How MFN and Direct-to-Consumer Models Are Rewiring US Market Access

Globally, 2025 marked a shift from debating drug pricing policy to implementing it. Pricing pressure intensified, evidence expectations rose, and long-standing access models began to change amid political and fiscal realities. In Trinity’s webinar “Around the World in Market Access 2026: Global Trends Life Sciences Leaders Need to Watch,” the team examined emerging access dynamics across the US, Europe, China, and key Latin American and MENA markets, with the US section centering on how manufacturers now need to manage both Most Favored Nation (MFN) requirements and a growing direct-to-consumer (DTC) channel.

MFN Moves From Concept to Operational Reality

The most consequential US development is the operationalization of MFN across federal programs and channels. What started as an executive policy signal in President Trump’s current term has become a set of manufacturer agreements, CMS payment models, and the Trump RX federal DTC platform.

In August 2025, 17 large manufacturers received letters that set expectations:

• MFN pricing for existing products for Medicaid
• MFN pricing for all new launches across books of business
• Repatriation of increased foreign revenue into the US
• Direct-to-consumer and/or direct-to-business supply of high-volume, high-rebate drugs via Trump RX

Manufacturers responded with a similar playbook: MFN pricing commitments for Medicaid and new products, DTC participation for selected mature brands, and US investment pledges in exchange for at least some near-term tariff relief.

New CMS Models: GENEROUS, GLOBE, and GUARD

MFN expectations then took shape in three CMS payment models: GENEROUS for Medicaid (voluntary), GLOBE for Medicare Part B, and GUARD for Medicare Part D (both mandatory).

GLOBE and GUARD use two price-referencing methods:

• Method I uses the lowest country-level per unit price from reference markets, based on international price data.
• Method II uses a volume-weighted average of manufacturer net prices across reference markets, adjusted for purchasing power parity (PPP).

For GUARD, the effective benchmark is the greater of Method one or Method two. GENEROUS benchmarks off the second-lowest net price among reference markets and requires enrolled manufacturers to submit international reference price information.

Markets with PPP values close to the US create higher risk and less pricing flexibility. This is pushing manufacturers to rethink launch sequencing and ex‑US strategy. Traditional priority markets may now affect US Medicare and Medicaid pricing, which requires more deliberate scenario planning for both in‑line and pipeline products.

How US MFN Is Reshaping Ex-US Strategy

Manufacturers are reassessing ex-US strategies to manage MFN risk while protecting global value. Practical moves include:

• Strengthening clinical value stories ex-US to support HTA outcomes and pricing potential
• Exploring private or cash pay channels outside reimbursed price controls
• Reviewing ability to increase list price levels where regulations permit, especially if Method one will apply
• Using alternative and value-based contracting to make net price comparisons less straightforward
• Delaying or withdrawing launches in markets that could significantly impede US economics such that the global commercial business case is untenable
• Revisiting outsourced go-to-market models that no longer allow control over ex-US price decisions

The common thread is disciplined scenario planning across the portfolio, including a closer match between the evidence package and ex-US payer expectations, and a tighter link between US and ex-US pricing decisions.

Direct-to-Consumer Pricing Becomes a Durable Access Option

In parallel, manufacturer-led DTC models are expanding. MFN, the Inflation Reduction Act’s negotiated prices, and growth in obesity-related DTC channels are all contributing to this shift.

Offering MFN-aligned cash prices directly to patients, often below US list prices, helps manufacturers:

• Meet MFN expectations
• Reduce reliance on PBMs
• Create access routes for uninsured and underinsured patients

Eli Lilly (LillyDirect), Novo Nordisk (NovoCare), Pfizer (PfizerForAll), and Amgen (AmgenNow) have expanded their DTC platforms, while AstraZeneca and others are participating in Trump RX to offer cash prices at steep discounts from list. These initiatives, along with the federal Trump RX platform, aim to make net prices visible and available to “all American patients,” particularly those without adequate coverage.

Obesity treatments led the initial wave, but DTC approaches are expanding into other therapy areas, especially for mature brands, high-rebate categories, and products facing access friction. The DTC business model is also moving along an adoption curve, with early adopters now joined by fast followers, signaling broader industry acceptance. DTC prices serve as visible reference points for peers and payers and can influence reimbursement negotiations, so manufacturers need to monitor how these cash prices feed back into contract discussions. They also need to manage regulatory scrutiny of DTC telehealth platforms and guard against channel cannibalization by coordinating DTC and reimbursed strategies.

What Manufacturers Should Do Next

US market access in 2026 is shaped by the intersection of MFN and DTC. Companies need structured scenario planning for both MFN price referencing methods, closer alignment between US and ex-US choices, and clear governance for DTC offerings and telehealth partnerships. That planning should incorporate model scope, PPP-driven risk across reference markets, ex-US mitigation strategies, and the growing role of DTC channels as both an access route and a pricing signal.

To explore these themes in more detail, watch the replay of “Around the World in Market Access 2026: Global Trends Life Sciences Leaders Need to Watch.” Our third annual State of Global Market Access white paper, which expands on what was shared in the webinar, will be released soon, and you can sign up to receive it by visiting TrinityLifeSciences.com. Other blogs summarize the Europe, China, and Latin America/MENA sections of the webinar.

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Author: Brenna Liponis