Thinking Outside the Box: Sustainable Solutions to Drive Global Patient Access for Advanced Therapy Medicinal Products (ATMPs)
Butler E1, Whitehouse J1, Satherley A1, Furniss J1, Hurst S1, Paas M2, Casadei G3 , Gandjour A4, Miller P5, Owens G6
1 Lightning API, United Kingdom 2 AbbVie, United States; 3 University of Milan, Medical Biotechnology and Molecular Medicine, Italy; 4 Frankfurt School of Finance & Management, Germany; 5 Miller Economics, United Kingdom; 6 Gary Owens Associates, United States
Advanced Therapy Medicinal Products (ATMPs) include cell therapies, gene therapies, and tissue engineered products. Successful adoption of ATMPs, with potentially curative effects after one treatment cycle, can provide significant clinical and economic benefits to multiple stakeholders. However, limited data at launch, challenges quantifying long-term benefits and high upfront (or total) costs lead to clinical and economic uncertainty for payers. The complexity is highlighted by five European ATMP market withdrawals between 2014- 2019.
This research aims to explore the feasibility of new sustainable funding models to drive patient access for high cost, high value ATMPs from global and market specific perspectives. Methods An advisory meeting was held with EU and US HTA and budget holding stakeholders and senior industry executives. Participants reviewed existing ATMP financing and reimbursement approaches and explored the challenges with incentivising their development and commercialisation, whilst ensuring sustainable funding and management of payer uncertainty.
Feasible application of proposed payment* and financial** solutions from the advisory meeting were explored in further detail with a sample of n=18 payers in the US, France, Germany, Italy, Spain and the UK. Qualitative and quantitative methods were used to obtain market specific insights regarding the desirability and feasibility of various payment and financial models, in relation to both ATMPs with a short-to-mid-term duration of effect (1-5 years) and those with a long-term duration of effect (>10 years).
*(Payment models) annuity, pay-for-performance, conditional reimbursement, special funds for transformative treatments **(Financial models) re-insurance; risk-pooling; supplier credit; financial bonds
50% of payers believe that current models are adequate for the assessment of the clinical value of ATMPs and for achieving sustainable reimbursement.
Payers believe that challenges within HTA can occur due to the lack of mature efficacy data and limited patient numbers at the time of launch, not due to inherent limitations within the systems for the assessment of value. HTA representatives in the UK and France consider current assessment and funding models to be adequate for the evaluation and funding of ATMPs. Additionally, payers in Italy regard the AIFA innovation algorithm and potential for managed entry agreements with registry collection to be suitable for new ATMPs.
“The HTA process is adequate however, manufacturers do not listen to payers who tell them to wait until they have more mature data on effect. Rushing will have a detrimental effect on price.” Former Transparency Committee member, France
“The HTA process is adequate but the lack of evidence needs to be addressed… we may need evidence development solutions.” Former NICE committee member, UK
22% of payers believe that whilst the current assessment process is adequate for determining the clinical value of ATMPs, funding models need to adapt to achieve sustainable, value-based reimbursement.
In Germany, the introduction of risk-pooling from 2021 for covering a high proportion of costs for therapies costing >€100,000 per year is important to ensure the sustainability of reimbursement by sickness funds (however the negotiation of outcomes-based schemes with sickness funds and confidential rebates is expected to continue).
28% of payers do not believe that current assessment process and funding models are adequate to assess the clinical value of ATMPs and achieve sustainable reimbursement.
Spanish payers recognise the need for a system that incentivises the launch of new ATMPs in Spain, whilst minimising financial uncertainty associated with high-cost therapies with limited supporting data. US payers also favour models that ensure payment for long-term outcomes and risk sharing between healthcare plans.
“The HTA processes may need to be readjusted given the high uncertainty of launching ATMPs, pay for performance agreements and annuity payments need to be normalised.” Former advisor to the Ministry of Health, Spain
Figure 2. Payer preferences for managing the access and reimbursement for ATMPs with a short to mid-term duration of effect of 1-5 years (findings based on research with n=18 payers in the EU5 and US, September 2020)
In Europe, pay for performance and conditional reimbursement arrangements are the preferred access models for ATMPs with a short-to-mid-term duration of effect, to reduce uncertainty and financial risks for healthcare systems.
Recent initiatives in France (conditional ASMR) and Germany (conditional benefit level under the GSAV law) to enable an initial price to be set and reviewed based on ongoing registry data are considered important developments to support access to ATMPS and are likely to be followed by other European countries.
US payers consistently request a system that allows payment of ATMPs to be linked to clinical performance, whilst also enabling patients to be tracked between insurers (so that payments and risk can be distributed).
Figure 3. Payer preferences for managing the access and reimbursement for ATMPs with a long-term duration of effect of > 10 years (findings based on research with n=18 payers in the EU5 and US, September 2020)
For ATMPs with a long duration of effect (i.e. lifetime effect), payers have a higher interest in financial models to support sustainable access to potentially ‘curative’ therapies, whilst containing budget impact and ensuring investment is ‘well spent’. Potential models include financial bonds (where manufacturers receive upfront payment and healthcare systems pay a third party for pre-agreed clinical outcomes at the end of the bond), supplier credit arrangements and risk pooling (this will be implemented in Germany as of 2021 for therapies costing >€100,000 per year).
Across markets, payers recognise the increasing numbers of high cost ATMPs that are likely to launch over the next 5-10 years, and appreciate the potential role of financial models to enable timely patient access, whilst minimising financial exposure and ensuring manufacturers receive a return on their investment.
Importance of international collaboration and priority setting for ATMP development is recognised to address unmet clinical needs
Recommendations for inter-industry collaboration
An advisory meeting including European and US payers and industry executives was held in July 2020 to discuss sustainable access models for ATMPs. Meeting participants aligned on the need for interindustry collaboration to agree a common framework to address the challenges of developing ATMPs, whilst ensuring sustainable reimbursed access for patients. This should involve a consensus position on what is required for the sustainability of development (and avoiding market withdrawals for ATMPs as has previously occurred in Europe) and joint proposals on feasible funding models to support sustainable patient access whilst covering associated investment costs.
Recommendations for international priority setting
Payers and industry stakeholders recognise the value of international collaboration between clinical societies, governments and industry to develop a hierarchy of global unmet needs and clinical priorities for ATMP review.
For industry, this should reduce uncertainty (and therefore risk) regarding the value of investment in new therapies for specific indications. Collaboration will inform a common framework regarding acceptable levels of uncertainty for ATMPs at launch and models to reflect ongoing data generation in pricing and access decisions. This will also support industry to develop a variety of innovative market specific payment/financial models to facilitate sustainable, equitable access for patients. For payers/HTA bodies, this should provide the opportunity for early engagement with manufacturers developing high priority ATMPs, ensuring active involvement in supporting the pre- and post- launch evidence generation strategy
Conclusions and recommendations
Innovative payment and access agreements will be a key strategic requirement for ATMPs
Payers recognise the increasing numbers of high cost ATMPs that are likely to launch over the next 5-10 years, in many cases indicated for patient populations with high unmet needs, with limited supporting data at marketing authorisation. In addition, payers understand the potential future role of payment/ financial models to enable timely patient access, whilst minimising financial exposure for healthcare systems and ensuring manufacturers receive a return on their investment.
However, there is no single solution that will fit the requirements of all healthcare systems and the correct strategy will depend on the individual healthcare system, the indication in question and the available data at launch.
Companies should engage early with payers regarding proposed access models
Payers across most markets will be receptive to manufacturers that seek early engagement regarding new ATMPs (1-2 years pre-launch), and proactively propose access models that are “rational, practical, and feasible” for their healthcare system. The most favourable access models will balance the objectives for timely patient access to address unmet needs, whilst minimising uncertainty regarding the value-based payment for clinical outcomes.
Moving forwards, companies should seek to work with payers to implement access models within the existing infrastructure where possible (such as conditional reimbursement and pay for performance), and support with new initiatives if this is a ‘win-win’ for all parties (e.g. investing in patient registries/IT systems for long term RWE collection).
Inter-industry collaboration is recommended to address the challenges of ATMP review
There have been five withdrawals of ATMPs from the European market since 2014, principally due to lack of reimbursement and low uptake. Collaboration between manufacturers is recommended, to define a consensus position on what is required for a sustainable industry that incentivises development of ATMPs whilst ensuring equitable patient access. This consensus should build on expressed payer preferences for potential access models explored in this research, to support the development and implementation of sustainable funding models to drive patient access for high-cost, high-value ATMPs.
AMNOG: Act on the Reform of the Market for Medicinal Products; ASMR: Amélioration du Service Médical Rendu; GSAV: Gesetz für mehr Sicherheit in der Arzneimittelversorgung (Act for more safety in the supply of pharmaceuticals); HTA: Health Technology Assessment; IT: Information Technology; NICE: National Institute for Care and Excellence; RWE: Real World Evidence; TC: Transparency Committee
Article published 26 August 2021.