OBJECTIVES: In France, patients can benefit an early access to innovation, ahead of the marketing authorization or final reimbursement since 1992. This early access program (EAP) was reformed on July 1, 2021. As of this date, the eligibility criteria, the agency responsible for EAP granting, the timelines and the process have evolved. Medicines indicated in a severe, rare or disabling disease, are eligible to EAP when there is no suitable treatment available on the market, when efficacy and safety are presumed and when the product is considered presumed innovative. Our study aimed identifying (1) the reasons for not granting EAP and (2) the impact on market access in France.

METHODS: We conducted a retrospective analysis of all HAS decisions published between July 1, 2021 and Avril 21, 2022 that resulted in an early access denial.

RESULTS: Among 47 EAP evaluations, 10 refusals (21%) were identified. In total, the most represented therapeutic areas were oncology (40%) and infectiology (30%). It was a initial assessment by the HAS for 70% of refused treatments. 10% were medicines not indicated in severe, rare or disabling disorders. Appropriate comparators were identified for 70%, highlighting a partially met medical need. Efficacy and safety were not presumed for 10% and 60% were not presumed innovative by the HAS. Finally, 5/10 medecines where evaluated for reimbursement in France. Of these, 4 were reimbursed, all in a restricted indication compared to the requested EAP indication. The TC granted an important (1/4), moderate (1/4) or low (2/4) SMR, all associated with an ASMR V.

CONCLUSIONS: The most common criteria leading to early access refusal was the absence of appropriate comparators, not reached in 70% of refused medicines. Denial of EAP appears to be predictive of achieving ASMR V and not significant or even insufficient SMR (no reimbursement).