Pharmaceutical companies have always operated under regulatory and market pressure. What is different now is the speed, scale, and simultaneity of the forces reshaping pharma economics. A wave of global policy changes, most prominently the Inflation Reduction Act (IRA), the EU Joint Clinical Assessment (JCA), and Most Favored Nation (MFN) reference pricing, but extending well beyond these, is not arriving sequentially. It is arriving all at once, and the cumulative effect is structural.

Together, these policies compress revenue windows, raise the evidentiary bar for reimbursement, increase data visibility across markets, and link pricing decisions across borders. Each would demand a serious strategic response on their own. Converging simultaneously, they create a multiplier effect that makes traditional, sequential planning cycles inadequate by design.

The implication is not simply that companies need better commercial strategies. It is that the most consequential decisions, those that determine whether an asset reaches patients with credible, defensible value, must now be made earlier in development than most organizations are currently structured to support. We call this decision velocity: the capacity to make high-stakes, cross-functionally integrated choices upstream, before the evidence is locked, the protocol is filed, or the pricing architecture is set.

Four value inflection points determine where value is built or lost across the development and commercialization lifecycle. The convergence of IRA, JCA, and MFN does not create new inflection points, it shifts when the decisions at each one must be made and raises the cost of getting them wrong.

The organizations best positioned to operate in this environment are what we call policy-adaptive enterprises: companies that have rebuilt how they govern, plan, and generate evidence around the reality that policy shapes value long before launch. They practice anticipatory strategy, designing for multiple policy futures rather than reacting to each change as it arrives. They govern cross-functionally, bringing clinical, HEOR, market access, regulatory, and commercial teams into shared decisions from early development. They apply portfolio-level thinking, recognizing that IRA, JCA, and MFN affect asset types differently and that indication sequencing, exclusivity timelines, and evidence requirements must be calibrated accordingly. And they invest in building a value story that payers, health technology assessors, and health systems can interrogate and accept, rather than one constructed at the negotiating table under time pressure.

The stakes extend beyond any individual asset or company. The ability to sustain pharmaceutical innovation under sustained fiscal pressure has direct consequences for future R&D investment, patient access, and the long-term viability of the global development ecosystem.

The policy convergence that changed everything

The case for bringing commercial thinking earlier in the development pathway is not new. What is genuinely new – and seismic – is the speed, scale, and simultaneity of the forces now reshaping pharma economics.

  • The IRA potentially compresses revenue horizons for high-spend drugs in the world’s largest market: nine years for small molecules, thirteen for biologics, before Medicare reimbursement caps come into play. NPV calculations must anticipate that a drug may eventually be selected for IRA price negotiations and be built on IRA-adjusted models from day one, with implications for indication sequencing, even viability.
  • The EU JCA has introduced a harmonized framework in which the clinical assessment is reflective of all Member States’ needs, leading to multiple decision problems that require more consideration and earlier planning built into clinical and real-world evidence generation plans. The JCA introduces a shift in strategic framing from market-by-market planning, to a pan-European evidence architecture. As rare disease assets become subject to JCA in 2028, there are some really important considerations that come into play in variability of country care pathways, comparator availability, and how to control for outcomes in single-arm studies.
  • The proposed MFN pricing framework varies between US Medicare and Medicaid as well as the countries that are included in the market basket, meaning there is a high level of uncertainty as to the specific impacts of implementation on US pricing.

Individually, each policy would demand a serious strategic response. Converging simultaneously, they create a multiplier effect that makes traditional sequential planning cycles structurally inadequate. This is the decision velocity challenge: the need to make high-stakes, cross-functional decisions earlier, faster, and with greater foresight than most organizations are currently structured to support.

“Commercial excellence cannot recover value that was never designed into an asset. If the evidence is lacking, the indication mis calibrated, or the pricing architecture broken, no amount of commercial muscle will fix it.”

Four inflection points: where value architecture is built or lost

The shift required is not incremental, it is a fundamental recalibration from a focus on optimizing access and commercial excellence to architecting value across the entire development lifecycle. Four inflection points mark where that value is created or permanently lost, and the convergence of IRA, JCA and MFN have direct impact on each of them:

1. Engage Early to Create the Path to Value

At the moment of target selection, decisions about indication choice and sequencing, portfolio balance, and development investment must now incorporate IRA horizon modelling, global reimbursement potential, and global pricing spillover analysis. The traditional “best science” approach – leading with innovation and building the commercial case later – is no longer sufficient. Policy impact must be integrated from target identification onward, with broader consideration of the longer-term development and commercialization strategy.

  • Emerging evidence suggests that the IRA is already shaping post-approval development decisions; a 2025 study (Zheng H, Patterson JA, Campbell JD. Health Affairs Scholar. 2025;3(8):qxad152) found a significant post-IRA decline in industry-sponsored post-approval oncology trials, with disproportionate reductions for small molecules. Whether this reflects a deliberate portfolio reprioritization of broader market dynamics remains an active area of research.

2. Define and Deliver the Optimal Development Strategy

This is where the most consequential and irreversible choices are made. It is even more essential that clinical protocols simultaneously serve dual masters: regulatory approval and HTA requirements. Evidence generation cannot be retrofitted post-development. New capabilities are required in earlier and iterative evidence planning supported by:

  • Early cross-functional collaboration with geographic input.  Local affiliate expertise,  historically brought in late, must now inform protocol design so organizations can anticipate how individual European countries will situate an asset within their specific care pathway context before trial design is locked. Early PICO scenario mapping is required to inform clinical and real-world evidence plans, and value positioning strategy.
  • Modular trial design — adaptive protocols that accommodate divergent requirements
  • Integrated evidence roadmaps that extend from approval through to long-term reimbursement defence, with iterative evidence planning in response to evolving HTA scenarios

A US biotech navigating simultaneous FDA and EMA regulatory pathways and JCA requirements aligned pivotal endpoints with JCA evidence needs in modular Phase III design, creating the flexibility needed to accommodate divergent requirements.

3. Configure the Optimal Go-to-Market Strategy

By the time an asset reaches commercial configuration, its market access parameters are largely determined by earlier choices. Commercial excellence cannot recover value that was never designed into an asset. If the evidence is lacking, the indication miscalibrated, or the pricing architecture broken, no amount of commercial muscle will fix it.

JCA submission planning should start early with anticipating the scope that the JCA would request, understanding gaps, and iterating evidence generation plans, supplementing clinical with real world evidence.

To mitigate consequences of MFN, companies should develop a truly global net pricing and access strategy, one that treats the US as part of a global whole, rather than the automatic anchor. This means undertaking scenario modelling of pricing spillovers across geographies, deliberate launch sequencing, and building local access structures.

  • One company managing pricing interconnectedness across more than 100 markets developed a structured approach to global launch sequencing, mapping price spillover scenarios across geographies and aligning indication strategy to a global access framework

4. Engage, Measure and Refine for Sustained Market Success

Value demonstration does not end at approval. IRA negotiations, separate JCA assessments for new indications, and ongoing payer scrutiny mean companies must maintain integrated evidence roadmaps that extend well beyond launch: this requires continuous value demonstration. Real-world evidence programs – planned during development, executed continuously post-approval – are how companies build the proof base needed to defend pricing over time and across negotiations.

  • A company preparing for future Medicare negotiation on a high-value rare disease asset built a comprehensive RWE program using predictive analytics to quantify healthcare system savings, positioning itself for negotiation from a foundation of demonstrated societal value rather than clinical trial data alone.

“The future will note be decided by how well companies launch products, but by how intelligently they navigate the inflection points that precede launch.”

Becoming a policy-adaptive enterprise

Succeeding in this environment is ultimately an organizational question, not just a strategic one.

The companies best equipped to navigate it share four defining characteristics.

  1. They practice anticipatory strategy: taking the upstream decisions to navigate downstream constraints, and planning for multiple futures rather than reacting to changes as they arrive.
  2. They operate with integrated governance:  breaking down functional and geographic silos so that clinical, medical, commercial, regulatory, market access, HEOR and real-world evidence teams make decisions together, early, rather than handing off sequentially.
  3. They apply portfolio-level thinking: recognizing that IRA, JCA, and MFN affect different asset types differently, and that indication sequencing, exclusivity timelines, and evidence requirements demand distinct strategies across a portfolio.
  4. They invest in narrative leadership: actively shaping how the value of their innovations is understood by payers, health technology assessors, and health systems, rather than allowing that narrative to be defined by others at the negotiation table.

What to do, now

  • Build IRA-adjusted NPV models from day one. While only a subset of high spend drugs are selected for IRA price negotiations, the uncertainty of selection is itself a planning variable. Indication sequencing and portfolio investment decisions must reflect the potential for compressed revenue windows, including the nine vs. thirteen-year distinction between small molecules and biologics, calibrated to your specific assets and portfolios.
  • Treat protocol design as global market access strategy. Evidence cannot be retrofitted; regulatory and HTA requirements must be designed in simultaneously, with adaptive clinical protocols designed to accommodate divergent PICO scenarios across countries, within a single study structure.
  • Map PICO scenarios before finalizing trial designs. Anticipating how each European country will evaluate your asset enables you to embed the necessary clinical flexibility before it is too late to do so. 
  • Restructure cross-functional governance for earlier integration. Clinical, medical, commercial, market access, HEOR, and RWE teams must be working together from Phase 2, or earlier. Local market understanding also needs to be engaged within that to anticipate PICO scenarios.
  • Develop integrated evidence roadmaps that begin during development. RWE programs planned before approval provide the credible, longitudinal data required for IRA negotiations, JCA assessments, and evolving payer demands.
  • Model pricing spillovers to inform a truly global launch strategy. Launch sequencing must reflect a global access strategy that considers patient need, pricing dynamics, and revenue across all markets – not default to US-first assumptions. Deliberate, evidence-based sequencing decisions should serve global access objectives.
  • Build toward becoming a policy-adaptive enterprise. Anticipatory strategy, integrated governance, portfolio-level thinking, and narrative leadership are the organizational characteristics that separate companies that thrive in volatility from those that are overtaken by it.

The companies that move first will define what comes next

The companies that navigate this environment most successfully will not necessarily be the largest or best resourced, they will be those that recognize the rules have changed and adapt before others do.

This is not a challenge that commercial excellence alone can solve. The policy pressures reshaping pharma economics – across IRA, JCA, MFN and beyond – do not respect functional boundaries, and neither can the response. Lumanity brings deep expertise across each of these critical inflection points. More importantly, we bring the integration across them: working with development and commercial teams as a connected partner, not a series of sequential workstreams, to build the value architecture that protects and grows asset value from early development through to sustained market success.