Keytruda: Merck’s $31.7B Oncology Franchise, Patent Expiry and Competitive Strategy

KEYTRUDA (pembrolizumab) is a PD-1 inhibitor developed by Merck & Co. and is one of the company’s most important products.

Keytruda generated approximately $31.7 billion in worldwide sales in 2025, making it the central revenue driver of Merck’s pharmaceutical business.

Merck is continuing to expand Keytruda through additional indications, combinations and formulations. The company has also introduced KEYTRUDA QLEX, a subcutaneous formulation, giving Merck another way to extend the franchise and improve treatment convenience.

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Keytruda indicatorData
DrugPembrolizumab
BrandKEYTRUDA
Developer/commercial companyMerck & Co.
MechanismPD-1 inhibitor
2025 sales$31.7 billion
Key precision biomarkersPD-L1, MSI-H/dMMR, TMB-H
Major patent milestoneDecember 2028 compound patent expiry

Merck has stated that the Keytruda compound patent expires in December 2028. Merck’s financial materials also discuss revenue continuing beyond the patent-expiry period, with trough revenue expected around 2031.

This makes 2028–2031 a critical strategic period for Merck.

What Merck Is Doing to Protect Keytruda

Merck is not relying on one strategy to protect Keytruda revenue.

The company is focusing on:

  • Expanding Keytruda into additional cancer types
  • Moving treatment into earlier lines of therapy
  • Developing combination treatments
  • Expanding biomarker-defined indications
  • Developing Keytruda QLEX
  • Developing personalized cancer-treatment approaches
  • Building partnerships around next-generation oncology technologies

One of the most important moves is Merck’s collaboration with Moderna around an individualized mRNA cancer vaccine combined with Keytruda.

The Phase 3 study involved 1,137 patients with high-risk melanoma, testing the personalized vaccine plus Keytruda against Keytruda alone. This is particularly important because it connects Keytruda with patient-specific tumor mutation information rather than using immunotherapy as a broad treatment approach.

The strategic direction is therefore:

Keytruda → biomarkers → molecular testing → personalized combinations → longer-term franchise protection

Keytruda’s Patent Expiration Is the Major Strategic Issue

The December 2028 compound patent expiry is one of the most important issues for Merck.

The company has been preparing for this period by building additional growth drivers around Keytruda and its broader pipeline.

Merck’s own commentary indicates that the company expects Keytruda revenue to remain substantial after patent expiry, but the business will face increasing pressure from loss of exclusivity and potential competition.

Therefore, Merck needs to replace or protect billions of dollars of annual revenue before the patent cliff becomes commercially significant.

The Main Competitors and What They Are Doing

The most relevant competitors are other PD-1/PD-L1 oncology drugs, particularly:

  • Opdivo – Bristol Myers Squibb
  • Tecentriq – Roche
  • Libtayo – Regeneron/Sanofi
  • Jemperli – GSK

The important point is that these companies are not simply selling alternative checkpoint inhibitors.

They are trying to capture specific cancer types, biomarker-defined patients, treatment lines and combination opportunities.

Opdivo – Bristol Myers Squibb

OPDIVO (nivolumab) is Keytruda’s most important direct PD-1 competitor.

Bristol Myers Squibb reported approximately $10.05 billion in Opdivo sales in 2025, compared with approximately $9.30 billion in 2024.

BMS is differentiating Opdivo through:

  • Combination immunotherapy
  • Opdivo + Yervoy
  • Earlier-line treatment
  • Multiple tumor types
  • Subcutaneous delivery through Opdivo Qvantig
  • New biomarker-driven treatment opportunities

BMS estimates minimum U.S. market exclusivity for Opdivo Qvantig into 2028, while certain underlying patents extend beyond that depending on jurisdiction and patent.

What this means for Merck:
BMS is attacking Keytruda through combination treatment, treatment convenience and lifecycle management, rather than trying to copy Keytruda’s entire indication base.

Tecentriq – Roche

TECENTRIQ (atezolizumab) is Roche’s PD-L1 inhibitor.

Roche reported CHF 3.566 billion in Tecentriq sales in 2025. Roche has also indicated that Tecentriq sales are under pressure in some settings, making lifecycle management and new applications increasingly important.

Roche’s strategy is particularly interesting because the company has strong capabilities in:

  • Companion diagnostics
  • Genomic testing
  • Biomarker identification
  • ctDNA
  • Minimal residual disease
  • Personalized treatment selection

This creates an integrated model:

Drug + diagnostic + patient identification + molecular monitoring

That is a significant competitive advantage in precision oncology.

Libtayo – Regeneron and Sanofi

LIBTAYO (cemiplimab) is another PD-1 inhibitor.

Regeneron records global Libtayo sales and pays Sanofi a royalty on those sales.

Rather than trying to replicate Keytruda’s enormous indication breadth, Libtayo has built a strong position around selected cancers and treatment settings.

Its strategy demonstrates how a smaller oncology franchise can compete through high-value patient segments and differentiated clinical evidence.

Jemperli – GSK

JEMPERLI (dostarlimab) is particularly important in biomarker-defined oncology.

GSK reported £861 million in Jemperli sales in 2025, up 84%.

GSK’s 2025 annual report states that Jemperli has patent protection extending to at least 2040, giving the company a considerably longer potential protection period than Keytruda’s core compound patent.

This is strategically important.

GSK can build around dMMR/MSI-H patient populations while having a long runway for commercialization.

Patent and Sales Comparison

DrugCompany2025 salesKey patent/exclusivity consideration
KeytrudaMerck$31.7BCore compound patent expires Dec. 2028
OpdivoBristol Myers Squibb$10.05BKey exclusivity/patent positions extend into late 2020s/2030s depending on product
TecentriqRocheCHF 3.566BPatent/exclusivity varies by jurisdiction and formulation
JemperliGSK£861MProtection reported through at least 2040
LibtayoRegeneron/SanofiLower than Keytruda/OpdivoMultiple patent considerations; jurisdiction-specific

Patent dates should not be treated as a single global “drug expiry” date. Composition-of-matter patents, formulation patents, method-of-use patents, pediatric exclusivity and jurisdiction-specific protections can produce different loss-of-exclusivity dates.

What Companies Should Do Next

For Merck, the priority should be reducing dependence on the 2028 Keytruda patent milestone.

Build the next Keytruda revenue engines

Merck should continue investing in:

  • Personalized cancer vaccines
  • ADC combinations
  • Targeted therapies
  • New immunotherapy combinations
  • Earlier-stage disease
  • Biomarker-defined indications

Protect the franchise through formulation

Keytruda QLEX provides another lifecycle-management opportunity.

Merck should use convenience, administration time and patient experience to differentiate the product as competition develops.

Invest heavily in diagnostics

The future competitive advantage is not just the drug.

It is:

Who gets tested → what biomarker is found → which treatment is selected → how response is monitored.

Merck therefore needs stronger integration with genomic-testing, companion-diagnostic and molecular-monitoring companies.

Prepare for the 2028 patent cliff now

Merck needs to identify exactly which products and pipeline assets will replace Keytruda revenue after loss of exclusivity.

The relevant question is not simply:

“What will replace Keytruda?”

It is:

“Which combination of products, indications, formulations and personalized therapies will replace the revenue?”

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Who Are the Actual Buyers?

For Keytruda and competing immunotherapies, the “buyer” is not simply the patient.

The purchasing and decision-making ecosystem includes:

Hospitals and cancer centers

Large oncology hospitals and academic cancer centers are major treatment decision points.

They evaluate:

  • Clinical evidence
  • Guidelines
  • Biomarker requirements
  • Treatment outcomes
  • Administration requirements
  • Cost
  • Patient population

Oncologists

Oncologists are the critical clinical decision-makers.

They need information about:

  • Patient eligibility
  • Biomarker status
  • Treatment line
  • Combination options
  • Safety
  • Response rates
  • Resistance
  • Duration of treatment

Diagnostic companies and laboratories

These are increasingly important because precision oncology depends on identifying the correct patient.

Relevant technologies include:

  • PD-L1 testing
  • MSI/MMR testing
  • Tumor sequencing
  • TMB testing
  • Liquid biopsy
  • ctDNA
  • MRD testing

Pharmaceutical and biotech companies

These companies are potential partners, licensors and technology providers.

They are looking for opportunities around:

  • Combination therapies
  • Biomarkers
  • Companion diagnostics
  • Cancer vaccines
  • ADCs
  • Targeted therapies
  • Molecular monitoring

Patients

Patients increasingly influence treatment decisions through demand for:

  • Personalized treatment
  • Better outcomes
  • Fewer unnecessary therapies
  • Faster testing
  • Convenient administration
  • Treatment options based on their individual tumor biology

Where Are the Buyers?

The highest-value buyer ecosystems are concentrated around major oncology and biotechnology hubs.

United States

The U.S. is the most important commercial and clinical ecosystem because of its large oncology-treatment infrastructure, academic cancer centers, pharmaceutical companies, diagnostic companies and clinical-trial activity.

Key hubs include:

Boston/Cambridge, Massachusetts
Biotech, oncology R&D and precision-medicine companies.

New York/New Jersey
Major pharmaceutical companies, hospitals and oncology networks.

California
Biotech, diagnostics, cancer centers and venture-backed oncology companies.

Pennsylvania
Major oncology research and pharmaceutical infrastructure.

Europe

Important buyer and research ecosystems include:

  • Germany
  • United Kingdom
  • France
  • Switzerland
  • Netherlands

These markets are particularly relevant for pharmaceutical companies developing biomarker-driven oncology products and companion diagnostics.

Asia-Pacific

Important oncology and precision-medicine ecosystems include:

  • Japan
  • China
  • South Korea
  • Singapore
  • Australia

These regions provide opportunities around clinical development, diagnostics, oncology treatment and pharmaceutical partnerships.

What Towards Healthcare Research & Consulting Provides

For oncology pharmaceutical and biotech leaders, the useful intelligence is not simply a list of Keytruda competitors.

Towards Healthcare Research & Consulting can connect the commercial, clinical and strategic information required for decision-making:

Drug intelligence – Sales, revenue contribution, indications, approvals, formulations, clinical development and lifecycle strategy.

Company intelligence – Where Merck and competitors are investing, which partnerships they are forming and where they are allocating R&D resources.

Competitor intelligence – Opdivo, Tecentriq, Jemperli, Libtayo and emerging oncology therapies, including their clinical programs, investments and strategic positioning.

Patent intelligence – Key patent families, expected loss-of-exclusivity timelines, formulation protection and competitor patent positions.

Buyer identification – Hospitals, cancer centers, oncologists, diagnostic laboratories, pharmaceutical companies and biotech companies that influence purchasing and treatment decisions.

Geographic intelligence – Where the highest-value oncology buyers, clinical programs, diagnostic capabilities and investment opportunities are located.

Strategic recommendations – What companies should invest in, which competitors they need to monitor, which patient segments they should target and where opportunities exist before major patent-expiry events.

The strategic picture around Keytruda is therefore:

$31.7B drug → December 2028 core patent milestone → Merck’s lifecycle investments → Opdivo/Tecentriq/Jemperli/Libtayo competition → biomarker and diagnostic integration → personalized oncology → next-generation revenue opportunities.

That is the level of company, drug, competitor, patent, buyer and investment intelligence pharma and biotech leaders need to make their next strategic decision.

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