In this article, originally published in European Pharmaceutical Manufacturer, CRA’s Cécile Matthews, Ioanna Stefani and Paula Urruticoechea assess the changes to the Autorisation Temporaire d’Utilisation (ATU) programme and what it means for patients with diseases where there is an unmet need in therapies.
The French healthcare system is expected to undergo a major transformation in July this year with the reform of the popular but complex and cumbersome Autorisation Temporaire d’Utilisation (ATU) programme. While initially aimed at simplifying the process, the reform seems to indicate a desire to control spending on the overly-subscribed ATU program, potentially at the cost of patient access to innovation. So as decision-making shifts from the regulatory agency (Agence nationale de sécurité du médicament et des produits de santé, ANSM) to the HTA body (Haute Autorité de Santé, HAS), we assess the future implications for industry.
What is the current situation?
The temporary authorisation programme in France is intended to provide early access to medicines for patients with a severe or rare disease with high unmet need (i.e. with no authorised therapeutic alternatives available). As a result of expanded use of ATUs over recent years, funding of new products through the system has grown to over €1 billion a year.
Access to pre-authorised medications in France may be granted through the nominative ATU (nATU) or cohort ATU (cATU). The nATU is issued for a single, named patient, at the request of the prescribing physician. However, the more frequently used cATU is issued at the request of the manufacturer to a group of patients treated and monitored according to a well-defined protocol. There are always requirements for follow-up and data collection and manufacturers must commit to submit a market authorisation application within a pre-determined period.
The cATU programme offers several benefits to manufacturers. Firstly, there is the option to set a price freely, which helps establish a price benchmark ahead of formal price negotiations. In addition, the cATU supports the claim of high unmet need, often leading to a higher rate on the improvement of medical benefit (Amélioration du Service Médical Rendu, ASMR) which is beneficial for price negotiations. Furthermore, the manufacturer can leverage aggregated real-world evidence (RWE) data from French patients to include in the submission dossier and support the health technology assessment (HTA).
What has changed for the ATU?
The most recent French Social Security law of 14th December 2020 (Article 78- loi de financement de la sécurité sociale, FSSL) for the healthcare plan of 2021, set out the changes. The ATU programme, previously divided into six systems, has now been grouped into two: an early access authorisation programme (Autorisation d’accès précoce, AAP) which includes the cATU and a compassionate access programme (Autorisation d’accès compassionnel, AAC) which includes nATU, among others. The reforms have come into force no later than 1st July 2021.
What is new about the EAP?
Manufacturers will now be required to make all AAP requests to HAS not to the ANSM. While the ANSM will still be consulted, the decision-making power will lie with HAS, giving it access to clinical evidence prior to European Medicines Agency (EMA) approval and dossier submission. As the AAP data will need to be collected using a standardised approach, it is possible that HAS will consider these data in the clinical assessment by the transparency committee (Commission de la Transparence, TC).
Another novel aspect of the reforms is the introduction of the presumption of innovation for the products, compared with the most clinically relevant comparator. It is currently unclear how HAS will define and quantify innovation, but there is a risk that this may negatively impact the number of products eligible for the AAP programme, particularly for products with immature data. It is also unclear whether HAS will continue to consider unmet need as part of the decision. For example, 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?
What is new about the CAP?
Like the AAP requirements, the AAC criteria are now stricter as the manufacturer needs to demonstrate that the efficacy and safety of a product is “strongly presumed,” as opposed to “considered’’ to be favourable under the old system. The manufacturer must not only follow a well-established clinical protocol and collect data during the period required by HAS, but also needs to demonstrate that trials have started. While the price of AACs will remain confidential, it will now be set by the authorities and not by the manufacturer.
What does this mean for pharma?
While it remains to be seen how the AAP and AAC systems will impact pricing and market access in the future, the French authorities seem to have increased the hurdles to early access. Depending on the interpretation HAS gives to its definition of 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 comparator.
The downstream effects may go beyond fewer AAP approvals compared with the ATU system and may impact HTA assessments. While having the HAS conduct both assessments may be an opportunity to bring more coherence between early access and HTA evaluations, it may also increase time to reimbursement, by adding workload to an already burdened HAS.
Under the reforms, fewer products are likely to be approved compared with the previous ATU system. For many years, France has claimed its early access programme is the most generous and fairest for patients in Europe. Will this still be the case in the future?