OBJECTIVES: Gene therapy has the potential to transform patients’ lives and appropriate assessment methods are needed to capture the benefits of this type of treatment. The objective of this research was to characterize the current use of clinical outcome assessments (COAs) for U.S. Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved gene therapies to describe ways in which the gene therapy patient experience is captured.

METHODS: A review of regulatory documentation was conducted for gene therapies approved by the FDA and the EMA; this was supplemented by a targeted grey literature search (via Google Scholar, PubMed, and clinicaltrials.gov) to identify how COAs were used to support drug development. The pre-specified search included therapies for the treatment of inherited conditions and excluded cell therapies (e.g., intended as regenerative treatments). Full-text documents were reviewed to identify the COAs administered, describe their usage, and document instances where COAs have been utilized to support label claim.

RESULTS: Two gene therapy products were approved by the FDA for inherited retinal disease and spinal muscular atrophy. COAs were used in drug development trials and to support label claims for both products (utilizing a clinician-reported outcome and performance outcome [PerfO], respectively). Four gene therapy products were approved by the EMA for lipoprotein-lipase deficiency, severe combined immunodeficiency due to adenosine deaminase deficiency, transfusion-dependent beta thalassemia, and inherited retinal disease. Of these, two used COAs during drug development (utilizing a patient-reported outcome and a PerfO [which was used to support the primary efficacy endpoint]). Some products used COAs in post-approval studies.

CONCLUSIONS: While a limited number of gene therapies have been approved by the FDA and EMA; encouragingly, COAs were used during their development. Future research should continue to explore ways for COAs to capture the treatment benefit for these potentially transformative therapies.