BACKGROUND: On July 1^st 2021, France’s Social Security Financing Law implemented the Early Access Program (AAP), formerly the ATU, allowing early access to medicines. Manufacturers benefit from free pricing upon AAP entry, however they face retrospective rebates if the final negotiated price is lower than the maximum fee charged during the AAP.

OBJECTIVES: This study compares the prices of orphan and ultra-orphan medicines during AAP participation and following exit over the past three years in France, to understand pricing dynamics, with a particular focus on reference pricing.

METHODS: Early access authorization tables from June 2021 to February 2024 were reviewed, specifically for orphan and ultra-orphan medicines acknowledged by the European Medicines Agency. Products with prices listed in both the authorization table (AAP price) and in the Official French Gazette (reimbursed price) were selected for analysis and compared against respective prices in Germany.

RESULTS: In the last three years, 78 orphan medicines have been listed on the early access authorization tables in France. Of these, 39 have been fully reimbursed, with an average price reduction of 16% observed from AAP entry to exit. Price reductions are typically driven by referencing the negotiated price in Germany post-benefit assessment. In total, 27 of 39 medicines incurred a price reduction of more than 10%, 6 had a reduction of 0-10%, and 6 achieved an increase in price.

CONCLUSIONS: An attractive option for launching high-cost, rare disease medicines in France is the AAP. Despite flexible pricing, prices often decrease following AAP exit due to reference pricing, often focused on Germany. Our analysis supports the importance of considering pricing implications in early access programs as part of French Health Technology Assessment (HTA) strategy.