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When Delivery Becomes Strategy: Merck’s Subcutaneous Keytruda

  • Fraol Galan
  • 1 day ago
  • 7 min read

Updated: 7 hours ago

In oncology, innovation usually means new mechanisms, biomarkers, or combinations. But on September 19, 2025, Merck shifted that narrative (1). The FDA approved a subcutaneous (SC) version of Keytruda—co-formulated with berahyaluronidase alfa for rapid under-the-skin absorption—across all existing intravenous (IV) Keytruda indications for patients twelve and older.


The approval may seem technical, but its impact is structural: it compresses a 30-minute infusion into a 1-2 minute injection, freeing scarce capacity in oncology clinics and reshaping how value is created in cancer care. In short, Merck elevated delivery from an operational consideration to a core element of its oncology strategy. This milestone doesn’t change the science of immuno-oncology—it changes the economics of how cancer care is delivered.


The approval may seem technical, but its impact is structural: it compresses a 30-minute infusion into a 1-2 minute injection, freeing scarce capacity in oncology clinics and reshaping how value is created in cancer care.

From Thirty Minutes to One—or Two (By Regimen) 


For nearly a decade, every Keytruda dose required a 30-minute IV infusion, occupying infusion chairs, pharmacy prep, and nursing time (2). Now, the same therapy can be delivered subcutaneously—about one minute for the 395 mg Q3W regimen or two minutes for the 790 mg Q6W regimen (1,3,4). The pivotal study evaluated only the Q6W regimen, with a median injection time of 2 minutes.


In MK-3475A-D77, Merck demonstrated non-inferior pharmacokinetics and comparable efficacy and safety versus IV pembrolizumab. Time-and-motion analysis showed roughly 50% reductions across patient chair, room, and staff time, highlighting the operational efficiency of the SC format (5). While SC delivery isn’t new to oncology, Keytruda’s rollout brings this efficiency dynamic to the core of mainstream immunotherapy—showing how delivery can reinforce competitive position in a scale-defining franchise.


The result highlights a shift in how oncology value is delivered—no longer defined by efficacy and safety alone, but by how franchises innovate through delivery and access to reach more patients per hour.


The result highlights a shift in how oncology value is delivered—no longer defined by efficacy and safety alone, but by how franchises innovate through delivery and access to reach more patients per hour.

Route of Administration as a Strategic Lever 


For years, route of administration has long been part of pharma’s competitive toolkit—from self-injectors in immunology to oral switches in oncology—but its relevance rises and falls with clinical and operational context. Even when subcutaneous biologics entered oncology, uptake was uneven—that dynamic is shifting (6,7,8). 


Today, that relevance is being renewed by mounting operational constraints across oncology practices. Capacity and staffing pressure are real but distinct issues. In 2022 ACCC/LeanTaaS survey data, about 40% of infusion leaders said they had run out of space and would require physical expansion; in 2023 follow-up data, 64% of centers reported staffing shortages were causing challenges (9,10). 


Today, that relevance is being renewed by mounting operational constraints across oncology practices.

In that context, SC Keytruda is more than a convenience—it’s capacity creation (11). Compressing administration from 30 minutes to 1–2 minutes lets practices boost throughput without new staff or space. As PD-1 efficacy converges, workflow efficiency emerges as a critical differentiator—shaping how prescribers, payers, and patients experience value. 


Competitive and Economic Context 


Keytruda isn’t the first oncology biologic to go SC. Rituxan Hycela (rituximab SC) won FDA approval June 22, 2017 (12); Herceptin Hylecta (trastuzum ab SC) followed on February 28, 2019 (13); and Tecentriq Hybreza (atezolizumab SC) arrived September 12, 2024 (14). These precedents—particularly trastuzumab—provide years of real-world data on how SC oncology biologics can impact practice (15). 


By extending the franchise through delivery innovation, Merck is leveraging route of administration as a lifecycle lever—a timely, scalable differentiator ahead of loss of exclusivity. In the U.S., IRA-negotiated prices are expected to take effect January 2028, coinciding with a key patent expiring at the end of 2028; the EU patent tail extends later, shaping geography-specific strategies (16)

. 

But reimbursement is a headwind. In 2024, SC administration reimbursement was reported to be ~45% lower than IV—creating a substantial financial disincentive for buy-and-bill practices (17,18). Throughput gains may not fully offset revenue deltas unless payer models evolve to reward efficiency. 


By extending the franchise through delivery innovation, Merck is leveraging route of administration as a lifecycle lever—a timely, scalable differentiator ahead of loss of exclusivity.

The Emerging Site-of-Care Shift 


The implications extend beyond infusion bays. As U.S. oncology care migrates from hospitals to outpatient settings, injections revive possibilities once remote – retail or even home-based administration. Current FDA labeling requires administration by a healthcare professional, and patient-facing and promotional materials are consistent with that requirement. Hope for home administration requires measured optimism. Trials are exploring home administration models for subcutaneous cancer therapies (19,20), but regulatory and reimbursement barriers remain material, and oncology lags other therapeutic areas (e.g., diabetes, rheumatology) in this transition (17, 21,22). 


Trials are exploring home administration models for subcutaneous cancer therapies (19,20), but regulatory and reimbursement barriers remain material, and oncology lags other therapeutic areas...

Subcutaneous biologics could accelerate the decentralization of cancer care—provided the economics and guardrails line up. 


Challenges and Caveats 


Change will not be uniform. Each barrier—economic, operational, and communicative—will determine how quickly subcutaneous oncology delivery translates from efficiency promise to clinical reality. Lower SC administration payments versus IV create drag in buy-and-bill settings; some clinics may still prefer IV revenue even if SC frees capacity (18). 


Operationally, injection-volume limits and cold-chain logistics restrict which antibodies can transition. Reported time savings are compelling, but real-world gains depend on staffing patterns, room turnover, and billing codes (5). Messaging discipline also matters: “two minutes” reflects the Q6W regimen tested in the pivotal trial, while “one minute” represents the labeled Q3W regimen based on flow-rate extrapolation (23).  

Still, the direction of travel is clear—once patients and providers experience speedy injections, expectations may reset.  


The View from the Crow’s Nest


Merck’s subcutaneous Keytruda isn’t merely a formulation milestone—it’s the latest signal of how delivery innovation continues to shape oncology value. As efficacy and safety gaps narrow, delivery efficiency is becoming an increasingly relevant dimension of competition. 


For biopharma leaders in oncology, three imperatives stand out: 


  1. Integrate delivery efficiency into pipeline and lifecycle evaluation. Quantify administration time, staffing needs, and throughput economics as formal inputs to development and commercialization planning, using study-grade time-and-motion data rather than assumptions.

  2. Invest early in formulation and device capabilities. Partnerships and platforms that de-risk SC development can unlock margin protection while earning payer and provider preference in capacity-constrained system.

  3. Enable site-of-care diversification through design and partnerships. Develop subcutaneous formulations, delivery devices, and supply-chain collaborations that improve visibility and readiness for non-hospital administration once regulations permit. 


Subcutaneous Keytruda doesn’t end the infusion era—it marks its inflection point. It shows that innovation in how an oncology drug is delivered can reshape markets as profoundly as innovation in what it targets. 

 

If you are interested in learning more, get in touch at strategy@spinnakerLS.com. 

Spinnaker offers true partnership and comprehensive guidance to help leaders navigate the complexities of the Life Sciences industry and chart a path to success. From early-stage market assessment through commercial execution and ongoing lifecycle management, we deliver tailored solutions to ensure optimized practicable results.

Sources:

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  2. Merck & Co., Inc. How KEYTRUDA is given. Keytruda.com; Accessed October 21, 2025. https://www.keytruda.com/taking-keytruda/ 

  3. Merck & Co., Inc. FDA Approves Merck's KEYTRUDA QLEX™ (pembrolizumab and berahyaluronidase alfa-pmph) Injection for Subcutaneous Use in Adults Across Most Solid Tumor Indications for KEYTRUDA® (pembrolizumab). Merck News Center; September 19, 2025. https://www.merck.com/news/fda-approves-mercks-keytruda-qlex-pembrolizumab-and-berahyaluronidase-alfa-pmph-injection-for-subcutaneous-use-in-adults-across-most-solid-tumor-indications-for-keytruda-pem/ 

  4. Clarke H, Saylor BP. FDA approves pembrolizumab for subcutaneous injection for solid tumors. Urology Times; September 19, 2025. https://www.urologytimes.com/view/fda-approves-pembrolizumab-for-subcutaneous-injection-for-solid-tumors 

  5. Merck & Co., Inc. Merck’s Investigational Subcutaneous Pembrolizumab With Berahyaluronidase Alfa Demonstrates Noninferior Pharmacokinetics Compared to Intravenous (IV) KEYTRUDA® (pembrolizumab) in Pivotal 3475A-D77 Trial. Merck News Center; March 27, 2025. https://www.merck.com/news/mercks-investigational-subcutaneous-pembrolizumab-with-berahyaluronidase-alfa-demonstrates-noninferior-pharmacokinetics-compared-to-intravenous-iv-keytruda-pembrolizumab-in-pivotal/ 

  6. 6 Bittner B, Richter W, Schmidt J. Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities. BioDrugs. 2018;32(5):425–440. doi:10.1007/s40259-018-0295-0. https://pmc.ncbi.nlm.nih.gov/articles/PMC6182494/ 

  7. 7 Abad-Sazatornil MR, Arenaza A, Bayo J, et al. Impact of the subcutaneous formulations of trastuzumab and rituximab on efficiency and resource optimization in Spanish hospitals: H-Excelencia study. BMC Health Serv Res. 2021;21:320. doi:10.1186/s12913-021-06277-8. https://pmc.ncbi.nlm.nih.gov/articles/PMC8034176/ 

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  12. 12 U.S. Food and Drug Administration. FDA approves rituximab plus hyaluronidase combination treatment for FL, DLBCL, and CLL. FDA; June 22, 2017. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-rituximab-plus-hyaluronidase-combination-treatment-fl-dlbcl-and-cll 

  13. 13 U.S. Food and Drug Administration. FDA approves new formulation of Herceptin for subcutaneous use. FDA; February 28, 2019. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-new-formulation-herceptin-subcutaneous-use 

  14. 14 U.S. Food and Drug Administration. FDA approves atezolizumab and hyaluronidase-tqjs for subcutaneous injection. FDA; December 21, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-and-hyaluronidase-tqjs-subcutaneous-injection 

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  16. 16 FiercePharma. Merck expects Keytruda to fall to IRA price cuts in 2028. FiercePharma; October 18, 2023. https://www.fiercepharma.com/pharma/merck-expects-keytruda-fall-ira-price-cuts-2028 

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  19. 19 A Study to Evaluate Patient Preference for Home Administration of Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Administration in Participants With Early or Locally Advanced/Inflammatory HER2-Positive Breast Cancer (ProHer). ClinicalTrials.gov Identifier: NCT05415215. Hoffmann-La Roche; Accessed October 21, 2025. https://clinicaltrials.gov/study/NCT05415215 

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