On 1 July 2021, France made changes to its long-standing Authorization for Temporary Use (ATU) and Recommendation for Temporary Use (RTU) systems. The reforms seek to simplify existing rules, make early access and off-label use more predictable for all users, and ensure the sustainability of these programs for the public health insurance system 1. Although the new ATU programme may support more efficient use of healthcare spending, could it mean fewer patients receive early access to treatments in France and what does this mean for manufacturers which plan to enter the French market?
What has changed for ATU?
ATU was implemented in 1994 with the aim of providing early drug access to patients with a severe or rare disease with high unmet need and for which no authorised alternatives were available. This scheme was the key route for manufactures to minimise access delays and bring life changing-treatments for patients as early as possible, resulting in early access to treatments such as targeted therapies, immunotherapy and cell and gene therapies.
The ATU programme was divided into six sub-systems, but under the reforms these have been combined into just two new mechanisms: Early access programme (EAP) which incorporates the previous cATU programme (access issued to a group of patients treated and monitored according to a well-defined protocol) and Compassionate access programme which incorporates the former nATU (access issued to a single named patient) and RTU programme (recommendation for off-label use).
Early access programme (EAP)
The new EAP system will be used primarily for innovative medicines and requests for this route will have to be made to HAS (the High Authority for Health – Haute Autorité de Santé). Previously the ANSM (the French Medicines Agency – Agence nationale de sécurité du médicament et des produits de santé) was responsible for the ATU and RTU, with subsequent reimbursement decision, and it was not bound to take a decision on ATU applications within a set period. HAS now has three months from the notification that the EAP application is complete to communicate its decision and the manufacturer must also agree to make the product available within two months following the grant of the EAP2. All of this could potentially minimize early access delays.
Furthermore, the overall timelines to reimbursement may be shortened. As HAS is now a main decision maker for early access, it will have access to clinical evidence prior to European Medicines Agency (EMA) approval and reimbursement dossier submission. As the EAP data will need to be collected using a standardised approach, it is possible that HAS will consider these data in the clinical assessment. If so, this could lead to faster HTA review by the CT (Transparency Committee – Commission de la Transparence) and quicker time to reimbursement 2.
Another novel aspect of the reforms is the introduction of the presumption of innovation for the products, compared with the most clinically relevant comparator 3. Although it is currently unclear how HAS will define and quantify innovation, there is a risk that this may negatively impact the number of products eligible for the EAP programme, particularly for products with more immature data. In addition, it is unclear whether HAS will continue to consider unmet need as part of the decision i.e. does a small magnitude of improvement in an otherwise untreated population with poor outcomes warrant early access, or will it be reserved for those products showing ‘significant’ benefit, regardless of unmet need? As the CT considers the level of unmet need during the clinical evaluation, it is possible that this will continue to be taken into account for early access programmes.
The manufacturer is still able to set a free price for these products and if the final negotiated price is lower than the price set during the EAP programme, manufacturers will be required to pay back the difference. However, the mechanism for payback has changed and under the new reforms, on top of the mentioned rebate, there is an annual rebate which depends on the annual sales under EAP1.
Compassionate access programme (CAP)
The CAP scheme is for medicines which are not necessarily innovative and which are not intended to be commercialised in the indication in question, but which meet a therapeutic need. The new eligibility criteria for this route is the condition of the absence of commercial clinical research i.e. there is no clinical research underway for commercial purposes. Furthermore, to be eligible for the new CAP scheme, the manufacturer now needs to demonstrate that the efficacy and safety of a given product is ‘”strongly presumed,’’ as opposed to ‘’considered’’ to be favourable which was the case under the old system 2,3. The manufacturer must follow a well-established clinical protocol and collect data during the period required by HAS. A limit on the total number of CAP requests for compassionate access authorization (AACs – former nATUs) per product has been introduced and, if reached, the manufacturer has the option to apply for an EAP. Given the introduction of the new limit on AACs, this reform could lead to a lower number of patients able to benefit from a CAP. The pricing and reimbursement of the product under CAP will depend whether or not the product is reimbursed in another indication. If it is, the price and reimbursement of the product in reimbursed indication will apply to the indication covered by CAP. If the product is not reimbursed in another indication, the company is free to set the price for their product under CAP 1.
Although the new ATU scheme aims to simplify the mechanisms for early access, and to ensure faster access to new medicines for patients without other treatment options, it seems that the hurdles for early access have increased. Depending on how HAS interprets innovation, the bar for evidence requirements will now be higher, both in terms of the quality and quantity of evidence needed to demonstrate innovation and how innovation can be articulated in the absence of a comparator4. Furthermore, as HAS now conducts both early access and HTA assessments, it may mean more coherence between the two processes, but it may also increase time to reimbursement, by adding workload to an already burdened HAS.
Therefore, it is possible that under the reforms, fewer EAP products will be approved compared with the previous cATU system and subsequently fewer patients would have access to potentially much-needed treatments. For many years, France has claimed its early access programme is the most generous and fairest for patients in Europe4. It remains to be seen if this will still be the case in the future.
- Léna Beley, Bart Van Vooren & Peter Bogaert. New Early Access and Off-Label Use Rules in France. July 6, 2021 https://www.insideeulifesciences.com/2021/07/06/new-early-access-and-off-label-use-rules-in-france/
- Cécile Matthews, Ioanna Stefani, Paula Urruticoechea. France’s temporary authorisation (ATU) programme: reform implications. June 21, 2021 https://www.europeanpharmaceuticalreview.com/article/156994/frances-temporary-authorisation-atu-programme-reform-implications/
- France’s ATU Scheme Reform to Come into Force from July. June 28, 2021 https://www.eversana.com/2021/06/28/frances-atu-scheme-reform-to-come-into-force-from-july/
- Paula Urruticoechea, Cecile Matthews, Ioanna Stefani. What reforms in the French ATU systems means for patients and pharma. July 13, 2021 https://pharmaceuticalmanufacturer.media/pharma-manufacturing-news/new-drug-development-approvals-regulatory-news/reforms-in-the-french-atu-system-increased-payer-recognition/