info@rareimpact.euA review of the challenges and proposals for improving patient access to advanced therapeutic medicinal products in Italy
Executive Summary
RARE IMPACT is a multi-stakeholder initiative working to improve patient access to advanced therapy medicinal products (ATMPs). This patient-focused initiative aims to assess challenges and propose actionable solutions to concerns regarding access to these transformative rare disease treatments in Europe. Through engagement with health technology assessment (HTA) agencies, regulatory bodies, payers, patient groups, clinicians, manufacturers and other experts across Europe, RARE IMPACT partners identified challenges and have proposed solutions for better access to ATMPs in Europe.
This report aims to stimulate multi-level stakeholder discussions on patient access to ATMPs and is not intended to capture all challenges to patient access to ATMPs. The RARE IMPACT initiative was launched at the European Conference on Rare Diseases and Orphan Products in 2018.
Overall, Italy is well-advanced in assuring and managing reimbursement and patient access to ATMPs for rare diseases
Three out of the first four ATMPs to receive Marketing Authorisation were developed in Italy and Italy has been progressive in engaging with manufacturers to develop outcomes-based agreements for ATMPs. Yet because of the innovative nature of these therapies, Italy, like all other countries, still faces challenges to ensuring patient access.
The main challenge to patient access to ATMPs for rare diseases in Italy relates to assessment of the added value of the technology versus other existing therapies at the national and regional levels. The added value, integrated with the severity of the target pathology and the data quality of the clinical study, drives the assessment of the innovative status. Reaching such status facilitates access in terms of price levels, special funding and time to market at the national and, importantly, regional level.
Attaining this status relies on data requirements that can be difficult for ATMPs to fulfil, since manufacturers face inherent limitations in producing conventional evidence for such products. If innovative status is not granted, the national (AIFA) and regional health authorities are less likely to accept such a novel therapy based on strong clinical needs and will rather focus on economic elements, such as cost offsets. This may cause delays in the process and create a risk of regional inequalities in patient access. A potential solution would be national level assessment and funding via either a national level ATMP exemption conditional on evidence collection and specified criteria enabling early access pre-negotiations (similarly to Law 648), or a national level outcomes-based agreement.
Affordability represents a potential barrier to patient access to ATMPs (and other innovative therapies) in Italy. While outcomes-based agreements have been scrutinised, they are in place for ATMPs. Maintaining these types of agreements is of particular importance for ATMPs in order to link the clinical benefit of these products with reimbursement. This is also important for the sustainability of the pharmaceutical budget and innovative funds. As more ATMPs become available, the proportion of the innovative funds that will be attributed to ATMPs will also rise. Without outcomes-based and annuity agreements there is a risk that the fund may not be large enough to cover all ATMPs, as it is also largely used by existing products. To date, the two approved CAR-T therapies have become reimbursed using an innovative ‘payment at result’ model, conditioned on the results. Thus, the national initiative (via the ATMP exemption or the outcomes-based agreement) should be linked to the innovative fund conditional evidence gathering by using registries at supranational level (i.e., European Reference Networks).
Budget impact plays an important role within pricing and reimbursement (P&R) assessments, but it does not typically capture long-term cost offsets and thus may not fully reflect the long-term cost profile. Recent focus on price transparency could require manufacturers to provide details on research and development costs to justify pricing. Payers and policymakers at both the Italian and European level need to be educated on the specificities of ATMPs, such as the therapeutic profile (especially for one-off ATMPs), the complexity of manufacturing and how the business model differs to that of traditional pharmaceuticals.
The availability of ATMPs for patients has been good in Italy. Patients can and have received access to treatment via cross-border initiatives (e.g., E112), and Italy is a leader in providing pathways for cross-border treatment when a single treatment centre is used. A recent example is Strimvelis, a gene therapy for the very rare disease severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID), where patients travel from across Europe to be treated in Milan. The sustainability of using cross-border initiatives to achieve patient access in Italy is uncertain. ADA-SCID is an ultra-orphan disease and the number of patients eligible for Strimvelis across Europe is extremely low. With more ATMPs becoming available and ATMPs for diseases with higher patient numbers, the scalability of these programmes requires continued effort.
Some solutions to these challenges are already being implemented in Italy, and others are feasible with minimal interruption to current patient access procedures
More innovative funding models and schemes, as well as better acceptance of the unconventional evidence produced by ATMPs, are all possible solutions that could alleviate some of the existing challenges.
|
Domain (Impact)* |
Challenge |
Proposed Solution |
Feasibility** |
|---|---|---|---|
| Assessment | |||
| 4 | It may be difficult to produce evidence for ATMPs that satisfy requirements for achieving innovative status | Adjustment in the procedure for including ATMPs in the innovative fund and dialogue with AIFA and Scientific Institutions on data collection | ++ |
| 4 | If innovative status is not achieved, regional HTA and formulary committees represent an additional hurdle and delay for ATMPs | Centralise the assessment at the national level and avoid variation in reimbursement criteria at the regional level | ++ |
| 4 | At both the national and regional level, issues of evidence quality will represent a significant challenge | Early dialogue regarding post-market access data collection to inform outcomes-based agreements | ++ |
| Affordability | |||
| 4 | Italy has created two special budgets (€500m each, so far) to fund innovative drugs for 3 years after their launch (oncology and non-oncology drugs) | The €500m for each budget need to be confirmed in the Financial Law. It needs to be supported by a forecast of the resources needed by the expected new innovative drugs and the resources that will not be absorbed by existing innovative drugs after 3 years from their launch. Innovative funding options could be explored to decrease the annual impact on the specialist fund | ++ |
| 4 | Budget impact does not capture long-term cost offsets and typically looks at the healthcare budget in isolation | There is a potential recognition of the value of ATMPs and innovative models can be proposed during negotiations to optimise budget impact | + |
| 4 | Recent legislation calls for transparency in price setting and the inclusion of R&D costs in the absence of a comparator | Educate policymakers on differences between the business model of ATMPs and traditional pharmaceuticals to highlight the need for specific policies for ATMPs | ++ |
| Availability | |||
| 0 | Availability is not likely to be a major issue – patients can and have received access to treatment via cross-border initiatives | Italy has led the way in cross-border single treatment centre healthcare provision, for example, with Strimvelis | + |
| Accessibility | |||
| 2 | There can be a delay in patient access at the regional level due to the absence of a DRG and criteria for reimbursement | Early dialogue between manufacturers, AIFA and regions where treatment centres are located, to prepare for access at the time of the reimbursement decision | + |
| 2 | The capacity and expertise of local centres to deliver products and services is variable between regions | Identification of specialist treatment centres, and full utilisation of ERNs, is required to ensure concentration of expertise | +++ |
| 2 | Establishing registries for a new product can be a hurdle and can delay patient uptake; not all registries are aligned at the European level | Early communication with AIFA to establish requirements for registries. This can be conducted prior to Marketing Authorisation. Alignment of registry and real-world evidence requirements at the European level (e.g., EMA, ERNs) | + |
Notes
*The working group assessment of the relative impact of the challenge of each domain on patient access is represented by Harvey balls from highest (represented by a full blue Harvey ball) to lowest (represented by an empty, white Harvey ball); **Feasibility: Working Group assessment of feasibility of solutions to be implemented. + low feasibility, ++ medium feasibility, +++ high feasibility.
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