The Great Repricing: How Pharma Must Evolve for Three Diverging Payer Economies

December 12, 2025

The fracturing of the US drug market’s traditional model is forcing a demand for a strategic bifurcation to maintain profitability, compliance, and patient access in the decade ahead.

Building on my 2024 “Rise of Cash Pay and Direct-to-Patient (DTP)” and the 2025 “GTN Optimization” series, the 2026 theme—“The Great Repricing”—marks a new era of transformation. The US pharmaceutical market is undergoing a macro realignment in pricing and channel strategy as the traditional commercial insurance–driven model fractures into three competing payer economies.

In this first of six articles, we will examine the fragmenting market and its emerging payer realities. As presented at IntegriChain’s Access Insights Conference, the US drug market has splintered into three payer archetypes—commercial, government, and self-pay—each defined by distinct economics, incentives, and compliance risks.

From one center of gravity to three

For decades, the US pharmaceutical marketplace revolved around a single gravitational center: the commercial insurance model dominated by health plans and pharmacy benefit managers (PBMs). Manufacturers optimized rebates, access, and patient affordability through a formula that, while complex, was at least predictable.

That era is ending. Policy reform, economic pressure, and patient empowerment have fractured that reality into three distinct payer economies—commercial, government, and self-pay—each operating with its own pricing logic, regulatory constraints, and distribution ecosystem.

Government pricing is being reshaped by the Inflation Reduction Act (IRA), 340B expansion, and Medicaid’s uncapped rebate structure—redefining what “net price” truly means.
Commercial payers, under pressure for opaque rebate practices and aggressive utilization controls, are re-engineering formulary power and challenging manufacturer economics.
Self-pay has emerged as a parallel market driven by transparency, telehealth, and consumer demand for simplicity and affordability.

Manufacturers now stand at the intersection of these diverging systems—managing a new balancing act between compliance, profitability, and patient access. The old playbook of “one list price, one access strategy” is obsolete.

This six-part “Great Repricing” series will explore how each payer economy functions, how they collide, and how forward-thinking manufacturers can design integrated pricing and channel strategies that sustain both affordability and innovation in the decade ahead.

Signals of change

On Oct. 27, Cigna announced its intent to evolve into a more transparent commercial payer model, moving away from plan-sponsor pass-through rebates and even experimenting with self-pay and cash-based prescription models. While modest, it signals growing recognition that the market is changing beneath everyone’s feet.

These payer experiments come amid a regulatory tidal wave: most-favored nation (MFN) proposals, HRSA’s 340B rebate model approval, most-favored pricing (MFP) frameworks, wholesale acquisition cost (WAC) decreases, the removal of the Medicaid average manufacturer price cap, and capped price increases under Medicare Parts B and D. The final 2026 Physician Fee Schedule, announced on Oct. 31, added another layer of cost pressure.

Taken together, these forces suggest a tectonic shift in how manufacturers will think about pricing, market and channel segmentation, and patient access.

What will (and won’t) change

When assessing where manufacturers should evolve, it’s useful to start with what remains relatively stable:

Won’t: Cell and gene therapies, orphan/rare disease, and oncology medical benefit products are insulated from self-pay markets and generally protected from the same GTN compression affecting general and specialty medicines.
Will: General medicine products, by contrast, are deeply exposed—especially as they face a new wave of loss of exclusivity (LOE) and MFP rules.
Maybe: Specialty medicine is too early in its LOE wave to fully call this, but early indicators for oncology, immunology, and neurology (specifically multiple sclerosis) have some solid examples of the bifurcation across the three payer segments. We will need to watch this one.

The general medicine category has steadily shifted toward cash in generics since the concept was reintroduced in 2004 and accelerated after the 2017 patent cliff. Now, with another $180 billion general medicine cliff and a $230 billion specialty medicine cliff approaching, pricing pressure will intensify like never before.

When generics lose their edge

In past decades, the post-LOE dynamic was predictable: within one to three months of generic entry, brands lost roughly 90% of market share. But that simple model is breaking down.

Consider upcoming anticoagulants facing both MFP and LOE in the next 12 to 18 months. If these brands take proactive WAC reductions, the generic opportunity evaporates. The incentive for first-to-market authorized generics could collapse, reducing the value of that market to one-third of what it was in the mid-1990s.

Paradoxically, this may extend brand viability—a potential policy outcome favored by HHS, CMS, and the White House. By migrating brands toward self-pay models, manufacturers could bypass many of the traditional headwinds: coverage hurdles, utilization management, pharmacy abandonment, and affordability program costs.

Specialty medicine in transition

The specialty medicine space remains complex. There are examples of drugs that list for $120,000 annually and likely cost the plan sponsor half that after PBM negotiations, and the corresponding specialty generics might cost $20,000 to $30,000 a year. The same generic is available via self-pay/cash on Mark Cuban’s Cost Plus platform for $300 to $360 per year.

For patients with high deductibles, these self-pay/cash biosimilars and specialty generics offer a compelling alternative to insured access. As a result, even within specialty, cash pay is becoming a meaningful safety valve.

Identifying early movers

So, if you’re a manufacturer, how can you begin to apply these concepts to your portfolio? Our consulting work highlights several early cohorts most likely to experience the effects of repricing:

LOE/patent-expiry products: Facing dual pressure from a declining market and low-cost generic self-pay cash alternatives.
Low-volume general medicine brands: The ~4,400 products representing <2% of total retail prescriptions, usually with high GTN distortion.
Top 100 MFP-targeted products: Direct targets for government repricing and likely WAC reductions.
“Specialty-lite” brands: Mid-priced therapies struggling with coverage, aggressive utilization management, and pharmacy abandonment.

These categories illustrate how pricing realignment is no longer theoretical—it is underway.

The three overlapping economies

We can now visualize three concentric circles: commercial, government, and self-pay. Each overlaps, yet increasingly competes for the same products and patients.

Commercial markets are signaling they may disfavor brands that lower their WACs, as these lower WACs erode PBM, GPO, pharmacy, and distribution margins.
Government payers (Medicaid, 340B, VA, DoD, and Medicare) with statutory access to better pricing and ongoing penalties for high prices and price increases.
Self-pay becomes the refuge. When the market built for commercial and government insurance fails the patient and the script, this is the cleanest market path where patients, prescribers, and manufacturers can transact directly with fewer distortions.

These market dynamics are forcing manufacturers into new forecasting and planning models that include payer allocation, channel allocation, list-versus-net dynamics, patient access design, and compliance risk management, all operating simultaneously.

Rethinking compliance boundaries

Even concepts such as inducement are being reconsidered. Once the most taboo of all concepts, in a self-pay environment, those constraints dissolve. That opens creative new possibilities for affordability and loyalty models, though they must still align with consumer protection and fair competition laws.

The rise of cash-based channels challenges many traditional assumptions in pharma compliance, pricing, and access strategy. The industry must adapt its frameworks just as rapidly as it adapts its pricing models.

Forces driving the tension map

Looking ahead in this series, we’ll explore the tension map across four dimensions:

Policy pressure: IRA provisions, AMP cap repeal, transparency mandates, and emerging state affordability boards.
Market innovation: DTP enablement, telehealth integration, digital pharmacies, and cash-pay networks as insurance alternatives.
Patient demand: Rising deductibles and growing frustration with benefit design are fueling the shift toward direct access.
Provider alignment: Clinicians face their own administrative fatigue and are seeking simpler prescribing pathways.

All of this converges on the manufacturer’s core challenge: maintaining profitability and GTN integrity while navigating three divergent payer economies.

Looking ahead

This opening article aims to frame the scope of “The Great Repricing.” Over the coming year, we’ll dive deeper into:

The unraveling of the commercial insurance model.
The expanding reach of government pricing control.
The rise of the self-pay market and its ecosystem.
The evolution of list/WAC and net pricing structures.
The physical channels that will—or won’t—support each payer economy.

The path forward demands not just GTN optimization but strategic bifurcation—one in which manufacturers intentionally balance three economic systems that now coexist, compete, and increasingly define the US drug market.

About the Author

Bill Roth is General Manager and Managing Partner of IntegriChain’s consulting business, which includes Blue Fin Group, a strategy consulting company he started in 2001, and the IntegriChain advisory services business.