OBJECTIVES: : France has a long lasting experience in early-entry program (ATU). About 30,000 patients get access to innovative therapies through ATU every year. Eligible medicines need to target a severe condition, with no therapeutic alternative and have strong signal of favorable benefit risk ratio. Nominative ATU (nATU) intent to address unmet medical need of one specific patient. Some theoretical gaps in patient access may occur after marketing authorization as nATU is interrupted at this time. The objective of this study is to identify if disruption in patient access occurs in practice after nATU’s end.

METHODS: Based on experts’ knowledge and desk research, we identified medicines that benefited from nATU program but failed to achieve reimbursement post approval. HTA assessment, ASMR, SMR and size of targeted populations was extracted from French HTA body (HAS) website.

RESULTS: We identified 6 medicines with nATU that ended after approval with no settled funding or reimbursement, thus disrupting patient access: Kolbam^® (cholic acid), Kyprolis^® (carfilzomib), Defitelio^® (defibrotide), Besponsa^® (inotuzumab ozogamicin), Opdivo^® (nivolumab) and Xofigo^® (Radium-223 Dichloride). Targeted indications (7) were very rare: five were targeting less than 300 patients per year and less than 3,700 for the two others. Only three indications obtained an important SMR; one moderate, one low and two insufficient. Three indications obtained an ASMR IV and two ASMR V. One company provided the product for free to allow treatment continuation. One product already approved for other indications may potentially be used off reimbursement, and the four other products are not accessible post approval.

CONCLUSIONS: These cases highlight the gap between nATU granting and later reimbursement or funding decisions. French nATU process may be too generous opening early access for drugs supposed to be unavoidable that later are considered not-reimbursable. It is paradoxical that products are accessible before approval and not post approval.