Soaring off the Patent Cliff: Preparing for the Next Wave of Oncology Biosimilars

Biosimilars have already reshaped the oncology landscape, with products such as trastuzumab (Herceptin; Genentech), bevacizumab (Avastin; Genentech), and rituximab (Rituxan; Genentech) proving that, compared with high-cost biologics, biosimilars demonstrate no clinically meaningful differences in safety and efficacy while significantly reducing treatment expenditures.^1,2 These products validated the regulatory and clinical frameworks that underpin biosimilar development and adoption. The next generation of biosimilars promises to be even more transformative.

PD-1 inhibitors and other high-budget monoclonal antibodies are approaching the end of their market exclusivity in the US, which is expected to trigger a surge of new biosimilar entries and catalyze an era of competition in oncology therapeutics.^1,2 For pharmacists who guide formulary strategy, counsel patients, and manage infusion center operations, now is the critical time to understand what is coming, when these products may launch, and how to prepare for their impact on practice.

A Closer Look at the Near-Term Pipeline

Pembrolizumab (Keytruda; Merck) stands out as the most anticipated entry in this next wave and represents one of the most significant of these forthcoming opportunities.^1,2 The intravenous formulation of pembrolizumab is projected to lose US patent protection in 2028.^1-3 Multiple biosimilar development programs are underway, with public disclosures and analyst projections suggesting that regulatory submissions to the FDA could occur as early as 2026 or 2027.^1,2 These submissions could allow for FDA review and potential approval prior to the expiration of the primary patents, positioning biosimilars for potential market entry upon loss of exclusivity (LOE) in 2028, although this may depend on the outcomes of litigation, settlements, and the pace of the FDA's review.^1,2 The competitive impact is expected to be substantial, as pembrolizumab currently accounts for a significant share of oncology drug expenditures in the US.^1,2 The Table highlights several pembrolizumab biosimilars currently in clinical development.

Table. Pembrolizumab biosimilars active in the pipeline^a1,2

Pembrolizumab is not the only immune checkpoint inhibitor (ICI) approaching LOE. Nivolumab (Opdivo; Bristol Myers Squibb) is expected to lose US exclusivity in 2028, according to corporate disclosures.^1,2,4 Atezolizumab (Tecentriq; Genentech) is also expected to face biosimilar competition later in the decade.^1,2,5 Pertuzumab (Perjeta; Genentech), a HER2-directed monoclonal antibody, may see biosimilar competition between 2026 and 2027, while daratumumab/daratumumab-hyaluronidase (Darzalex/Darzalex Faspro; Janssen Biotech), a multiple myeloma backbone therapy, is being targeted by phase 3 biosimilar development programs that suggest US launches closer to the end of the decade.^1,2,6,7 Ipilimumab (Yervoy; Bristol Myers Squibb), a CTLA-4 inhibitor, also faces potential biosimilar competition in 2029 or later.^1,2

More Competition and Innovators’ Defense Mechanisms

Many innovative companies are pursuing strategies to defend their market position through product lifecycle management.^1,2 One such approach includes the development of a subcutaneous (SC) formulation of pembrolizumab designed to improve administration convenience and potentially differentiate the brand product even in the face of intravenous (IV) biosimilar competition.^1,2,8 This strategy is consistent with actions by several manufacturers of high-cost biologics, who have used SC formulations to retain market share and slow biosimilar uptake.

On September 19, 2025, the FDA approved pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex; Merck) SC injection for adult and pediatric patients 12 years and older for most of the solid tumor indications for which IV Keytruda is approved.^1,3,8,9 However, Keytruda Qlex is not FDA approved for hematologic malignancies, including classical Hodgkin lymphoma or primary mediastinal large B-cell lymphoma.^1,8 This product is the third SC ICI, following atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza; Genentech) and nivolumab and hyaluronidase-nvhy (Opdivo Qvantig; Bristol Myers Squibb), which were approved in 2024.^1,2 The emergence of both IV and SC formulations will require health systems and payers to develop policies that address interchangeability, site-of-care considerations, and reimbursement differentials.

Insights and Implications

The projected timing of biosimilar approvals and launches highlights the need for proactive planning. These dates remain subject to change due to litigation outcomes, patent settlements, and regulatory review timelines. Nevertheless, the broad outline is clear: The second half of this decade will be characterized by the steady introduction of biosimilars for some of the most expensive therapies in oncology.

The implications for pharmacy practice are significant. Pharmacists will need to ensure that formularies and contracting strategies are prepared to accommodate rapid product changes and payer preferences. Clinical governance structures must develop protocols to manage switching between originator products and biosimilars, while maintaining patient safety and therapeutic continuity. Electronic health record order sets will need to be updated to include biosimilar options, and revenue cycle operations must prepare for new national drug codes, reimbursement shifts, and potential product-specific prior authorizations. Patient communication will also be critical, as individuals undergoing cancer therapy must be reassured that biosimilars meet rigorous standards for safety, efficacy, and quality, supported by comprehensive comparative clinical data.

Looking forward, pharmacists must closely monitor FDA filings, approval decisions, and market launch announcements, as well as the introduction of originator defense strategies, such as SC formulations that may alter payer and provider decision-making. The anticipated LOE for pembrolizumab, nivolumab, atezolizumab, and other monoclonal antibodies will test the readiness of health systems to manage a complex therapeutic landscape while ensuring access and affordability.^1,10

Conclusion

If the past decade was about proving the biosimilar model in oncology, the next will be about executing at scale in the highest-spend categories. Pembrolizumab’s anticipated 2028 LOE sets the tone, with nivolumab and others close behind.¹ Pharmacies that standardize their playbooks—in contracting, clinical governance, inventory, and patient communication—will be best positioned to protect access, sustain quality, and capture the savings that make more innovation possible.

REFERENCES

1. Payer and provider insights: biosimilars. IPD Analytics. Accessed September 23, 2025. www.ipdanalytics.com

2. Biomedtracker Pharma Intelligence, Citeline Commercial, 2025. Accessed September 23, 2025. www.biomedtracker.com

3. Product patents. Merck. Updated September 2025. Accessed September 23, 2025. https://www.merck.com/products/patent/

4. Bristol Myers Squibb reports fourth quarter and full-year financial results for 2024. News release. Bristol Myers Squibb. February 6, 2025. Accessed September 23, 2025. https://www.bms.com/assets/bms/us/en-us/pdf/investor-info/doc_financials/quarterly_reports/2024/BMY-Q42024-Earnings-Press-Release.pdf

5. Atezolizumab - biologic drug details. Drug Patent Watch. Updated November 12, 2025. Accessed November 12, 2025. https://www.drugpatentwatch.com/p/biologics/ingredient/atezolizumab

6. Roche braces for late 2026 biosimilar wave. Citeline. July 31, 2025. Accessed September 23, 2025. https://insights.citeline.com/generics-bulletin/products/biosimilars/roche-braces-for-late-2026-biosimilar-wave-6VTOL2ZMGJEAPDBMSAFPEPP6M4/

7. Kansteiner F. J&J’s next-gen Darzalex sparks drug delivery royalties battle. Fierce Pharma. September 24, 2020. Accessed September 23, 2025. https://www.fiercepharma.com/pharma/genmab-takes-j-j-to-arbitration-court-over-subq-darzalex-royalties

8. 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). News release. Merck. September 23, 2025. Accessed September 23, 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/

9. Gardner J. Under-the-skin Keytruda comparable to infused version in Phase 3 study, Merck says. BioPharma Dive. November 19, 2024. Accessed September 23, 2025. https://www.biopharmadive.com/news/merck-subcutaneous-keytruda-phase-3-study-cancer/733341/

10. Yadav P, Corridon C, Mathuria M. The next frontier: oncology biosimilars in 2025 and beyond. AJMC. January 13, 2025. Accessed September 23, 2025. https://www.centerforbiosimilars.com/view/the-next-frontier-oncology-biosimilars-in-2025-and-beyond