PHP44 - Risk of Discontinuation of Advanced Therapy Medicinal Products Clinical Trials

Abstract

Advanced Therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses: gene therapy, somatic cell therapy and tissue engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field. Randomized clinical trials (RCT) generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation. We searched for ATMPs trials conducted between 1999 to June 2015 using three databases: Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP) and the EudraCT. We selected the ATMPs trials after elimination of duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organization. We classified ATMPs by type and trial status: ongoing, completed, terminated, discontinued, and prematurely ended. Then we calculated the rate of discontinuation. 143 withdrawn, terminated or prematurely ended ATMPs clinical trials were identified between 1999 and June 2015 and 474 ongoing and completed clinical trials. Therefore, the rate of discontinuation of ATMPs trials is 23.17% similar to non-ATMPs drugs in development. The probability of discontinuation is respectively 27.35%, 16.28%, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (44%) followed by cardiology and immunology/inflammation (22.2%). It is almost the same for commercial and non-commercial sponsors (24%); Suggesting discontinuation may not be financially driven. No failure risk rate per development phase is available for ATMPs. Discontinuation rate may prove helpful when assessing expected net present value to support portfolio arbitration. These results carry limitation as the reason for discontinuation is unknown. Further research about the reasons of discontinuation and the risk of negative results is needed to inform manufacturers and investors decisions.