Pharmaceutical HTA for ATMPs: Pricing and Reimbursement

The value proposition for one-off, potentially curative Advanced Therapy Medicinal Products (ATMPs) is fundamentally different from that of chronic treatments with traditional medicines.

The substantial single upfront payment often associated with these treatments can lead to adverse payment decisions despite the potential for significant long-term benefits and savings beyond the healthcare system. Recognising this, the European Commission (EC) and the United Kingdom (UK) are responding to pressures from industry and patient groups to evolve the funding model for ATMPs, resulting in a changing landscape for health technology assessment (HTA) of these medicinal products.

A comprehensive understanding of current legislative and lobbying activities, alongside recent approval and reimbursement precedents, can support informed decision-making and foster high-quality interactions between clients and regulators/HTA bodies. This knowledge enhances the value of our advice to clients, offering persuasive arguments for drug developers that:

• • HTA should be addressed promptly as a developmental issue, similar to Paediatric Investigation Plans (PIPs).
  • Reimbursement can be achievable, even in the face of challenges such as small patient numbers or high costs. The precedent set by products like CAR-Ts shows that securing reimbursement is possible despite these obstacles. Therefore, not achieving reimbursement should not be viewed as inevitable; instead, it highlights a potential strategic failure if regulatory approval is followed by withdrawal.

This approach also reinforces the recommendation to engage HTA partners at the appropriate stage of development. Combined with our in-house medical technology capabilities and experience with initiatives like PRIME and the Innovation Task Force (ITF), it promotes crucial integrated thinking for ATMP clients.

Current Landscape

Innovative and promising therapies do not always reach patients. Companies may decide not to market products in one or more countries. Numerous factors, such as national pricing and reimbursement policies, the size of the population, the organisation of health systems, and national administrative procedures, could influence this decision, resulting in smaller and less wealthy markets facing these problems.

Patients in the European Union (EU) still have diverse levels of access to medicines. Market access of ATMPs is key to making innovative and potentially therapies available for patients.

ATMPs are challenging concepts, both in terms of science and manufacturing. The ATMPs are often administered in a few highly specialised centres due to the need for care around the patients when the medicines have been administered (need for new equipment, need for intensive-care unit bed facilities) or even due to the stability of the medicinal product, which adds to the cost of the ATMPs and related healthcare system. As a result, the biggest challenge for many ATMPs is the price tag associated with the therapy.

Overview of European Commission’s Health Assessment Regulation

Each European country has its own HTA bodies with varying priorities and methods, significantly influencing assessment outcomes. In some countries, such as Italy and Spain, multiple or regional HTA bodies operate, adding to the complexity.

None of the HTA bodies have specialised ATMP committees. This general lack of established mechanisms to capture the specific benefits of ATMPs can delay patient access to these therapies. Most approved ATMPs have undergone HTA evaluations. However, due to the limited number of products, clear general reimbursement strategies for ATMPs in Europe have yet to emerge. There is an ongoing debate about the suitability of current HTA methods for ATMP appraisal.

Innovative Payment Models and Associated Challenges for ATMPs

Unique Challenges in Clinical Assessment and Reimbursement of One-Time ATMP Treatments

The administration of ATMPs often involves one-time treatments, unlike most medicines, which can be discontinued if no response is observed. This one-time nature poses unique challenges for both clinical assessment and reimbursement decisions. For example, out of 15 indications (13 ATMPs) in a sampled study, 14 were intended for single administration. Due to the limited and often preliminary evidence available at the time of launch, the data presented for HTA and reimbursement may be insufficient for healthcare systems to accurately assess their added therapeutic value (Angelis et al., 2020; Lloyd-Williams and Hughes, 2021).

The European Commission (EC) adopted the Regulation on Health Technology Assessment (EU HTA Regulation; No. 2021/2282) with the primary objectives being to strengthen the quality of HTAs across the EU to ensure efficient use of resources, to avoid duplication of industry and national HTA body efforts; and to ensure the long-term sustainability of EU HTA cooperation. The EU HTA Regulation formally entered into force on 11 January 2022. It will apply to Oncologic & Advanced Therapy Medicinal Products (ATMPs) after a three-year implementation period (i.e., 12 January 2025) in the first instance, followed by Orphan Medicinal Products (OMPs) in 2028, and all other Centrally Approved Medicines from 2030 onward.

Introduction of EU-Level Joint Clinical Assessments (JCA) in the EU HTA Regulation

One of the most essential elements of the EU HTA Regulation is the introduction of EU-level Joint Clinical Assessments (JCA). These joint assessments by experts from national HTA bodies at the EU level are the scientific compilation and description of a comparative analysis of the available clinical evidence of a health technology (e.g., a medicine) compared to one or more health technologies or procedures. In effect, they are relative clinical and safety effectiveness assessments. The parameters under the JCA scope will include the patient population, the intervention, relevant comparators, and health outcomes (PICO).

JCA are envisaged to generate high-quality scientific reports supporting Member States in making more evidence-based and timely decisions on patient access to new medicines. Pricing and reimbursement will, however, remain the responsibility of the individual Member State (MS).

Strategy Considerations

The regulation’s application date is rapidly approaching, and it is crucial to the success of the EU HTA procedure to get this right from the beginning. As a manufacturer or the Marketing Authorisation Holders (MAH) for ATMPs, you need to think about de-risking strategies from the regulatory perspective and from meeting the expectations of reimbursement bodies.

Many ATMP trials are open-label, non-randomised, single-arm studies without control or using historical controls. From a regulatory perspective, there is no real valid active comparator, but HTA bodies are looking for comparators, so you need to agree on valid historical controls and endpoints that would be more relevant for HTA bodies.

While there can be many good reasons why randomised controlled trials are not feasible for some drugs, the lack of randomisation can add to the uncertainty. For HTA bodies, uncertainty about long-term effects is a big issue. This needs to be characterised and factored in your de-risking strategy and discussion with HTA bodies.

Implementing the HTA Regulation means a change in mindset, ways of working, and methodology.

While innovative payment models like conditional reimbursement, pay-for-performance, and annuity-based payments hold promise for managing the high costs and uncertainties associated with ATMPs, their implementation is fraught with challenges. Addressing these challenges requires collaboration between healthcare providers, payers, regulators, and manufacturers and investments in data infrastructure and standardisation. By overcoming these hurdles, healthcare systems can better accommodate the unique needs of ATMPs, ensuring timely access for patients while maintaining financial sustainability.

DLRC by Your Side, Helping You Navigate the Challenges Ahead

The regulatory system capacity of JSC has been one of the most significant issues in the industry to date. Current JSC availability has been very low, and future availability through the Coordinating Group is currently unknown.

Engaging with regulators and HTA bodies early on is critical in the evolving landscape. DLRC experts can help you achieve the desired regulatory outcome and market access strategy.

Summary

The market access of ATMPs remains a significant challenge across Europe due to diverse national pricing and reimbursement policies, varying health system structures, and administrative procedures. This inconsistency particularly affects smaller and less wealthy markets, resulting in uneven patient access to innovative therapies. The high costs and complexity of ATMPs, often requiring specialised administration centres, further complicate their integration into healthcare systems. Addressing these challenges is essential for making life-saving treatments available to all patients in the EU.

Innovative payment models such as conditional reimbursement, pay-for-performance, and annuity-based payments are being explored to overcome these barriers. The implementation of the EU HTA Regulation, introducing Joint Clinical Assessments (JCA), aims to streamline evaluations and promote equitable access across member states. However, successful integration requires collaboration among healthcare providers, payers, regulators, and manufacturers, along with investments in data infrastructure and standardisation. Engaging early with regulators and HTA bodies, developing de-risking strategies, and adapting to the evolving HTA landscape are crucial steps for ensuring timely patient access to ATMPs while maintaining financial sustainability.

The takeaway from this post is that it is complex. There is a lot to do between now and January 2025, but we cannot wait until then. Do not delay; contact DLRC’s experts at hello@dlrcgroup.com or use the links below.