Insights on Early Access Refusal in France

OBJECTIVES: The French Health Technology Assessment agency, Haute Autorité de Santé (HAS), implements an Early Access (EA) program aimed at expediting access to innovative treatments for severe diseases with unmet need. While many therapies are granted EA, some are refused. Understanding the reasons behind refusals within this program is crucial for optimizing future submissions.

METHODS: This retrospective study analyzed all refusal cases within HAS's EA program from 2021 to May 2024. A total of 38 refusal cases were identified on the HAS website and analyzed to discern patterns and insights.

RESULTS: Out of 38, oncology (n=13), hematology (n=9), and dermatology (n=3) emerged as predominant disease areas among refusal cases. HAS consistently evaluated EA submissions based on the seriousness of the disease, availability of alternative treatments, innovation status, and the proposed clinical development plan. Refusals occur if at least one of the criteria is not met. Despite the recognized severity of the diseases, many applications were rejected due to existing alternative treatments (including treatments with EA for similar indications), insufficient evidence demonstrating meaningful benefit over established alternatives, evidence uncertainty due to methodological limitations, and/or lack of a clear clinical development plan. When treatments are available, submitting comparative evidence showcasing benefits over existing treatments will be preferred. However, even unsuccessful EA submissions can yield valuable insights into relevant comparators, guiding future clinical development plans and evidence generation activities to achieve a successful reimbursement outcome.

CONCLUSIONS: This study provides valuable insights into the refusal patterns within HAS's EA program. Understanding the evaluation criteria and strategic considerations can help manufacturers optimize their approaches to navigating the EA landscape and enhance patient access to innovative therapies.