We’ve entered a new era in pharmaceutical commercialization—an era shaped by regulatory upheaval, commercial pressures, and intensifying complexity across gross-to-net dynamics. As experts who’ve spent a combined 45+ years in this industry, we’ve seen the net revenue landscape transform significantly in just the last five years. In our recent webinar, we explored how these dynamics are reshaping net revenue modeling and how leading manufacturers can respond.

Understanding Today’s Landscape: The Revenue Pressure Cooker

Let’s start by acknowledging a reality: the “gross-to-net bubble” continues to swell. Many predict it may burst by 2030, and it’s becoming a central theme across industry discourse—including our own Access Insights Conference. But what’s really happening in 2025 and what’s driving this bubble today?

The persistent growth in 340B discounts is a major factor. From 2019 to 2022, we saw a marked increase in 340B’s share of the gross-to-net delta. While 2023 brought a slight stabilization, the real question is whether this is a temporary reprieve. Entities and providers are adapting to restrictions and still finding ways to maximize 340B savings. With tactics like aggressive use of contract pharmacies, patient definitions, and oncology aggregators acquiring local institutions, the complexities—and risks—only continue to multiply.

But 340B is just one part of the net revenue “pressure cooker.” We’ve identified over a dozen converging forces impacting manufacturers from all angles, including:

• Vertical integration transforming how prescribing and dispensing decisions are made; pharmacies and provider practices are increasingly owned by payer-controlled entities like Optum.
• Shift in decision-making authority from individual providers to integrated networks, meaning prescriptions may be redirected, substituted, or blocked altogether.
• Medicaid cuts and supplemental state negotiations creating variability and uncertainty in coverage and reimbursement.
• Pressure to maintain access while navigating increasingly competitive formularies and rising rebate burdens.
• Need for highly tailored modeling strategies specific to product archetypes, market channels, and payer dynamics.
• Upstream decisions in contracts, pricing, distribution, and packaging having direct impact on downstream net revenue performance.

Modeling for Insight and Action: Key Strategies for Optimization

Net revenue modeling has never been more critical—or more complex. Manufacturers are no longer just forecasting; they’re scenario-planning across commercial, legislative, and patient-access dimensions. At IntegriChain, we see this shift manifesting in several ways.

First, modeling now starts much earlier in the product lifecycle. It’s no longer sufficient to build your gross-to-net plan six months pre-launch. We’re helping manufacturers model as early as Phase II, using deep analogs and scenario frameworks to anticipate packaging needs, potential vial wastage rebates, or which payer channel—pharmacy or medical benefit—will dominate. These early insights can be the difference between margin erosion and strategic success.

Equally important is the understanding that a price increase doesn’t always result in net revenue growth. We’ve modeled scenarios where a 3% price increase actually outperformed a 6% or 9% increase in terms of net revenue. The reason? Inflationary rebates across Medicare Part B, Part D, Medicaid, and commercial contracts. These cumulative penalties often negate the top-line gain, and in some cases, even reduce net revenue. This requires a fundamental mindset shift across leadership teams. Price is no longer a blunt instrument for growth—it’s a lever that must be modeled and measured for its downstream implications.

We’re also seeing a surge in strategic modeling around Medicare’s Inflation Reduction Act (IRA). Whether it’s Part D redesign, MFP negotiations, or inflation penalties, IRA’s provisions are rewriting the playbook on revenue forecasting. We’ve supported clients who, through precise modeling, identified over-accruals as high as $80 million, and others who discovered $50 million in potential best price savings by evaluating alternative methodologies.

Another area gaining traction is the game-theory modeling of payer and provider economics. Especially for Part B drugs, understanding your ASP recovery, competitor positioning, and net recovery at the provider level is vital. The same goes for pharmacy benefit drugs: if a competitor is phasing into IRA discounts while your product is not, payers may prefer the competitor simply due to the rebate economics. Without modeling the net benefit to all stakeholders in your therapeutic class, you risk being blindsided.

From Complexity to Clarity: The Path Forward

As we guide our clients through these challenges, the core theme we emphasize is this: net revenue modeling is no longer a back-office function—it’s a strategic driver of enterprise value.

We see successful manufacturers taking a finance-and-compliance-first approach. Gone are the days where commercial teams drove strategy and finance teams reacted. Today, the financial impact of a price or contracting decision must be modeled before the strategy is finalized. This requires tighter collaboration across market access, trade, government pricing, and revenue management teams.

At IntegriChain, we’ve developed frameworks to help manufacturers align on a single source of truth for forecasting, scenario analysis, and reporting. We advocate for centralized risk-based modeling that captures payer bids, 340B eligibility, wholesaler admin fees, vertical integration impacts, and evolving legislation. These models must be dynamic—able to ingest updated data, legislation, or payer actions and instantly reveal the downstream financial impact.

As case studies show, the ROI of this work is tangible. Whether saving tens of millions through smarter best price calculations, optimizing launch sequencing to avoid liabilities, or redirecting distribution strategies to avoid high admin fees, manufacturers are using modeling to not only protect margin—but create it.

Ultimately, every product’s gross-to-net story is different. A specialty light drug launching through limited distribution has very different challenges than a high-volume, retail generic. That’s why modeling must be tailored—by product archetype, payer mix, pricing strategy, and market conditions.

This is not the time to rely on static spreadsheets or legacy assumptions. It’s time to embrace dynamic modeling, cross-functional strategy, and proactive planning. At IntegriChain, we’re proud to help our clients move from reactive analysis to strategic optimization. Because in this environment, clarity is power—and modeling is how you get there.

Let us help you think differently about gross-to-net. Join us at our upcoming Access Insights Conference this October and contact our Sales team for more information.