A review of the challenges and proposals for improving patient access to advanced therapeutic medicinal products in France

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.

France has begun granting access to ATMPs while maintaining existing processes of HAS

ATMPs that have launched in France recently have achieved ASMR levels (a determination of the medical benefit a product offers over current standard of care) that allow for central reimbursement via inclusion on the liste en sus. Maintaining national-level reimbursement for future ATMPs via the existing assessment processes pose the biggest barrier to sustainable patient access.

How a product is funded is dependent on the ASMR level granted by HAS – those with an ASMR of I–III are included on the liste en sus. Those with an ASMR IV or V can also be on the liste en sus if the relevant comparator is already listed on the liste en sus, however, products with an ASMR IV or V usually require funding through hospital budgets. Both reimbursement routes could pose challenges for ATMPs where costs are loaded upfront.

An ASMR level is granted based on a very structured assessment of evidence presented by the manufacturer. The challenge for ATMPs is similar to assessment challenges seen in other countries, meeting evidence requirements for positive reimbursement in a process not designed to assess ATMPs. Under the assessment criteria, achieving an ASMR I–III without survival data versus the standard of care treatment in France and with single-arm trial data is difficult. Yescarta and Luxturna did achieve this, highlighting the willingness in France to be flexible for innovative products. Even though there is a lack of long-term data, the efficacy level and unmet need motivated the Transparency Committee (TC) decision. Kymriah, on the other hand, only achieved an ASMR IV for one of its two indications. For a more sustainable and transparent approach, the assessment and awarding of ASMR levels for ATMPs should be evolved.

There seems to be recognition from HAS that the current assessment process can be challenging for ATMPs, which may provide an opportunity to explore solutions to address these challenges

These could include guidance on acceptance of data from single arm trials, indirect treatment comparisons (ITC), surrogate endpoints and real-world evidence (RWE), which would provide ATMP manufacturers with greater certainty.

Historically, payers in France have been reluctant to engage in more complex managed-entry agreements (MEAs), such as outcomes-based schemes, which could help in managing evidential and financial uncertainty. However, recent negotiations of CAR-T have included such arrangements. Additional proposals to manage affordability challenges include linking RWE data collection with outcomes-based rebates and the removal of barriers to annuity payments to address skewed upfront costs.

Despite reimbursement and assessment barriers, patients in France can currently gain access to ATMPs in cross-border specialist treatment centres in certain circumstances. The sustainability of this type of availability is uncertain as there is no standard approach for ensuring access for future ATMPs. Given the importance of the French market and the high priority put on treating rare diseases, it is relatively unlikely that this scenario will play out regularly. However, a policy on providing patient access to treatment centres in cross-border scenarios would provide clarity to patients and treating physicians on the protocols for ensuring patients can get access when a treatment is not available in a specialist centre in France.

Early dialogue with the Ministry of Health (MoH) could further identify the resource needs for ATMPs in advance so that patient access is not delayed at the time of launch. With regard to certification of treatment centres, a requirement for CAR-T delivery, France is well prepared and aiming to have 15-20 certified centres by the end of 2019. Leveraging this experience will be important for preparing for delivery of future ATMPs.

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