US Access Shifts: Leqembi, PBMs, and Early HEOR Strategy

MarcusWelcome to the Access Brief — your daily briefing on what's moving in HEOR, HTA, and market access. I'm Marcus, and it's great to have you with us today.

SaraAnd I'm Sara. Always good to be here — and I'll say, today's topics are particularly timely, given the churn in the US market.

MarcusSame here. We're looking at HCA's profit warning — a clear signal of access erosion in the US healthcare system. Then the subcutaneous Leqembi approval and its HEOR implications. Also, the FTC settlement with CVS Caremark over insulin pricing, which could reshape PBM practices. And ICER's expansion of early-phase scientific advice.

SaraThat second one about Leqembi is interesting — the shift to subcutaneous administration really changes the value equation for Alzheimer's, especially when you consider caregiver burden and real-world adherence.

MarcusExactly. Let's get into it.

MarcusLet's start with HCA's profit warning. The largest for-profit hospital chain in the U.S. just flagged significant financial pressure, citing increased uncompensated care and rising costs. This isn't just about hospitals; it's a symptom of broader access challenges in the U.S. healthcare system. When major hospital systems struggle, it often translates to tighter budgets for pharmaceuticals and medical devices.

SaraThat's one read — but I'd frame it slightly differently. The key here is the "uncompensated care" piece. HCA is seeing more uninsured and underinsured patients, which directly impacts their ability to negotiate drug prices. For payers, this signals potential cost-shifting and higher overall system costs that could spill over into formulary decisions.

MarcusWhat strikes me about that is the timing. We're in a period of high inflation and labor shortages, but the profit warning specifically points to uncompensated care as a driver. That suggests the safety net is fraying, and hospitals are absorbing costs that might have been covered by public payers in the past. This could lead to more aggressive formulary management.

SaraThat's fair, though I think payers would see it differently. They're already facing budget pressures from high-cost drugs and now they have to absorb more uncompensated care. The opportunity cost here is huge — every dollar spent on uncompensated care is a dollar not spent on innovative therapies.

MarcusThat connects to something I keep coming back to: the sustainability of the U.S. healthcare system. If hospitals are losing money, they might cut back on services or demand deeper discounts from manufacturers. This could create a vicious cycle where access is eroded not just by payer decisions but by the financial health of the delivery system.

SaraExactly. And for manufacturers, this means more pressure on pricing and reimbursement, especially for drugs that are seen as non-essential or have high budget impact. It's a tough environment for market access teams.

SaraShifting gears to the subcutaneous Leqembi approval. The FDA approved the subcutaneous formulation, which reduces infusion time from 2.5 hours to about 5 minutes. This is a significant improvement in patient experience and could expand access for those who struggle with intravenous infusions.

MarcusThat's one read — but I'd push back slightly on the access implications. The subQ formulation is approved for the same indication as the IV version, but it comes with a boxed warning for ARIA. The real question is whether the convenience justifies the risk, especially given the drug's modest efficacy and high cost. From a payer perspective, the value proposition isn't immediately clear.

SaraI wonder if that's the full picture though. The HEOR implications go beyond cost-effectiveness. The reduction in infusion time could lead to better adherence and lower caregiver burden. We might see real-world evidence studies focusing on quality of life and caregiver time, which are harder to capture in traditional trials.

MarcusThat's a fair point. The patient experience is critical, and subQ administration could open the door to treating patients who were previously unable to tolerate IV infusions. But the budget impact remains a concern. Even with improved adherence, the drug's cost is substantial, and payers will need robust evidence to justify it in formularies.

SaraWhat's striking here is the shift in evidence generation. We're moving beyond traditional endpoints to capture real-world outcomes. Manufacturers will need to invest in post-marketing studies that demonstrate the value of the subQ formulation in everyday settings. This could set a precedent for other neurodegenerative drugs.

MarcusAnd that's where it gets tricky. Real-world evidence for Alzheimer's is challenging because of the slow disease progression and confounding factors. But if the subQ version improves adherence, we might see better long-term outcomes that support value. It's a story worth watching.

MarcusNow, the FTC settlement with CVS Caremark over insulin pricing. The FTC alleged anti-competitive practices, including spread pricing and rebate structures that inflated insulin costs. The settlement requires CVS to change its practices and pay a fine. This is a significant development for the insulin market and PBM practices.

SaraThat's one read — but I'd frame it slightly differently. The key here is the focus on anti-competitive behavior. The FTC is sending a strong signal that PBMs cannot use their market power to extract excessive rebates at the expense of patients. For payers, this could lead to more transparent pricing and lower net costs for insulin.

MarcusWhat strikes me about that is the precedent it sets. Insulin has been a poster child for drug pricing issues, but the settlement could extend to other high-cost, essential drugs. If PBMs are forced to change their rebate structures, we might see a shift toward more value-based pricing and less gaming of the system.

SaraThat's fair, though I think the impact on access is mixed. While the settlement aims to lower out-of-pocket costs for patients, it could also reduce rebates that PBMs use to negotiate lower list prices. The net effect on formularies remains to be seen. Payers might face higher costs if the rebate model changes.

MarcusThat connects to something I keep coming back to: the complexity of the PBM ecosystem. This settlement could lead to more direct contracting between manufacturers and PBMs, bypassing some of the middlemen. It might also encourage more use of biosimilars and alternative payment models for insulin and other drugs.

SaraExactly. And for manufacturers, this means rethinking how they engage with PBMs. The era of opaque rebate structures might be ending, and we could see more emphasis on value-based contracts and transparent pricing. It's a significant shift in the market dynamics.

SaraFinally, ICER expanded its early-phase scientific advice program to include Phase I and II trials. This move aims to de-risk development by aligning evidence generation with HTA needs from the outset. It's a significant shift in how companies approach HEOR evidence strategy.

MarcusThat's one read — but I'd push back slightly on the de-risking claim. Early-phase trials are inherently uncertain, and HTA bodies like NICE have historically focused on late-phase data. The challenge is whether ICER can provide meaningful guidance at such an early stage without compromising the integrity of the evidence.

SaraI wonder if that's the full picture though. The expansion reflects a recognition that evidence generation needs to start earlier, especially for novel mechanisms and ultra-orphan drugs. By engaging with ICER in Phase I and II, companies can design trials that generate data relevant to HTA assessments, potentially reducing the risk of late-stage failures.

MarcusThat's a fair point. The timing is critical. If companies can incorporate HTA requirements early, they might avoid costly pivots later. But the practicality is questionable. Phase I and II trials are small and often focus on safety and efficacy, not the real-world outcomes that HTA bodies value.

SaraWhat's striking here is the evolution of HEOR strategy. This expansion could lead to more adaptive trial designs and real-world evidence integration from the start. It might also encourage more collaboration between industry and HTA bodies, which is a positive trend for the field.

MarcusAnd that's where it gets interesting. If ICER's early advice becomes a standard part of development, we might see a shift toward more evidence-based decision-making earlier in the pipeline. But it remains to be seen how widely adopted this will be and whether HTA bodies will truly value early-phase data.

SaraA lot to think about today. I'll be watching how the HCA profit warning impacts drug pricing negotiations and whether it signals a broader shift in US healthcare access.

MarcusSame — and for me the thread running through today is the evolution of evidence generation. From Leqembi's subQ formulation to ICER's early-phase advice, we're seeing a push toward more patient-centric and timely evidence.

SaraThanks so much for listening — really glad you're here with us.

MarcusWe'll be back tomorrow. Show notes and transcripts at outcomes-analytica.no. See you then.

SaraThanks for listening — see you tomorrow.

MarcusBack tomorrow on Access Brief. Show notes at outcomes-analytica.no.