How MFN Pricing Is Reshaping Pharmaceutical Strategy: From M&A Deal Structures to Global Launch Decisions

https://www.pharmexec.com/view/most-favored-nation-policy-outlook-implications-beyond

The pharmaceutical industry stands at an inflection point. Most Favored Nation (MFN) pricing mechanisms introduced through the Trump administration’s 2025 executive actions aren’t just regulatory compliance issues, they’re fundamentally altering how we think about asset valuation, deal economics, and global commercialization strategy. At Alira Health, our work with clients navigating these shifts reveals a landscape where traditional playbooks no longer apply.

The MFN Reality: Not Just Policy, But a Business Transformation

The implementation of GLOBE (Medicare Part B), GUARD (Medicare Part D), and GENEROUS (Medicaid) represents the first meaningful introduction of international price benchmarks into U.S. pharmaceutical pricing. While the U.S. will remain the highest-priced market, these mechanisms are designed to narrow the most extreme pricing differentials, particularly in therapeutic areas where U.S. prices have historically been 4–5x higher than comparable developed markets.

Internal Analysis on Public Sources

What’s often missed in policy discussions is how profoundly this affects strategic decision-making. In oncology and rare diseases, areas where I focus much of my work, the implications vary dramatically based on patient population, therapeutic differentiation, and the specific modality involved.

M&A in the MFN Era: A New Deal Calculus

The pharmaceutical M&A landscape in 2025 tells an interesting story. After a cautious first half marked by uncertainty around Trump administration policies, we’ve seen deal activity surge to approximately $179 billion year-to-date, up 31% from 2024. Notably, mega-deals are back: Novartis acquiring Avidity Biosciences for $12 billion, Merck’s purchases of Verona Pharma and Cidara Therapeutics for $10 billion and $9.2 billion respectively.

Yet these headline numbers mask a more nuanced reality. We’re increasingly brought in to assess MFN-specific risks during due diligence, analysis that simply didn’t exist two years ago. The questions we help clients answer include:

Asset-Level MFN Exposure Analysis: Pediatric rare diseases with negligible Medicare exposure present fundamentally different risk profiles than chronic conditions in elderly populations. A hemophilia therapy targeting pediatric patients faces minimal direct MFN impact compared to a cardiovascular drug prescribed primarily to Medicare beneficiaries.

Therapeutic Area Pricing Dynamics: Oncology and Rare Disease assets often demonstrate compressed U.S.-to-ex-U.S. price ratios (frequently under 2x), making them structurally more resilient to MFN-driven pricing pressure than, say, diabetes or cardiovascular therapeutics where ratios commonly exceed 4x. This isn’t merely academic, it directly impacts how we model sustainable global pricing assumptions in transaction valuations.

Company-Specific MFN Commitments: Among the 16 manufacturers with dedicated MFN pricing agreements as of January 2026, implementation varies significantly. Some have negotiated modified versions of GENEROUS, GLOBE, and GUARD. This introduces company-level risk layered atop asset-specific exposure, a complexity that demands granular assessment rather than portfolio-level approximations.

Shifting Deal Structures: Risk Distribution in an Uncertain Environment

Traditional pharma M&A relied on relatively predictable revenue forecasts to justify upfront payments. MFN introduces greater pricing uncertainty, fundamentally challenging these underwriting assumptions. We’re seeing several structural responses:

1. Contingent Payments Over Upfront Cash: Deal economics are increasingly weighted toward post-launch, revenue-based milestones rather than large upfront payments. This distributes MFN-related pricing risk between buyer and seller, acknowledging that sustainable global pricing won’t be fully clear until products navigate both U.S. payer negotiations and international HTA processes.

2. Scenario-Based Valuation Frameworks: Rather than single-point revenue projections, sophisticated buyers now model multiple pricing scenarios reflecting different MFN impacts. The gap between optimistic and pessimistic cases can be substantial, particularly for assets where ex-U.S. markets represent 30–40% of projected long-term value.

3. Downside Protection Mechanisms: We’re advising clients to build in contractual protections tied to MFN-related pricing outcomes, including ratchet provisions that adjust payment obligations if certain price benchmarks aren’t achieved.

The Ex-U.S. Strategy Question: Is European Launch Worth It?

Here’s where MFN creates genuinely difficult strategic choices, particularly for U.S.-based biotechs. If achieving attractive ex-U.S. pricing becomes structurally harder under MFN reference dynamics, does European commercialization still make economic sense?

The data on European launches by U.S. first-time launchers is sobering: of 141 novel drugs launched in the U.S. between 2011–2024, fewer than half (66) subsequently launched in Europe. Another 33 remain in active EU development, while 13 were explicitly withdrawn from European pathways. We’re talking about high-value, innovative therapies that simply aren’t available to European patients, a trend that MFN may accelerate.

For smaller biotechs, the calculus is stark. European market access requires significant investment in HTA submissions, pricing negotiations across fragmented national systems, and commercial infrastructure, all for markets that may only accept pricing at 40–60% of U.S. levels. If those lower European prices then become reference points that pressure U.S. Medicare pricing downward through MFN mechanisms, the entire global value proposition deteriorates.

In my work with oncology and rare disease companies, I’m seeing three emerging approaches:

• Selective European Penetration: Rather than pan-European strategies, companies are prioritizing 3–5 key markets (Germany, UK, France) where pricing potential justifies the investment, while de-prioritizing or avoiding markets with more restrictive pricing.
• Narrow Label Strategies: Some are pursuing deliberately restricted European regulatory labels focused on highest-unmet-need patient subpopulations, enabling higher per-patient pricing in exchange for smaller volumes. This works best for truly differentiated assets with strong clinical evidence in well-defined patient segments.
• Delayed European Entry: Others are launching in the U.S. first, establishing commercial traction and clinical evidence, then approaching European markets from a position of strength 12–18 months later. This allows time to build real-world evidence and potentially negotiate from demonstrated value rather than theoretical projections.

Critically, only assets offering substantial therapeutic improvement in high-unmet-need areas can realistically secure both broad European access and pricing approaching U.S. levels. For everything else, trade-offs are unavoidable.

The China Variable: Innovation Economics That Complicate MFN Dynamics

Any discussion of global pharmaceutical strategy in 2025 must grapple with China’s emergence as an innovation exporter. The numbers are striking: Chinese companies signed 157 out-licensing deals worth $136 billion in 2025, up from 94 deals worth $52 billion in 2024. In the first half of 2025, 32% of global pharmaceutical out-licensing value involved China-origin assets.

This isn’t about me-too drugs anymore. We’re talking about first-in-class and best-in-class candidates, particularly in oncology biologics, antibody-drug conjugates, bispecifics, and next-generation cell therapies. Major deals include AstraZeneca’s $5+ billion collaboration with CSPC Pharmaceutical for AI-driven cancer drug discovery, and GSK’s $12 billion alliance with Jiangsu Hengrui covering a dozen oncology programs.

From an MFN perspective, China introduces a fascinating dynamic. Chinese assets typically command 60–70% lower upfront payments than Western comparables, with total deal values 40–50% smaller. This cost advantage is attracting Western pharma facing patent cliffs and pricing pressure. But here’s the strategic question: if U.S. companies increasingly in-license innovation from China at lower costs, while MFN simultaneously pressures U.S. pricing toward international levels, what happens to the economic incentive for domestic innovation?

For European biotechs, China presents both opportunity and threat. The opportunity: partnering with or licensing from Chinese innovators to access cutting-edge science at attractive economics. The threat: competing for Western pharma partnerships against Chinese firms that can offer similar or better science at lower cost and faster development timelines.

Rare Diseases and Oncology: Where MFN Impact Diverges

In rare diseases, particularly orphan indications with small patient populations, MFN exposure can be quite limited. Pediatric rare disease patients rarely access Medicare, and participation in voluntary GENEROUS programs remains low for many orphan drugs. This has implications:

• Rare disease M&A remains structurally attractive under MFN, particularly for pediatric indications where Medicare exposure is minimal
• Cell and gene therapies often show compressed U.S.-ex-U.S. price ratios due to value-based pricing frameworks, making them less vulnerable to MFN reference-based pressure
• European rare disease markets may remain viable commercial targets, as pricing in these therapeutic areas has historically been more globally aligned

Oncology presents a more complex picture. Adult oncology clearly has Medicare exposure, but pricing dynamics vary by modality:

• Specialty oncology drugs (particularly for Part B administration) face meaningful GLOBE exposure
• Oral oncology therapeutics under Part D face GUARD implications
• Novel modalities (ADCs, bispecifics, radioligand therapies) often demonstrate better relative global pricing, as clinical differentiation can support value-based arguments in both U.S. and ex-U.S. markets

Practical Implications: What Should Companies Do Now?

Based on my work helping clients navigate this landscape, several actions are critical:

1. Conduct Asset-Specific MFN Risk Assessment Early: Don’t wait until you’re in active deal discussions or launching. Model payer mix, therapeutic area pricing dynamics, and potential MFN exposure as part of core portfolio strategy.

2. Build Robust Ex-U.S. Pricing Strategy Alongside Clinical Development: For assets with meaningful ex-U.S. commercial potential, develop strong value dossiers, engage payers early, and create evidence packages that support pricing closer to U.S. levels. This is particularly important for compounds addressing high unmet need with clear clinical differentiation.

3. Consider Launch Sequencing Strategically: The traditional “launch everywhere fast” approach may not optimize long-term value under MFN. Thoughtful sequencing-starting in markets where you can secure favorable pricing that won’t undermine future negotiations elsewhere-becomes increasingly important.

4. Reassess European Commercialization Plans: Be honest about whether European launch economics still work. For many biotechs, selective European entry or strategic partnerships may deliver better risk-adjusted returns than full go-alone strategies.

5. Stay Informed on China Innovation: Whether you view Chinese biotech as partner, competitor, or acquisition target, ignoring this innovation source is increasingly untenable. Understanding Chinese development capabilities and deal economics is now table stakes for strategic planning.

6. Evolve Transaction Due Diligence: If you’re buying or selling assets, ensure your diligence covers MFN implications comprehensively. This means moving beyond simple “rest-of-world revenue” multipliers to genuine understanding of sustainable global pricing under various regulatory scenarios.

Internal Analysis

Looking Ahead: A More Complex, But Navigable Future

MFN doesn’t make pharmaceutical innovation impossible, it makes it more complex. Companies that approach this complexity strategically, with sophisticated understanding of payer dynamics, global pricing interdependencies, and evolving innovation sources, will continue to create substantial value.

What’s clear is that the old playbook, launch in the U.S. at premium pricing, extrapolate internationally with modest adjustments, execute M&A based on relatively predictable revenue curves, no longer applies. The new playbook requires:

• Deeper integration of commercial, market access, and corporate development strategy
• Earlier engagement with ex-U.S. pricing and access considerations during R&D
• More sophisticated modeling of global pricing interdependencies
• Greater willingness to make difficult strategic choices about geographic prioritization

For those willing to adapt, the opportunities remain substantial. Therapeutic innovation still commands value when it addresses genuine unmet medical need with meaningful clinical differentiation. But capturing that value requires navigating a more intricate global landscape where pricing, regulatory, and competitive dynamics are increasingly interconnected.

We’re working daily with clients thinking through these strategic challenges. The companies that will thrive in this environment are those that recognize MFN not as an isolated regulatory hurdle, but as one element of a fundamentally reshaped strategic landscape requiring new approaches to innovation, commercialization, and growth.

What challenges are you seeing as your organization navigates MFN and evolving global pricing dynamics? I’d welcome your perspectives in the comments.

About the Author: Andrea Mantovani is a Senior Partner at Alira Health, specializing in commercial strategy, market access, and transaction support for pharmaceutical and biotechnology companies, with particular focus on oncology and rare diseases.

1. GlobalData Pharma Intelligence Center. “Pharma M&A deal value up 31% YoY in 2025YTD amid return of mega-deals.” Pharmaceutical Technology, December 2025. https://www.pharmaceutical-technology.com/analyst-comment/pharma-ma-deal-value-2025-ytd-mega-deals/
2. Alvarez & Marsal. “2024 Global Biopharmaceutical M&A and VC Insights.” December 2024. https://www.alvarezandmarsal.com/insights/2024-biopharmaceutical-ma-venture-capital-insights
3. McKinsey & Company. “Pulse check: Key trends shaping biopharma dealmaking in 2025.” June 2025. https://www.mckinsey.com/industries/life-sciences/our-insights/the-synthesis/pulse-check-key-trends-shaping-biopharma-dealmaking-in-2025
4. Drug Discovery Trends. “2025 pharma M&A surges to $70 billion in major deals.” October 2025. https://www.drugdiscoverytrends.com/2025-pharma-ma-surges-to-70-billion/
5. Fierce Pharma. “After a ‘reset’ year for M&A, expect bigger deals in 2025: reports.” January 2025. https://www.fiercepharma.com/pharma/after-reset-year-ma-expect-bigger-deals-2025-ey-report
6. PharmaVoice. “Will 2025 mark pharma’s pivot to bigger deals after years of lackluster M&A?” January 2025. https://www.pharmavoice.com/news/pharma-dealmaking-2025-outlook/737225/
7. BioPharma Dive. “M&A recap: Big pharma starts the year mostly avoiding billion-dollar deals.” Updated December 2025. https://www.biopharmadive.com/news/pharma-biotech-dealmaking-first-quarter-2025-size/744410/
8. BioSpace. “The 7 Most Impactful M&A Deals of 2025.” December 2025. https://www.biospace.com/business/the-7-most-impactful-m-a-deals-of-2025
9. BioPharma APAC. “China’s Biopharma Dealmaking Surges in H1 2025, Driven by Record Licensing and Oncology Focus.” 2025. https://biopharmaapac.com/report/60/6738/chinas-biopharma-dealmaking-surges-in-h1-2025-driven-by-record-licensing-and-oncology-focus.html
10. EC Innovations. “China’s Biopharma Boom in Global Drug Licensing Deals.” November 2025. https://www.ecinnovations.com/blog/chinas-biopharma-boom-in-global-drug-licensing-deals/
11. Pharmaceutical Technology. “High-value oncology deals drive China’s drug licensing boom.” December 2025. https://www.pharmaceutical-technology.com/features/china-pharma-licensing-deals-oncology-innovative-drugs/
12. ARC Group. “China Innovative Pharma Going Global.” July 2025. https://arc-group.com/china-innovative-pharma/
13. GaBI Online. “More China licence deals for US drug companies.” 2025. https://gabionline.net/reports/more-china-licence-deals-for-us-drug-companies
14. BioPharma Dive. “Drugs from China are reshaping biotech. Track the licensing deals here.” Updated January 2026. https://www.biopharmadive.com/news/china-biotech-drug-licensing-deals-pipeline/758283/
15. Nature Reviews Drug Discovery. “Analysis of China-to-West pharmaceutical licensing deals in 2024.” April 2025. https://www.nature.com/articles/d41573-025-00068-0
16. Fierce Biotech. “China biotechs ‘reshaping’ US biopharma as outlicensing deals rise 11%: Jefferies report.” July 2025. https://www.fiercebiotech.com/biotech/china-biotechs-reshaping-us-biopharma-outlicensing-deals-rise-11-jefferies-report
17. Chemical & Engineering News. “China’s biotech industry is on the rise. Will it reshape global pharma?” September 2025. https://cen.acs.org/pharmaceuticals/drug-development/Chinas-biotech-industry-rise-reshape/103/web/2025/09
18. South China Morning Post. “Chinese drug makers strike a record US$136 billion in out-licensing deals in 2025.” January 2026. https://www.scmp.com/business/china-business/article/3339011/chinese-drug-makers-strike-record-us136-billion-out-licensing-deals-2025
19. ZS Associates. “US and European first launch trends and implications for emerging biopharma.” September 2025. https://www.zs.com/insights/us-novel-first-launches-implications-emerging-biopharma
20. Deloitte. “Expanding into European Biotech.” January 2022. https://www.deloitte.com/us/en/insights/industry/life-sciences/expanding-into-european-biotech-industry.html
21. Deloitte UK. “Biotech European expansion: Unlocking success through a go-alone strategy.” January 2025. https://www.deloitte.com/uk/en/services/consulting/research/biotech-european-expansion.html
22. Foothold America. “How UK & European Biotech Founders Commercialize Without Giving it All Away.” 2025. https://www.footholdamerica.com/blog/make-it-big-in-america-how-uk-european-biotech-founders-commercialize-without-giving-it-all-away/
23. DCAT Value Chain Insights. “The Biotech Landscape in 2025 and Beyond: Is a Rebound in the Making or Not?” October 2025. https://www.dcatvci.org/features/the-biotech-landscape-in-2025-and-beyond-is-a-rebound-in-the-making-or-not/
24. Pharmaceutical Executive. “Emerging Biopharma Launches: Strategizing in Today’s Global Market.” March 2025. https://www.pharmexec.com/view/emerging-biopharma-launches-strategizing-in-today-s-global-market
25. pharmaphorum. “Cracking the code: How European biotechs can win in the US market.” 2025. https://pharmaphorum.com/digital/cracking-code-how-european-biotechs-can-win-us-market
26. Ernst & Young. “EY Biotech Beyond Borders Report 2025.” June 2025. https://www.ey.com/en_us/life-sciences/biotech-outlook
27. Qubit Capital. “Biotech Startup Funding 2026: Strategies to Attract Angel Investors.” January 2026. https://qubit.capital/blog/mastering-biotech-startup-funding-strategies
28. U.S. Department of Health and Human Services. “Executive Orders and Policy Documents on Most Favored Nation Pricing.” 2025.
29. Stifel. “Biopharmaceutical Outlook for 2025.” 2025.
30. Jefferies Equity Research. “China Biotech Business Development Report.” July 2025.

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