rivalry with rivals like Bristol-Myers Squibb's Opdivo and AstraZeneca's Imfinzi.

Regulatory Acceleration: Subcutaneous Formulation and New Indications

The EMA's Committee for Medicinal Products for Human Use (CHMP) has delivered two landmark recommendations for Keytruda in 2025. First, the agency endorsed a subcutaneous administration route for Keytruda, which reduces treatment time from hours-long intravenous infusions to just one minute every three weeks or two minutes every six weeksMerck’s $3 Billion Budget Shift: Preparing for Keytruda’s Post-Exclusivity Era and New Opportunities [https://medicinetomarket.com/mercks-3-billion-budget-shift-preparing-for-keytrudas-postexclusivity-era-and-new-opportunities/]^[1]. This formulation, approved for all existing EU indications, addresses a critical unmet need for patient convenience and healthcare system efficiencyMerck Receives Two Positive EU CHMP Opinions for KEYTRUDA (pembrolizumab) for Subcutaneous (SC) Administration and for New Indication for Earlier-Stage Head and Neck Cancer [https://www.merck.com/news/merck-receives-two-positive-eu-chmp-opinions-for-keytruda-pembrolizumab-for-subcutaneous-sc-administration-and-for-new-indication-for-earlier-stage-head-and-neck-cancer/]^[3]. Second, the CHMP recommended Keytruda as a perioperative regimen for resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC), based on the Phase 3 KEYNOTE-689 trial's demonstration of improved event-free survivalMerck Receives Two Positive EU CHMP Opinions for KEYTRUDA (pembrolizumab) for Subcutaneous (SC) Administration and for New Indication for Earlier-Stage Head and Neck Cancer [https://www.merck.com/news/merck-receives-two-positive-eu-chmp-opinions-for-keytruda-pembrolizumab-for-subcutaneous-sc-administration-and-for-new-indication-for-earlier-stage-head-and-neck-cancer/]^[3]. These approvals, pending final European Commission decisions in Q4 2025, underscore Merck's ability to leverage the EMA's PRIME and conditional approval pathways to expedite market accessEU regulators reject new use for Opdivo, as Keytruda edges ahead [https://pharmaphorum.com/news/eu-regulators-reject-new-use-for-opdivo-as-keytruda-edges-ahead]^[2].

Market Access Strategies: Pricing, Reimbursement, and R&D Rebalancing

Merck's approach to sustaining Keytruda's EU market access reflects a dual focus on mitigating patent expiration risks (expected by 2028) and addressing payer resistance to its high cost. The company has reallocated $3 billion of its budget toward R&D and newer products like Welireg, signaling a long-term strategy to diversify revenue streamsMerck’s $3 Billion Budget Shift: Preparing for Keytruda’s Post-Exclusivity Era and New Opportunities [https://medicinetomarket.com/mercks-3-billion-budget-shift-preparing-for-keytrudas-postexclusivity-era-and-new-opportunities/]^[1]. In the short term, Merck is navigating reimbursement challenges through value-based pricing agreements and patient assistance programs, which help offset Keytruda's annual cost of $150,000–$175,000 in the U.S. and similar pressures in EuropeEU regulators reject new use for Opdivo, as Keytruda edges ahead [https://pharmaphorum.com/news/eu-regulators-reject-new-use-for-opdivo-as-keytruda-edges-ahead]^[2]. Additionally, the company is investing in real-world evidence to reinforce Keytruda's cost-effectiveness in key markets, a critical tactic as the EU's Joint Committee on Health Technology Assessment (JCA) tightens reimbursement criteriaMarket Access and Reimbursement in Key European Markets and the US [https://petauri.com/insights/market-access-reimbursement-europe-us/]^[4].

Competitive Positioning: Outpacing Opdivo and Navigating Imfinzi's Expansion

Keytruda's regulatory momentum has translated into measurable market share gains. In Q3 2025, Keytruda reported EU sales of $1.67 billion, narrowly surpassing Opdivo's $1.65 billion, a shift attributed to Keytruda's recent approvals and Opdivo's regulatory setbacks, including the EMA's rejection of a first-line kidney cancer indicationEU regulators reject new use for Opdivo, as Keytruda edges ahead [https://pharmaphorum.com/news/eu-regulators-reject-new-use-for-opdivo-as-keytruda-edges-ahead]^[2]. Analysts note that Keytruda's broader label expansions—spanning melanoma, non-small cell lung cancer (NSCLC), and bladder cancer—have solidified its position as a first-line therapy in multiple tumor typesMerck’s $3 Billion Budget Shift: Preparing for Keytruda’s Post-Exclusivity Era and New Opportunities [https://medicinetomarket.com/mercks-3-billion-budget-shift-preparing-for-keytrudas-postexclusivity-era-and-new-opportunities/]^[1]. Meanwhile, AstraZeneca's Imfinzi has carved out a niche in limited-stage small cell lung cancer and muscle-invasive bladder cancer, but Keytruda's clinical data and earlier-stage indications provide a distinct advantageMarket Access and Reimbursement in Key European Markets and the US [https://petauri.com/insights/market-access-reimbursement-europe-us/]^[4].

Strategic Implications for Investors

The interplay of regulatory approvals, pricing dynamics, and competitive pressures defines Keytruda's trajectory in the EU. While Merck's budget reallocation toward R&D signals a proactive response to patent expiration, the drug's near-term success hinges on securing reimbursement for its SC formulation and head-and-neck cancer indication. Investors should monitor the European Commission's Q4 2025 decisions, as well as Merck's ability to maintain pricing stability in markets like Japan, where price erosion has impacted peersMerck Receives Two Positive EU CHMP Opinions for KEYTRUDA (pembrolizumab) for Subcutaneous (SC) Administration and for New Indication for Earlier-Stage Head and Neck Cancer [https://www.merck.com/news/merck-receives-two-positive-eu-chmp-opinions-for-keytruda-pembrolizumab-for-subcutaneous-sc-administration-and-for-new-indication-for-earlier-stage-head-and-neck-cancer/]^[3].

In the broader immuno-oncology landscape, Keytruda's leadership in NSCLC and bladder cancer—coupled with its subcutaneous convenience—positions it to outperform rivals in the short to medium term. However, the entry of biosimilars post-2028 and continued regulatory scrutiny of pricing will test Merck's long-term resilience. For now, the company's strategic agility and EMA's support for innovative pathways suggest Keytruda will remain a cornerstone of EU oncology care—and a key driver of Merck's financial performance.