The pharmaceutical pricing landscape changed significantly in 2025. Most-Favored-Nation pricing mandates and the Inflation Reduction Act’s drug negotiation rules are reshaping how manufacturers price and distribute medicines in the U.S., increasing pricing pressure and oversight. As a result, manufacturers must rethink access models while maintaining compliance and patient affordability.

Direct-to-Patient (DTP) programs offer a practical response. DTP pricing strategies give manufacturers greater control over distribution and clearer visibility into patient costs. By aligning pricing and access earlier, DTP models reduce delays, limit leakage and support consistent compliance under MFN and IRA requirements.

Understanding the MFN Regulatory Framework

In May 2025, the Executive Order titled “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients” marked a major change in U.S. pharmaceutical pricing policy. The order directs the Department of Health and Human Services (HHS) to ensure Americans can access prescription drugs at MFN prices, defined as the lowest prices offered in comparable developed countries.

To operationalize this policy, HHS established specific requirements manufacturers must meet:

• MFN price benchmark: U.S. prices must match the lowest price offered in any OECD country with a GDP per capita at least 60% of U.S. GDP per capita.
  
  

• Products in scope: The requirement applies to brand-name drugs without generic or biosimilar competition.
  
  

• Market coverage: MFN pricing must be applied across all markets, not limited to federal programs.

By late 2025, several major pharmaceutical manufacturers had entered MFN pricing agreements with the administration, reflecting increasing pressure to comply. Pfizer was the first to reach an agreement in September 2025, followed by AstraZeneca, EMD Serono, Novo Nordisk and Eli Lilly. These agreements require manufacturers to extend MFN pricing to all state Medicaid programs and ensure that new drug launches align with prices offered in other developed markets.

Why MFN Creates Direct Distribution Incentives

The MFN framework creates a strong incentive for DTP distribution by requiring pricing transparency that traditional PBM rebate structures do not easily support. In conventional pharmacy benefit channels, confidential rebates create a gap between list and net prices, making it difficult to verify that U.S. patients are receiving prices aligned with the lowest international rates.

DTP programs address this challenge by establishing a clear, published transaction price. When manufacturers sell directly to patients at a defined cash price, pricing visibility is immediate and verifiable. The Executive Order explicitly directs HHS to facilitate direct-to-consumer purchasing programs that offer medications at MFN prices, effectively positioning DTP distribution as a practical pathway for regulatory compliance.

The IRA Drug Negotiation Landscape

While MFN focuses on international price alignment, the Inflation Reduction Act addresses domestic drug pricing through Medicare’s expanded negotiation authority. The IRA established the Medicare Drug Price Negotiation Program, which authorizes the Centers for Medicare & Medicaid Services (CMS) to negotiate Maximum Fair Prices (MFPs) for selected high-expenditure, single-source drugs.

The program follows a phased, multi-year rollout:

• 2024: CMS completed negotiations for the first 10 Medicare Part D drugs, with MFPs scheduled to take effect on January 1, 2026.
  
  

• 2025: An additional 15 drugs were selected for the second negotiation cycle, including widely used GLP-1 medications Ozempic and Wegovy, with negotiated prices effective in 2027.
  
  

• Ongoing expansion: The program will continue to scale, with 15 drugs selected annually for 2028 and 20 drugs selected each year thereafter.

MFP Effectuation and Compliance Requirements

Once a Maximum Fair Price is negotiated, manufacturers must effectuate that price across all Medicare transactions. CMS has established detailed guidance on how manufacturers must pass through MFPs to dispensers for eligible patients, including the development of a “Medicare Transaction Facilitator” infrastructure.

These effectuation requirements create operational complexity. Manufacturers must verify patient eligibility for negotiated prices, ensure correct pricing at the point of dispensation, and maintain audit trails demonstrating compliance. DTP programs can simplify this process by consolidating eligibility verification, pricing application, and fulfillment under manufacturer control.

How DTP Programs Enable Pricing Compliance

DTP programs help manufacturers address the overlapping compliance challenges created by MFN pricing requirements and the IRA. By improving pricing transparency, strengthening eligibility controls, and aligning with existing regulatory exclusions, DTP models provide a practical pathway to execute compliant pricing strategies at scale.

Bypassing PBM Rebate Complexity

The traditional pharmaceutical distribution model depends on PBM-negotiated rebates, where manufacturers establish higher list prices and offer confidential, percentage-based concessions in exchange for formulary placement. This structure can encourage inflated list prices and limit visibility into true transaction values, making net pricing difficult to assess.

DTP programs remove this opacity by enabling transparent, published cash pricing. Through manufacturer portals and platforms such as TrumpRx.gov, medications like Ozempic and Wegovy are offered at approximately $350 per month, compared to list prices exceeding $1,000. These clear transaction prices can be directly compared with international reference prices to support MFN compliance.

Streamlining Eligibility Verification

Determining which patients qualify for discounted pricing is essential under both MFN and IRA frameworks, although the type of verification differs. 

Under the IRA, only Medicare beneficiaries are eligible for negotiated Maximum Fair Prices, so manufacturers must confirm Medicare status. MFN‑linked DTP programs are often cash‑pay offers open to any patient with a valid prescription, but manufacturers still need to verify that the patient has a prescription and is paying cash rather than using insurance.

DTP platforms can handle both types of checks, verifying Medicare eligibility for IRA pricing or confirming prescription status and no‑insurance attestations for cash‑pay MFN offers, while creating an audit trail for compliance.

DTP platforms allow manufacturers to manage eligibility verification directly within the ordering workflow. This reduces reliance on third-party systems, ensures correct pricing is applied to the right patients, and creates auditable documentation to support regulatory review.

Supporting Best Price Compliance

Manufacturers participating in Medicaid must comply with Best Price reporting requirements, ensuring Medicaid receives pricing at least as favorable as that of other purchasers. While offering low DTP cash prices could raise concerns, regulatory exclusions may apply. Best Price rules exclude manufacturer-sponsored drug discount card programs and direct patient assistance programs when the full discount passes to the consumer, and no intermediary receives concessions. 

Properly structured DTP programs can fall within these exclusions, allowing competitive pricing without triggering additional Medicaid rebate obligations. Additionally, value-based purchasing arrangements provide flexibility by allowing multiple reported prices tied to outcomes, with states opting in to participate.

The Role of Benefits Verification Automation

As manufacturers use DTP programs to meet MFN and IRA pricing requirements, benefits verification automation becomes essential infrastructure not just an operational tool. MFN and IRA compliance both depend on applying the right price to the right patient at the right time. BV automation enables this precision at scale by validating coverage, eligibility, and pricing pathways before fulfillment occurs.

In practice, benefits verification automation supports DTP pricing compliance in several key ways:

Real-Time Eligibility Determination

Automated BV platforms verify insurance coverage, benefit design, deductibles, copayments, and coverage status in near real time. This enables DTP programs to immediately determine whether a patient qualifies for IRA-negotiated MFPs, manufacturer assistance programs, or MFN-aligned cash pricing.

Reducing Administrative Delays

Automation replaces manual phone calls and slow prior authorization workflows with instant eligibility responses. By returning results in seconds, BV systems improve speed to therapy and reduce access friction, aligning with the patient access objectives of both MFN and IRA policies.

Supporting Compliance Documentation

BV automation generates a clear audit trail of eligibility decisions. This documentation helps demonstrate that discounted pricing was applied correctly and only to eligible patients, supporting regulatory audits related to MFN and IRA compliance.

Integration with DTP Fulfillment

Advanced BV solutions integrate directly with dispensing and fulfillment systems. Once eligibility is confirmed, pricing is automatically applied during ordering, reducing manual handoffs and minimizing the risk of pricing errors.

Monitoring Coverage Changes

Because insurance coverage can change over time, verification automation continuously monitors eligibility and flags changes that may affect pricing qualification. This ensures ongoing compliance rather than relying solely on one-time verification.

Strategic Considerations for DTP Implementation

Manufacturers evaluating DTP strategies in response to MFN and IRA requirements should consider several practical factors. While DTP programs offer greater pricing transparency and operational control, successful implementation depends on thoughtful infrastructure planning, channel coordination, and market awareness.

Infrastructure Requirements

DTP programs require significant operational capabilities, including telehealth partnerships for prescription origination, licensed pharmacy operations or dispensing partnerships, logistics for home delivery, and technology platforms that support ordering, benefits verification, and fulfillment. Although these investments can be substantial, they provide manufacturers with greater control over the patient experience and pricing execution than traditional distribution models.

Industry adoption reflects this shift. Manufacturers such as Eli Lilly, AstraZeneca, Amgen, Bristol Myers Squibb, Novartis, and Boehringer Ingelheim have moved from limited pilots to visible consumer-facing platforms that combine cash-pay discounts with telehealth and delivery services.

Balancing Channels

DTP programs do not need to replace traditional pharmacy distribution entirely. Many manufacturers adopt hybrid models, using DTP for specific products or patient populations while continuing to rely on conventional channels for others. 

The critical consideration is ensuring DTP pricing aligns with MFN requirements and does not create conflicts across channels.

PBM Relationships

As DTP programs expand, PBM influence may shift, affecting broader market dynamics. Manufacturers should expect competitive responses, including enhanced specialty pharmacy offerings or new contracting approaches. 

As distribution models continue to evolve, the long-term structure of manufacturer-PBM relationships remains an important strategic consideration.

Designing for the Next Phase of Pricing Oversight

Looking ahead, MFN and IRA policies are likely to accelerate the shift toward pricing models that prioritize transparency, control, and verifiable compliance. As regulatory scrutiny increases, manufacturers will need access strategies that can reliably apply the right price to the right patient while withstanding audit and oversight.

Direct-to-patient programs, supported by automation and integrated verification, are positioned to become a core component of that future state. Rather than a temporary workaround, DTP pricing strategies are emerging as durable infrastructure for navigating ongoing policy change while preserving patient access and affordability.

FAQs

How do MFN and IRA timelines affect near-term compliance risk?

MFN and IRA policies are moving from policy design to enforcement. As negotiated prices take effect and additional drugs enter selection cycles, manufacturers face increasing audit scrutiny. Delayed readiness can expose gaps in eligibility application, pricing execution, and documentation, raising regulatory and operational risk in the near term.

Can DTP programs launch without disrupting existing distribution channels?

Yes. Manufacturers can deploy DTP programs for specific drugs, populations, or access scenarios while maintaining traditional channels elsewhere. When structured carefully, DTP complements existing distribution by addressing pricing-sensitive or high-risk compliance areas without forcing a full channel replacement or immediate market disruption.

How do CMS audit expectations differ between MFN and IRA programs?

MFN audits focus on price comparability and transaction transparency, while IRA audits emphasize eligibility accuracy and correct application of negotiated MFPs. Both require defensible documentation. Manufacturers must demonstrate not only correct pricing but also consistent, rule-based application across eligible patients and transactions.

Which internal teams must align to execute compliant DTP strategies?

Successful DTP execution requires coordination across market access, legal, compliance, IT, pharmacy operations, and patient services. Misalignment between these teams can create pricing inconsistencies or audit exposure. A centralized platform helps unify policy, technology, and operational workflows under a single compliance framework.

How does DTP infrastructure support future drug pricing policy changes?

DTP infrastructure provides flexibility to adapt as pricing policies evolve. By centralizing eligibility logic, pricing controls, and fulfillment workflows, manufacturers can respond quickly to new negotiation programs, expanded drug selections, or revised eligibility rules without rebuilding distribution or access systems from scratch.

What metrics should executives track to measure DTP compliance success?

Key metrics include eligibility accuracy rates, time-to-therapy, pricing error frequency, audit exception rates, and patient affordability outcomes. Tracking these indicators helps leadership assess whether DTP programs are improving compliance execution while delivering faster, more predictable patient access.