# Navigating the orphan medicinal product designation: Evidence requirements for gene therapies in Europe

## TL;DR

This paper analyzes the data used to support orphan drug designations for gene therapies in Europe, focusing on evidence requirements and submission patterns.

## Contribution

The study provides insights into the regulatory acceptance of non-clinical and clinical data for gene therapy orphan designations.

## Key findings

- Most applications used non-clinical in vivo data, often from mouse models, to support orphan designations.
- Only 13% of applications included clinical data, typically from early-stage trials with few patients.
- Half of the non-clinical data relied on surrogate endpoints, and 54% of submissions met the significant benefit criterion.

## Abstract

To provide insight into regulatory decision-making at the time of granting initial orphan designation by the Committee for Orphan Medicinal Products, we have conducted a retrospective analysis for viral vector-mediated gene therapies in rare non-oncological conditions with respect to the data provided to support the criteria to be met in successful applications. We found that a high proportion of non-clinical in vivo data was used for gene therapies, indicating earlier submissions of products that are at the stage of preclinical research and not in clinical development. Clinical data were submitted in only 13% of the applications, containing preliminary results derived from early-stage clinical trials in few patients. Mouse models were used in the majority of the submissions to generate meaningful non-clinical in vivo data highlighting their utility for proof-of-concept studies, and half of the applications containing non-clinical data generated results based solely on surrogate endpoints. The criterion of significant benefit was applicable in 54% of the submissions, which indicates that sponsors are focusing gene therapy development in areas of high unmet medical need, particularly where there are no authorized medicines available.

Palomo, Mariz, and colleagues describe the data submitted in successful applications for orphan designation for viral vector-based gene therapy products in rare non-oncological conditions. A description of the particularities and acceptance of the data to support two important orphan designation criteria might benefit product developers in future applications.