In the first blog of this series, our Senior Associate, Sama Seyedmousavi, explored the global landscape of early access pathways, shedding light on their structure and function. The second blog delved into the core building blocks of these pathways and how they operate. Now, in this blog, she takes a closer look at France’s Early Access Program – Autorisation d’Accès Précoce (AAP), evaluating the opportunities and risks that each building block presents for manufacturers. Overall, this deep dive into the French AAP serves as a practical case study, helping manufacturers understand how to apply the 10 building blocks, associated features and design options when evaluating early access opportunities, not just in France but across complex early access pathways globally.
Dissecting the French AAP: A strategic case study for manufacturers
France is a trailblazer in early access pathways, being the first country to establish a legal framework for them. Moreover, as the most advanced early access pathway in Europe, the French AAP is highly regulated and covered by social insurance. It allows for temporary reimbursement of products awaiting marketing authorisation (MA) and/or routine reimbursement, specifically for patients who have exhausted all other treatment options.
This blog breaks down each building block of the French AAP, analysing where the opportunities lie and what risks or strategic considerations manufacturers should keep in mind as they navigate this pathway.
1. Pathway initiation
Manufacturers can trigger AAP once pivotal (Phase 2/3) data are available, allowing them to seek access well before MA. The pathway has two forms:
- AAP1 applies to products without MA, requiring consultation with Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) prior to Haute Autorité de Santé (HAS) assessment.
- AAP2 applies post-MA and is handled solely by HAS.
Opportunity: AAP provides an opportunity to offer treatment based on pivotal trial data, enabling prescribers to gain early experience with a novel treatment.
2. Pathway coverage
AAP covers patient cohorts, with HAS typically makes the decision within 3 months, for a duration of 1 year, and with the possibility of renewal based on an updated dossier and data.
Opportunity: Broad coverage for cohort-level access can increase patient reach and build early recognition with HCPs and the system.
Risk: Annual renewal creates an administrative workload for both manufacturers and the Haute Autorité de Santé (HAS).
3. Therapy characteristics
AAP is intended for treatments targeting serious, rare, or debilitating diseases. In line with this, HAS grant access based on preliminary evidence and unmet need, across first or follow-on indications.
Opportunity: AAP provides timely access for patients with a high unmet need, allowing them access to treatments in or just out of clinical development.
4. Pathway funding
AAP is fully funded by France’s Social Security system, with no out-of-pocket costs for patients.
Opportunity: Guaranteed public funding provides an opportunity for early financial return on investments.
5. Product pricing
Manufacturers set the price freely during AAP, without negotiations or application of international reference pricing (IRP). However, authorities apply a payback to cover the difference between the early access price and the negotiated price for routine reimbursement. Furthermore, the French clawback system also applies to products in the AAP, and the early access price can informally set the benchmark for future negotiations. Once in routine pricing and reimbursement (P&R), annual renegotiations begin.
Opportunity: No price caps during AAP, enabling early revenue potential.
Risk: Authorities apply a payback to the difference between the prices in early access and routine P&R. Initial prices may shape future P&R expectations and limit negotiation flexibility with Comité Economique des Produits de Santé (CEPS).
6. Data opportunities
Low clinical evidence is acceptable at entry, including Phase 2 data (only for rare diseases). Healthcare providers are primarily responsible for collecting mandatory data with no financial support from manufacturers.
Opportunity: The AAP supports early access despite clinical uncertainty, functioning as a coverage-with-evidence approach that allows access to treatment while additional data is generated.
Risk: Suboptimal organisation of data collection frequently leads to insufficient data quality for informing routine P&R decisions, thereby limiting its utility.
7. Data obligations
Manufacturers must submit annual dossiers that include safety and efficacy updates.
Risk: Annual safety and efficacy updates create a high administrative burden, requiring regular updates and coordination with HAS.
8. Continuity obligations
Manufacturers must be ready to ensure product supply within 2 months of pathway initiation. Furthermore, to enter AAP1, the manufacturer needs to commit to file for MA within 2 years. In parallel, HAS can terminate the pathway based on new data. If routine P&R is rejected after the AAP, manufacturers must continue providing the product free of charge for one year.
Risk: Tight timelines make supply planning difficult, especially when approval is uncertain. In the event of AAP termination by HAS and/or a negative P&R decision, the manufacturer must provide the treatment free of charge to patients for 1 year.
9. Chances of success
The pathway is widely used, but approval depends on strong data and a clear unmet need.
Risk: Lower success rates increase the risk of sunk effort.
10. Pathway governance
French authorities govern the AAP by well-documented and transparent procedures and performance reports.
Opportunity: Clear guidelines and structured governance reduce ambiguity for applicants.
Figure 1: Ten building blocks of France’s Autorisation d’Accès Précoce (AAP)
Have an asset that may benefit from early access, but not sure where to start?
For manufacturers, early access pathways can offer significant strategic and product-specific advantages. This is only possible when their complexity is fully understood. The specific design of each pathway shapes market-by-market and product-by-product opportunities and risks.
Regardless of your development stage, whether you’re evaluating which pathway fits best or which market offers the right opportunity, understanding the potential risks and advantages is essential to making informed strategic choices.