Adoptive cell therapy for treatment of rare diseases and orphan designation.

Abstract

Abstract Adoptive cell therapies exploit the body’s immune system to target and treat oncological conditions. Many substances are developed to treat rare haematological malignancies which fulfil the criteria for being considered as orphan conditions according to the EU Orphan Regulation (1-2). Chimeric antigen receptor (CAR)-T cell products belong to this group of therapy. The Committee for Orphan Medicinal Products has reviewed 23 adoptive cell therapies which were associated with 36 different applications for orphan designation (OD) over a 10-year period, and nineteen of these were CAR-T cell products intended to treat various rare conditions. Most of these products were developed for the treatment of rare haematological malignancies. Preliminary clinical data was used in 80% (29/36) of the OD submissions to support medical plausibility (promise of efficacy) of the candidate products and an assumption of significant benefit, which is the added benefit of the new product over currently authorised medicines for the proposed orphan condition. Eighty-nine percent (32/36) cases of significant benefit were accepted based on a clinically relevant advantage. Twelve of fourteen submissions reviewed for maintenance of the OD at time of marketing authorisation or extension of indication demonstrated significant benefit of the products over existing therapies within the approved therapeutic indications, but one of these were withdrawn during the evaluation. In conclusion, adoptive cell immunotherapy is a dynamic field in the treatment of haematological malignancies. In the case of applications and ODs granted by the European Commission, autologous CAR-T cell products using a lentiviral vector represent most of the submissions, while CD19 was the most frequently targeted antigen. Clinical data was the most common type of data taken into account at the time of initial OD to support medical plausibility. A high rate of successful initial ODs for these products also seem to translate into a high success rate at the time of marketing authorisation or extension of indication.