Article
Early Access Program in France: How much of an opportunity is it?
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Henri Leleu, MD, PhD
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Martin Blachier, MD, MPH
France’s Early Access Program (EAP) promises faster patient access to groundbreaking treatments—but is it truly an opportunity or a bureaucratic maze? With stricter regulations, evolving data requirements, and industry concerns regarding the burden of the mandatory associated real-world data collection, the future of early access hangs in the balance. Here’s what you need to know about the shifting landscape of EAP in France. This is the first article in a three-part series in which we explore the current structure of France’s EAP, examine how it may evolve in the coming years, and assess the changes in real-world data collection within the Accès Précoce (AP, Early Access) framework.
France has a long tradition of the Early Access Program (EAP)
Timely access to innovative and effective treatments is a cornerstone of modern healthcare. However, patients often face significant delays, sometimes extending to months or even years, between a medicine's marketing authorisation and its actual availability. These delays are frequently caused by sequential, siloed assessments conducted by regulatory authorities and health technology assessment (HTA) bodies.
According to the 2024 EFPIA Patient W.A.I.T. Indicator, the median time to patient access for new medicines in France is 549 days. For individuals with serious, often life-threatening conditions with no existing therapeutic alternatives, such prolonged wait times can drastically reduce their chances of survival.
According to the 2024 EFPIA Patient W.A.I.T. Indicator, the median time to patient access for new medicines in France is 549 days. For individuals with serious, often life-threatening conditions with no existing therapeutic alternatives, such prolonged wait times can drastically reduce their chances of survival.
EAPs offer significantly faster access to innovative, life-saving treatments, typically in under 100 days. In France, the standard pathway for a new medicine involves two key steps: first, obtaining marketing authorisation from the European Medicines Agency (EMA) or the French National Agency for Medicines and Health Products Safety (ANSM); and second, securing pricing and reimbursement approval from the French National Authority for Health (HAS). EAPs can be granted before a medicine has received marketing authorisation or before pricing and reimbursement decisions have been finalised. Thus, EAPs can carry significant regulatory and financial risks. If subsequent evaluations by HAS or ANSM fail to confirm the anticipated clinical benefit, companies may be required to reimburse the cost of treatments prescribed during the EAP period. This risk is especially pronounced if the freely set price during the EAP is later deemed too high relative to the value assessed by HAS. For ANSM and HAS, it is essential to avoid situations where early access is granted to products that may later prove ineffective or unsafe, or where temporary access transforms into coverage for drugs that ultimately fail to demonstrate value.
France’s EAP is often recognised as one of the most ambitious in Europe for enabling rapid patient access to innovation. In 2021, the program underwent a major reform, replacing the long-standing Autorisation Temporaire d’Utilisation (ATU) scheme, which had been in place since 1994, with the current Accès Précoce (AP, Early Access) framework. While preserving the founding principles of the ATU, widely praised by patient, physician, and industry representatives as “extraordinary,” “particularly well-organised and efficient,” “an essential mechanism,” “an incredible opportunity for access to treatment,” the reform sought to strengthen governance, streamline procedures, and address some of the structural limitations of the earlier system, particularly around real-world data collection, transparency, and financing.
In this in-depth series, we will explore the current structure of France’s EAP, examine how it may evolve in the coming years, and assess the potential role of the National Healthcare Data System (SNDS) in supporting real-world data collection within the AP framework.
France’s EAP is often recognised as one of the most ambitious in Europe for enabling rapid patient access to innovation. In 2021, the program underwent a major reform, replacing the long-standing Autorisation Temporaire d’Utilisation (ATU) scheme, which had been in place since 1994, with the current Accès Précoce (AP, Early Access) framework. While preserving the founding principles of the ATU, widely praised by patient, physician, and industry representatives as “extraordinary,” “particularly well-organised and efficient,” “an essential mechanism,” “an incredible opportunity for access to treatment,” the reform sought to strengthen governance, streamline procedures, and address some of the structural limitations of the earlier system, particularly around real-world data collection, transparency, and financing.
In this in-depth series, we will explore the current structure of France’s EAP, examine how it may evolve in the coming years, and assess the potential role of the National Healthcare Data System (SNDS) in supporting real-world data collection within the AP framework.
A Two-Tiered System: Pre-Marketing Authorisation (AMM) and Post-AMM
The current AP framework in France is organised into a two-tier system:
In both AP1 and AP2 cases, the early access decision is made by HAS. For AP1, this follows a binding opinion from ANSM, which assesses the drug’s presumed efficacy and safety. Once an application (AP1 or AP2) is submitted, the evaluation that has to be legally completed within 90 days by HAS includes:
As part of its review process, HAS may invite patient associations, external experts, and manufacturers to present or defend their applications in dedicated hearings.
- Pre-AMM Access (AP1): This pathway is for innovative drugs that have not yet received AMM. Approval under AP1 requires robust preliminary data supporting efficacy and safety, as well as a formal commitment from the manufacturer to submit an AMM application. Access under AP1 ends once the AMM is granted.
- Post-AMM Access (AP2): This applies to drugs that already have AMM but are not yet reimbursed by the National Health Insurance (NHI) system. AP2 can be requested either as a continuation of AP1 or as a standalone (de novo) application. To ensure uninterrupted access for patients who began treatment under AP1, manufacturers must file for reimbursement within one month of receiving AMM.
In both AP1 and AP2 cases, the early access decision is made by HAS. For AP1, this follows a binding opinion from ANSM, which assesses the drug’s presumed efficacy and safety. Once an application (AP1 or AP2) is submitted, the evaluation that has to be legally completed within 90 days by HAS includes:
- An initial scientific opinion from ANSM (for AP1 only);
- A review of the eligibility criteria;
- An assessment of the clinical development plan, including trial design and maturity;
- An evaluation of the real-world data strategy, which must be outlined in a Protocole d’Utilisation Temporaire et Recueil de Données (PUT-RD) (or Temporary Use and Data Collection Protocol).
As part of its review process, HAS may invite patient associations, external experts, and manufacturers to present or defend their applications in dedicated hearings.
HAS requires that four major conditions are met to qualify for EAP
For a drug to qualify for AP, HAS requires that four major conditions be met within the scope of the requested access, which may be narrower than the eventual AMM. Within this defined scope:
- The treatment must address a serious, rare, or disabling disease. This includes conditions characterized by clinical severity, such as high mortality or morbidity, by chronic or irreversible progression, including slowly evolving diseases that are not immediately life-threatening, or by rarity, defined as a prevalence below 5 per 10,000 individuals.
- There must be no appropriate therapeutic alternative within the requested indication. To fulfill this condition, no available treatment should:
- Hold an AMM in the same indication or, on a case-by-case basis, be used off-label in accordance with French or international guidelines supported by adequate safety and efficacy data;
- And be accessible and available across France without current or foreseeable shortages;
- And be reimbursed or funded through NHI;
- And present superior clinical data compared to the treatment under AP request. If existing treatments demonstrate equivalence or non-inferiority, the new treatment may still qualify if it brings added value by simplifying the care pathway, improving safety, enhancing quality of life (e.g. transitioning from injectable to oral form), improving the treatment's intent (e.g. from palliative to curative), or offering a new delivery form suited to a specific population (e.g. pediatric formulation).
- The treatment cannot be postponed, meaning that any delay would carry significant clinical risk, potentially lead to irreversible harm, or result in missing a critical therapeutic window
- The drug must be presumed innovative. Innovation, as defined by HAS, includes meaningful improvements in patient care, such as efficacy, safety, quality of life, or health system organisation. For AP1, the request must be backed by either promising clinical data (intermediate or final results) or, if filed significantly ahead of the projected AMM date, conclusive preliminary findings; for AP2, the request must show conclusive efficacy results based on the primary endpoint submitted for AMM. The treatment must be supported by a rigorous clinical development plan including clinical trials with appropriate methodology. Methodologies considered inappropriate include phase I trials, non-inferiority trials, non-comparative trials lacking strong rationale, trials using irrelevant comparators, and studies with ill-suited primary endpoints.
Some treatments that did not qualify for in 2024 illustrate the strict eligibility criteria applied by French health authorities. These include efanesoctocog alfa for prophylaxis in severe hemophilia A, isatuximab in combination with bortezomib, lenalidomide, and dexamethasone for previously untreated multiple myeloma or pembrolizumab in combination with gemcitabine and cisplatin for first-line treatment of adults with locally advanced unresectable or metastatic biliary tract carcinoma which were declined due to the availability of existing treatment options and the possibility of delaying therapy. They also include benralizumab for eosinophilic granulomatosis not responding to mepolizumab, which was rejected as ANSM concluded that sufficient efficacy data were lacking; or lomitapide, as an adjunct to a low-fat diet and other lipid-lowering therapies in uncontrolled homozygous familial hypercholesterolemia, which was denied due to a lack of presumed innovation
Any EAP approval is contingent on the sponsor implementing a PUT-RD
The purpose of the PUT-RD is to gather real-world evidence on how the treatment is used in clinical practice. While these data do not replace clinical trials, they are considered complementary, providing valuable insights into effectiveness, safety, and care delivery in real-life settings. For AP1 (pre-AMM access), the expected data set includes patient characteristics and prescriber context, treatment utilization data (such as dosage, regimen, and adherence), measures of effectiveness, including patient-reported outcomes (PROs), and safety information. These data may support decisions on AP renewal, inform HTAs for pricing and reimbursement, and help validate the treatment’s real-world benefit. For AP2 (post-AMM access), expectations are lower; data collection typically focuses on patient demographics, prescriber settings, and usage patterns, in addition to the standard post-authorisation safety data collected via the routine pharmacovigilance system.
HAS encourages the involvement of patient organisations and scientific societies to help define relevant outcome measures. These usually align with those selected in the pivotal trial. The use of an electronic Case Report Form (eCRF) is strongly recommended to reduce administrative burden and enhance data traceability. Manufacturers are responsible for ensuring data completeness, with a target of less than 10% missing data, and must provide appropriate resources to support prescribers in meeting these obligations. Failure to meet these obligations can jeopardise the renewal of the EAP and negatively influence the pricing and reimbursement (P&R) decision-making process, particularly by shaping HAS’s perception of the treatment’s value and real-world impact. One promising avenue, explored further in Part 3 of this series, is the potential linkage of PUT-RD data with France’s SNDS to streamline collection and improve reliability.
HAS encourages the involvement of patient organisations and scientific societies to help define relevant outcome measures. These usually align with those selected in the pivotal trial. The use of an electronic Case Report Form (eCRF) is strongly recommended to reduce administrative burden and enhance data traceability. Manufacturers are responsible for ensuring data completeness, with a target of less than 10% missing data, and must provide appropriate resources to support prescribers in meeting these obligations. Failure to meet these obligations can jeopardise the renewal of the EAP and negatively influence the pricing and reimbursement (P&R) decision-making process, particularly by shaping HAS’s perception of the treatment’s value and real-world impact. One promising avenue, explored further in Part 3 of this series, is the potential linkage of PUT-RD data with France’s SNDS to streamline collection and improve reliability.
A significant number of Early Access approvals were granted between 2021 and 2024, but the past year has seen a noticeable rise in the number of rejections
Between the second half of 2021 and the first half of 2024, a total of 288 EAP decisions were issued by HAS, including 76 for AP1 (pre-AMM), 96 for AP2 (post-AMM), and 116 for renewals. Among the initial AP1 and AP2 decisions, 122 received favorable opinions while 50 were rejected, representing an average success rate of 70% over the period. However, this marks a decline from the 78% success rate observed between 2021 and 2023, with success dropping to just 50% in the first half of 2024 alone. This decline reflects increasing pressure from NHI, which has criticised HAS for having approved too many EAPs in previous years. Of the 122 favorable decisions, approximately half were for oncology products. Among the 105 products that subsequently underwent reimbursement evaluation, 39% received an ASMR II or III, and 40% received an ASMR IV, indicating that a majority demonstrated at least a moderate level of added clinical benefit. The median evaluation time for EAP applications by HAS was 79 days, and drugs remained in the EAP scheme for an average of 407 days.
In our next articles, we will delve into how the EAP landscape is expected to evolve in the coming years, and explore how the SNDS could enhance real-world evidence generation within the EAP framework.
In our next articles, we will delve into how the EAP landscape is expected to evolve in the coming years, and explore how the SNDS could enhance real-world evidence generation within the EAP framework.
This article summarises Cencora’s understanding of the topic based on publicly available information at the time of writing (see listed sources) and the authors’ expertise in this area. Any recommendations provided in the article may not be applicable to all situations and do not constitute legal advice; readers should not rely on the article in making decisions related to the topics discussed.
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Sources
- European Federation of Pharmaceutical Products (EFPI). Patients W.A.I.T. Indicator 2023 Survey. June 2024. https://efpia.eu/media/vtapbere/efpia-patient-wait-indicator-2024.pdf
- HAS. Autorisation d’accès précoce aux médicaments: doctrine d’évaluation de la HAS. 2022. https://www.has-sante.fr/jcms/p_3274435/fr/autorisation-d-acces-precoce-aux-medicaments-doctrine-d-evaluation-de-la-has
- HAS. Bilan accès précoce 2021 à 2024. October 2024. https://www.has-sante.fr/jcms/p_3555537/fr/bilan-des-acces-precoces-aux-medicaments-288-decisions-en-trois-ans-infographie
- Journal Officiel de la République Française (JOFR). LOI n° 2020-1576 du 14 décembre 2020 de financement de la sécurité sociale pour 2021. December 2020. https://www.legifrance.gouv.fr/jorf/id/JORFTEXT000042665307
- Sénat. Médicaments innovants: consolider le modèle français d'accès précoce. Rapport d'information n°569 (2017-2018). June 2018. https://www.senat.fr/rap/r17-569/r17-5693.html
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