A Bayesian Approach for Selecting Relevant External Data (BASE): Application to a study of Long-Term Outcomes in a Hemophilia Gene Therapy Trial

Gene therapies aim to address the root causes of diseases, particularly those stemming from rare genetic defects that can be life-threatening or severely debilitating. While there has been notable progress in the development of gene therapies in recent years, understanding their long-term effectiveness remains challenging due to a lack of data on long-term outcomes, especially during the early stages of their introduction to the market. To address the critical question of estimating long-term efficacy without waiting for the completion of lengthy clinical trials, we propose a novel Bayesian framework. This framework selects pertinent data from external sources, often early-phase clinical trials with more comprehensive longitudinal efficacy data that could lead to an improved inference of the long-term efficacy outcome. We apply this methodology to predict the long-term factor IX (FIX) levels of HEMGENIX (etranacogene dezaparvovec), the first FDA-approved gene therapy to treat adults with severe Hemophilia B, in a phase 3 study. Our application showcases the capability of the framework to estimate the 5-year FIX levels following HEMGENIX therapy, demonstrating sustained FIX levels induced by HEMGENIX infusion. Additionally, we provide theoretical insights into the methodology by establishing its posterior convergence properties.