US Healthcare System Strain & Innovation

MarcusAccess Brief. I'm Marcus, with Sara. Today we're looking at HCA's $1 billion profit warning from uninsured patients — this signals systemic US healthcare access challenges impacting drug reimbursement. Eisai and Biogen's subQ Leqembi approval — reformulation needs new HEOR analyses for real-world adherence. And Huyabio's Opdivo combo skin cancer milestone — novel mechanism requires comparative effectiveness against existing immunotherapies. Sara, where do you want to start?

SaraLet's start with HCA's profit warning. That $1 billion hit is just the beginning of what's coming.

MarcusHCA's profit warning is a clear signal that the US healthcare system is becoming financially unsustainable as uninsurance rates climb. This creates a direct pressure point on high-cost therapies, particularly those targeting vulnerable populations. HEOR teams must now model financial risk scenarios that account for both treatment costs and the likelihood of uncompensated care.

SaraI don't think that's right. The financial risk isn't just about treatment costs—it's about how payers will shift those costs to manufacturers through more aggressive value-based contracting. HCA's situation is just the canary in the coal mine for what will happen across the entire reimbursement landscape.

MarcusThat's a valid point about value-based contracting, but you're missing the fundamental issue here. When patients lack insurance, they don't access care at all, which means no treatment happens, regardless of contracting mechanisms. The real HEOR challenge is modeling the cost of delayed or forgone treatment, not just adjusting payment structures.

SaraDelayed treatment is exactly the point! When patients don't have insurance, they don't get diagnosed early, so when they finally do access care, they're in more advanced stages requiring more expensive interventions. That's where the cost pressure comes from—it's not just about uncompensated care, but about disease progression.

MarcusThere's evidence contradicting that position. Multiple studies have shown that even with delayed diagnosis, the overall cost trajectory for chronic diseases like diabetes or hypertension follows a relatively predictable path regardless of insurance status. The difference is in who bears the cost, not necessarily the total economic burden.

SaraThat's the obvious read but it ignores the social determinants of health. Uninsured populations are more likely to have comorbidities, less likely to have access to preventive care, and more likely to live in areas with limited healthcare resources. These factors create a multiplier effect on costs that simple economic models don't capture.

MarcusThose social determinants are real, but they're not new. What's new is the scale of uninsurance and its impact on hospital finances. The HCA figure of $1 billion is concrete evidence of systemic strain. HEOR teams need to incorporate this into their value propositions by demonstrating how their products can reduce overall system costs, not just drug costs.

SaraAnd that's where real-world evidence becomes critical. We need to show how our drugs can prevent complications that lead to expensive hospitalizations. But with rising uninsurance, generating that RWE becomes harder because we're losing the ability to track outcomes across the care continuum.

MarcusEisai and Biogen's approval of subcutaneous Leqembi represents a significant administration innovation for Alzheimer's treatment. This reformulation addresses a key barrier to adherence in a patient population often struggling with cognitive impairment. However, it creates a new HEOR imperative to demonstrate real-world effectiveness compared to the existing intravenous formulation.

SaraThe administration improvement is real, but we can't ignore the cost implications. Subcutaneous administration may be more convenient, but it doesn't necessarily equate to better outcomes. Payers will demand clear evidence that justifies any potential premium pricing for this reformulation.

MarcusThat's too narrow a framing. The value proposition isn't just about outcomes—it's about the total cost of care, including caregiver burden and healthcare resource utilization. The convenience factor may reduce hospital visits and caregiver time, which have significant economic value that traditional HEOR models often overlook.

SaraYou're missing the point here. The market access challenge isn't just about demonstrating value—it's about positioning this reformulation in the context of emerging GLP-1 Alzheimer's therapies that may offer both administration convenience and potential disease modification benefits. Leqembi's subcutaneous version is playing catch-up in a rapidly evolving landscape.

MarcusThat contradicts what we saw with the initial Leqembi launch. The real-world data showed that administration burden was a significant barrier to adherence, particularly in the elderly population. The subcutaneous formulation addresses this directly, which should translate to better persistence and potentially better outcomes. That's the HEOR story we need to tell.

SaraBut what about the evidence? We don't yet have head-to-head data comparing subQ to IV formulations in real-world settings. Without that, any claims about improved adherence or outcomes remain speculative. Payers will demand that evidence before considering any value-based contracting arrangements.

MarcusThe absence of head-to-head data doesn't negate the known barriers to IV administration in elderly patients with cognitive impairment. There's substantial evidence showing that complex administration regimens reduce adherence in this population. The HEOR challenge is to model the expected improvement in persistence and translate that into economic value.

SaraAnd we need to consider the competitive landscape. As GLP-1 Alzheimer's therapies emerge, they may offer oral administration with potentially better CNS penetration. The subcutaneous Leqembi, while an improvement, still faces the fundamental challenge of being an antibody-based therapy with limited CNS bioavailability. That's the HEOR reality we need to address.

MarcusHuyabio's positive Phase III data for their Opdivo combination in skin cancer represents a significant advancement in oncology treatment. The results validate a novel mechanism and generate pivotal evidence for both US and European submissions. From an HEOR perspective, this creates an opportunity to develop value propositions emphasizing survival gains and quality-of-life improvements in a competitive therapeutic landscape.

SaraSurvival gains are important, but in today's oncology market, we need more than that. With the rise of biosimilars and the IRA in the US, payers are demanding evidence of differentiation beyond just延长生存期. We need to demonstrate how this combination improves patient experience or reduces treatment burden compared to existing options.

MarcusThat's the obvious read but it ignores the methodological challenges in measuring quality of life in oncology patients. Many existing PRO instruments weren't designed to capture the nuances of combination therapy effects. The HEOR community needs to develop more sophisticated endpoints that truly reflect the patient experience with these novel regimens.

SaraI don't think that's right. The methodological challenges are real, but they're not insurmountable. What's missing is a clear understanding of what payers value most in this space. Is it progression-free survival? Overall survival? Quality-adjusted life years? Or something else entirely? Until we answer that question, our HEOR strategies will be misaligned with payer expectations.

MarcusThere's evidence contradicting that position. Multiple HTA assessments across Europe have consistently shown that payers value overall survival most highly, followed by quality of life metrics. The challenge is demonstrating statistically significant differences in these endpoints, which often requires larger or longer trials than companies are willing to conduct.

SaraAnd that's exactly the problem. With increasing pressure on development timelines and costs, companies are conducting smaller trials with shorter follow-up, making it harder to demonstrate meaningful differences in overall survival. The HEOR community needs to develop innovative trial designs that can generate robust evidence more efficiently.

SaraThe merger of Akero, Avere, and Nextcure signals a strategic shift toward long-acting biologics in the psoriasis space. This consolidation reflects industry recognition of the importance of adherence and persistence in chronic disease management. For HEOR teams, this creates an imperative to generate real-world evidence on long-term outcomes and compare these novel agents against existing IL-23 inhibitors.

MarcusLong-acting biologics are certainly attractive from an adherence perspective, but we can't ignore the cost implications. These therapies often come with higher price points, and with NICE's 2026 threshold updates, the cost-effectiveness bar is being raised. HEOR teams need to demonstrate that the adherence benefits translate into meaningful economic value.

SaraThat's too narrow a framing. The value proposition extends beyond simple adherence—it's about reducing the total cost of care by preventing disease flares and avoiding treatment switches. Long-acting biologics may have higher acquisition costs, but if they reduce the need for rescue therapies or hospitalizations, the overall economic argument becomes more compelling.

MarcusYou're missing the point here. The market access challenge isn't just about demonstrating value—it's about positioning these therapies in the context of biosimilar competition. As IL-23 inhibitors lose patent protection, biosimilar versions will drive down prices, making it harder for novel long-acting agents to justify premium pricing. The HEOR story needs to address this competitive reality.

SaraThat contradicts what we've seen in other therapeutic areas. Even with biosimilar competition, innovative therapies with clear differentiation can maintain premium pricing. The key is demonstrating meaningful differences in outcomes or patient experience that justify the cost. For long-acting biologics, the value proposition should focus on reduced treatment burden and improved quality of life.

MarcusThe absence of head-to-head data doesn't negate the potential benefits of reduced dosing frequency. There's substantial evidence showing that treatment burden significantly impacts adherence in chronic diseases. The HEOR challenge is to model the expected improvement in persistence and translate that into economic value, particularly for patients who struggle with complex treatment regimens.

SaraAnd we need to consider the US-specific challenges with the IRA. As more drugs become eligible for negotiation, the commercial landscape is shifting dramatically. Long-acting biologics in psoriasis will likely face negotiation pressure, so the HEOR case needs to demonstrate clear differentiation not just from existing branded therapies, but also from potential biosimilar competition.

MarcusICER's expansion of scientific advice services reflects a growing demand for early HEOR alignment to mitigate reimbursement risks. This trend mirrors the JCA scientific advice constraints in Europe but with a US-specific focus on value frameworks like equity adjustments. For global market access teams, this creates an opportunity to align HEOR strategies across jurisdictions while addressing jurisdiction-specific requirements.

SaraEarly alignment is certainly valuable, but we need to be realistic about what ICER can actually deliver. Their advice is often based on preliminary data and assumptions that may not hold up as the clinical program progresses. Companies need to approach ICER advice with a healthy dose of skepticism and not treat it as a guarantee of future reimbursement success.

MarcusThat's the obvious read but it ignores the strategic value of early engagement. Even if ICER's advice doesn't guarantee reimbursement success, it provides critical insights into payer expectations that can inform clinical trial design and HEOR strategy development. The process itself is valuable, regardless of the specific recommendations.

SaraI don't think that's right. The strategic value is overstated. ICER's advice is often based on incomplete data and may not reflect the final evidence package that will be submitted. Companies that rely too heavily on preliminary advice may find themselves in difficult positions when the final data doesn't align with earlier assumptions.

MarcusThere's evidence contradicting that position. Multiple studies have shown that companies that engage early with HTA bodies like ICER have higher success rates in reimbursement decisions. The key is not to treat ICER advice as definitive, but to use it as one input among many in developing a comprehensive HEOR strategy.

SaraAnd what about the resource implications? Engaging with ICER requires significant investment in data preparation and analysis, which may not be feasible for smaller companies or those with limited HEOR resources. The expansion of scientific advice services may exacerbate existing disparities in market access capabilities between large and small companies.

MarcusThat's a valid point about resource implications, but it's not unique to ICER. All HTA engagement requires resources, and the trend toward early alignment is global. The HEOR community needs to develop more efficient methods for generating the evidence needed for early engagement, including leveraging RWE and innovative trial designs.

SaraUltimately, the expansion of scientific advice services reflects a broader shift toward value-based pricing. Companies need to adapt their HEOR strategies to engage early and often with payers, demonstrating clear differentiation and value throughout the product lifecycle. This isn't just about securing initial reimbursement—it's about maintaining market access as the evidence landscape evolves.

MarcusThe convergence of US healthcare system strain, administration innovations, and competitive oncology landscapes is reshaping HEOR priorities. We need more sophisticated models that capture total system costs and patient experience.

SaraEarly payer engagement through scientific advice will be critical, but companies must balance this with realistic expectations about what preliminary data can actually tell us about future reimbursement prospects.