Overview of Market Access and Pricing Requirements in Europe

In the EU4 countries (France, Germany, Italy, Spain) and the United Kingdom (UK), the global value dossier and budget impact model are generally mandatory and/or relevant for diagnostic radiopharmaceuticals, as they are for other innovations. Based on our experience, payers recommend the cost-effectiveness model enriched with real-world evidence (RWE) to negotiate a higher price, particularly in Spain and Italy due to their budget-driven mindset.

The Health Economics and Outcomes Research (HEOR) requirements for diagnostic radiopharmaceuticals differ among the EU4 countries:

• Not mandatory but relevant for price negotiations in France, Germany and the UK
• Budget impact model is mandatory in national evaluations in Spain and Italy
• Cost-effectiveness model is strongly recommended to justify a higher price in Spain and Italy
• RWE is not mandatory in any of these countries but can help demonstrate the long-term impact on outcomes and ensure sustainable pricing

Health Technology Assessment (HTA) and Pricing Negotiation

Premium prices are generally perceived as the main barrier for commercial radiopharmaceuticals’ penetration rate, mostly in those situations where in-house production activities are well established.

EU4 and UK Markets

The HTA requirements for diagnostic radiopharmaceuticals differ among countries:

• Mandatory national HTA in France or therapeutic positioning report in Spain
• Upon request, national HTAs in Italy and the UK
• National HTAs in Germany are not expected, as the Gemeinsamer Bundesausschuss/Federal Joint Committee does not currently evaluate diagnostic radiopharmaceuticals, unless they serve as companion diagnostics (e.g., ongoing process for Locametz^® (68Gallium-Gozetotide)¹ as companion diagnostics of therapeutic radiopharmaceutical Pluvicto^® (177Lutetium-Vipivotide Tetraxetan)²).

Even if diagnostic performance and coverage of the unmet need are clearly acknowledged by the payers, the current evaluation criteria pose a challenge in the payer assessment of the added clinical value in Germany, France, Italy, and the UK.

On the price side, negotiations are generally anchored to the price of available options (even in-house production, where applicable) and pressured by national tariffs or by healthcare budgets.  Learn more about the variations between countries in the article Funding and Procurement Trends in Radiopharmaceuticals. The target population, unmet need, and economic evidence (i.e., HEOR models) are also relevant drivers for price setting in EU4 and UK markets.

Nordic Market

In the Nordics (Sweden, Norway, and Denmark), diagnostic radiopharmaceuticals are considered inpatient drugs. Generally, inpatient drugs do not undergo national HTA procedure unless they are high-cost innovative drugs.

No diagnostic radiopharmaceuticals had undergone an HTA in the Nordics at the time this article was published. HTAs are available only for therapeutic radiopharmaceuticals like Pluvicto^®2 and Lutathera^®3 in the Nordics, and Xofigo^®4 in Norway. Norway is the only country that requires a formal maximum price registration at the national level.

Baltic Market

In the Baltics (Latvia and Lithuania), radiopharmaceuticals are considered outpatient drugs. Diagnostic radiopharmaceuticals have undergone an HTA process in Lithuania, although the assessment is not public.

Challenges in Market Access and Pricing

Companies seeking to bring diagnostic radiopharmaceuticals to market face several significant market access and pricing challenges. These challenges, discussed in more details below, include a lack of infrastructure, both for production and provision of nuclear medicine services; supply chain complexity; the innovative nature of commercial products vs. in-house; and a lack of transparency around HTAs. 

The first challenge is that not all markets have the necessary infrastructure, such as cyclotrons and PET facilities, to meet radiopharmaceutical demand. For in-house radiolabeling, additional infrastructure, like generators, is needed to obtain the final ready-to-use product (e.g., 68Gallium-PSMA). Consequently, these infrastructure limitations restrict the ability of companies to scale sales in this market and meet the growing demand for PET imaging. Denmark is the most advanced market in terms of infrastructure for radiopharmaceutical production, followed by France.

In addition, many health centers and hospitals lack the capacity to host a radiopharmacy unit that can provide nuclear medicine services, creating a reliance on centralized radiopharmacies that supply multiple facilities. Companies must cope with shipping costs, potential delays, and supply chain bottlenecks. But this also presents an opportunity for radiolabeling of commercial solutions as a value-added service that companies can provide to those centers without radiopharmacies. The short half-life of radiopharmaceuticals requires rapid and timely supply. But there are many supply chain complexities, including the need for daily flights. Companies need to seek value-added services from third parties in their customer-centric approach.

Another challenge is linked to in-house production. Ready-to-use commercial radiopharmaceuticals are a recent innovation vs. in-house production, which remains common practice in some countries. While Sweden requires commercial production, Denmark justifies its continued use of in-house production by the need for a return on its investment in cyclotrons. While in-house production tends to be less expensive, ready-to-use products can address geographic challenges for patients who currently need to visit specific nuclear medicine centers.

Finally, another challenge for market access and pricing is a lack of transparency on HTA process existence and publication.

Best Practices in Market Access and Pricing

Companies with nuclear medicine products in development can take advantage of the best practices listed below for a successful market access and pricing strategy.

Market Access

1. Focus on value communication. Without an HTA, or with an HTA that is not made public, companies must demonstrate the value of their ready-to-use commercial product vs. the hospital’s own in-house, less expensive solution. A tailored value proposition helps to tap the competitive advantage of the commercial product over in-house production and other alternatives already on the market.
2. Collaborate with medical societies and patient associations to influence clinical guidelines towards the selection of the product, which in turn impacts hospital protocols, and is one of the main drivers for usage and purchase of radiopharmaceuticals.
3. Prepare an economic model that hospitals in countries with a well-established history of in-house production, such as Germany and Denmark, can update themselves to showcase the potential economic benefits of adopting the commercial product. This will help promote the shift from in-house labeling to ready-to-use radiopharmaceuticals.
4. Build a payer objection handler, a document which allows companies to anticipate and address possible objections that payers may raise during price and reimbursement negotiations or hospital purchasing decisions.
5. Prepare for tender management (i.e., timelines and terms of hospital purchasing agreements, tender structure, and award criteria).

Commercial

6. Understand the high variability in the profiles of nuclear medicine centers and professionals. Map these centers in detail across geographies, including their degree of specialization and capabilities in the nuclear medicine space, and capture new trends in the diagnostic space.
7. Create networking opportunities with nuclear medicine physicians (i.e., training) and expand target clinical stakeholders beyond them (i.e., radiochemists, oncologists, hospital managers).
8. Develop a commercial strategy on supply and discounts to offer to each customer (i.e., portfolio agreement, radioligands franchise from disease diagnosis to treatment).
9. Develop a robust internal demand plan, with a need for flexible prebooking of products, easy cancellation of purchase orders when needed, and a money-back guarantee approach in case patients don’t attend the scheduled visit. Imaging clinical decision-support, including software and training activities, are another upside.
10. Consider partnerships to protect the current market share and expand to other centers.

Geographic Differences

Capabilities, such as the existence of a hospital radiopharmacy unit, drive most of the varied performance in geographies. In some cases, companies can externalize the radiolabeling activities to commercial radiopharmacies that ship to third parties. This is common practice in Spain, for example.  In Lithuania, commercial products will contribute to soften the bottleneck on production. But hospitals with cyclotrons will continue using their in-house capacity for other purposes/therapeutic areas and will continue to benefit from their cyclotron investment.

However, regulatory frameworks across European markets increasingly mandate the adoption of commercial solutions once available, which should trigger the adoption of licensed options off the shelf. For instance, in Spain, the new regulation on radiopharmacies reveals that radiopharmacies should implement new standards on quality and safety, which implies an enormous investment in infrastructure that the National Health System could not afford. Hospitals with in-house production capacity face a similar situation on compliance with Good Manufacturing Practices.

In the EU4 countries (France, Germany, Italy, Spain), the UK, Sweden, and Norway, companies can also find commercial opportunities in the private market.

Finally, in some countries, Early Access Programs (EAPs) can benefit companies with innovative radiopharmaceuticals. For example, in France, an EAP enables a period of free pricing with full reimbursement. However, at the end of the EAP, a national reference price is negotiated and used to calculate paybacks and as a starting point for additional hospital discounts.

Conclusion

In Europe, the market access and pricing landscape for commercial radiopharmaceuticals aimed at diagnostic imaging presents both significant challenges and promising opportunities.

Evolving regulatory requirements, high production and distribution costs, limited reimbursement frameworks that hinder innovation, varying HTA frameworks, and the need for specialized infrastructure for distribution and administration underscore the complexity of navigating this market. These factors, together with lengthy pricing negotiations at the hospital level, influenced by the reliance on less expensive in-house production in some regions that need to pay-off their investment in infrastructure, creates significant pricing constraints for any innovative radiopharmaceuticals entering the market.

Despite these hurdles, the sector is fueled by the increasing demand for personalized medicine and innovations in molecular imaging. Key success factors include fostering collaboration between industry and healthcare providers, delivering tailored health economics data embedded in compelling value propositions that emphasize the advantages of ready-to-use commercial radiopharmaceuticals over in-house production, and providing value-added services. With these strategies in place, companies can demonstrate the impact of commercial solutions to facilitate adoption and achieve more favorable pricing and reimbursement outcomes.

How Can Alira Health Help?

Our team can provide insight into the complex market access issues surrounding radiopharmaceuticals. With a deep understanding of the challenges at national, regional, and hospital levels, we offer vital guidance to companies seeking to bring radiopharmaceutical products to the market. We can accompany you on each step of this complicated development journey.