Date of Award

Fall 12-2023

Document Type


Degree Name

Doctor of Philosophy (PhD)


Pharmaceutical Sciences

First Advisor

Enrique Seoane-Vazquez

Second Advisor

Lawrence M. Brown

Third Advisor

Marc L. Fleming

Fourth Advisor

Rosa Rodriguez-Monguio


Background: Gene therapy has recently emerged as an alternative for preventing and treating disease. Concerns have been expressed about the clinical value and the high cost of gene therapies.

Objective: This study assessed the authorization process of gene therapy products by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), evaluated the post-marketing safety signals reported to the FDA Adverse Event Reporting System (FAERS), and assessed the cost-effectiveness analysis of three gene therapies axicabtagene ciloleucel(axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel).

Research Design: For aim 1; data was collected using regulatory information from the FDA and the EMA websites, US National Library of Medicine and the EU Clinical Trials Register, the US Red Book, UK National Institute for Health and Care Excellence, and the German Institute for Quality and Efficiency in Health Care. Descriptive statistics and t-tests were conducted in the study. For aim 2; data was collected from the FDA website. A retrospective pharmacovigilance analysis was carried out on adverse events (AEs) reports from the FAERS database. For aim3; data were extracted from the pivotal clinical trials, US Red Book, Centers for Medicare and Medicaid Services, and existing literature. Quality-adjusted life years (QALYs) and incremental vi cost-effectiveness ratios (ICERs) were calculated. Statistical analyses for all aims were conducted using Microsoft Excel and R version 4.0.5.

Results: As of January 1, 2022, the FDA and EMA authorized 8 and 10 gene therapies, respectively. Pivotal clinical trials were non-randomized, open label, uncontrolled, phase I-III, and included a limited number of patients. The price of gene therapies at market entry ranged from $200,064 to $2,125,000. Except for voretigene neparvovec, all drugs had a higher percentage of serious than non-serious AEs (> 56.6%). Reporting odds ratios varied depending on the condition, alternative used, and whether it was used as a single drug or in combination with other active ingredients. Axi-cel, liso-cel, and tisa-cel cost $541,025.80, $491,758.80, and $463,368.41 per patient, respectively. Total QALYs for axi-cel were similar to those for liso-cel (4.57 versus 4.49), but higher compared to tisa-cel (4.57 versus 2.02). The incremental costs per QALY gained for axi-cell were $615,069 vs. liso-cel and $30,534 vs. tisa-cel.

Conclusions: Gene therapy is being authorized with limited clinical evidence to ensure safety and efficacy. The use of a gene therapy regimen was associated with lower odds of serious vs. non serious AEs reported to FAERS compared to the status quo regimen. Despite the comparable efficacy profile between axi-cel and liso-cel, liso-cel seems to be the most cost-effective alternative.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Available for download on Wednesday, January 01, 2025