A year ago, the debate surrounding the Most-Favored-Nation (MFN) model centered on a fundamental question: would international reference pricing create a more sustainable global benchmark, or introduce new risks across pharmaceutical markets? At the time, concerns focused on market disruption, access inequities, and the challenge of comparing fundamentally different healthcare systems.
Today, those concerns remain relevant, but the discussion has evolved. Initially, there were three strategic approaches to MFN that emerged: (1) Global Alignment, (2) Local Protection, and (3) Access-Driven Equity. Rather than converging on a single global pricing paradigm, these three approaches turned into the federal policy framework ultimately leading to the introduction of GLOBE for Medicare Part B, GUARD for Medicare Part D, and GENEROUS for Medicaid.
Background
MFN policies rapidly evolved from a sentiment that Americans should not be paying more for prescription drugs to a policy framework aimed at implementing international reference pricing for Medicaid and Medicare. The key milestones include:
- May 12, 2025 — Executive Order “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients” directs agencies to pursue voluntary MFN commitments from manufacturers, with the threat of formal rulemaking if progress stalls.
- September 2025–August 2026 — The administration secures voluntary MFN pricing agreements with 26 manufacturers, covering an estimated 89–90% of the U.S. branded drug market, in exchange for relief from pharmaceutical tariffs and production commitments.
- November 6, 2025 — CMS unveils the voluntary GENEROUS Model, bringing MFN-style supplemental rebates to Medicaid.
- December 19, 2025 — CMS proposes the mandatory GLOBE (Part B) and GUARD (Part D) Models, alongside the voluntary, GLP-1-focused BALANCE Model.
- January 1, 2026 — TrumpRx.gov, a direct-to-consumer purchasing platform, launches, offering MFN-linked cash prices on drugs including GLP-1 and fertility medications.
- April 2, 2026 — An Executive Order on pharmaceutical imports ties tariff relief explicitly to MFN pricing and domestic manufacturing commitments.
- July 1, 2026 — The Medicare GLP-1 Bridge demonstration begins, offering a $50 flat monthly copay for anti-obesity medications, as an interim step toward the BALANCE Model.
- September 2026 — All 50 states, D.C., and Puerto Rico enroll in the GENEROUS Medicaid Model; the administration reports the steepest annual decline in prescription drug prices since 1963.
Global Alignment Gains Momentum
Governments continue seeking mechanisms to control healthcare spending, while payers are leveraging broader datasets to benchmark value and affordability across markets.
While a fully harmonized global pricing framework remains unlikely, the direction of travel is clear. Greater visibility into pricing and value assessments has reduced the flexibility companies historically relied upon to set market-specific prices. As a result, global coordination has become less of a strategic advantage and more of an operational necessity.
Mandatory in Spirit
Both Medicare MFN Models, Globe and Guard, are mandating the use of international reference pricing for qualifying single-source drugs and sole-source biologics. These programs attempt to incentivize manufacturers to submit reference pricing data but stop short of mandating it instead opting to rely on publicly available international pricing information when manufacturers do not proactively provide pricing.
Meanwhile, the Medicaid Model, Generous remains entirely voluntary and even though 26 manufacturers signed voluntary MFN agreements, almost all those manufacturers still took their regularly scheduled January 1st price increases.
This raises the question of how mandatory MFN initiatives will become. While the current White House administration has the appetite to utilize MFN policies to lower prescription prices, they may not have the operational means to implement a true international reference pricing approach in the current healthcare infrastructure.
Recommended Manufacturer Actions
Manufacturers Should Consider the Following:
- Gather internal international reference price points from the markets that are covered by GLOBE and GUARD
- Know what international reference pricing is publicly available and identify the gaps in publicly available information
- Identify which products could be covered under GLOBE, GUARD, and GENEROUS
Conclusion
While the next phase of the pricing debate is unlikely to focus solely on whether MFN-style policies should exist, launch pricing strategy will need to be a global conversation instead of setting product pricing in geographic silos. International reference pricing may not take over the price-setting practices for products in the US, but it will certainly be a factor.
The challenge for industry leaders will be navigating a future where global comparisons are unavoidable, local protections remain necessary, and expectations for patient access continue to grow.
Author
Megan has more than nine years of experience in the life sciences industry, specializing in Government Pricing (GP). She lead’s EVERSANA’s GP team and has a large range of experience in all areas related…
Heather Miller joined EVERSANA in 2024 as a Principal Analyst, bringing nearly a decade of specialized experience in pharmaceutical pricing strategy and compliance. Prior to joining EVERSANA, Heather spent eight years working with multiple…