Abstract
While cell and gene therapies (CGTs) have emerged as promising modalities to treat conditions with limited therapeutic options, their unconventional development is fraught with uncertainty, rendering them high-risk assets for many pharmaceutical companies. Here, we assess the clinical development trajectories of CGT products by estimating probabilities of successful clinical trial phase transitions and the likelihood of achieving regulatory approval. We included all CGT products entering clinical development from 1993 to 2023 and intended for marketing in the United States, Europe, Japan, Canada, and Switzerland. Associations between product success and characteristics were investigated. In sub-analyses, we examined the clinical trajectories of two promising product types, chimeric antigen receptor T (CAR T) cell therapies and adeno-associated viral (AAV) vector-based gene therapies. We identified 995 CGT products corresponding to 1,961 development programs. A total of 44 CGTs secured at least one regulatory approval, corresponding to an overall likelihood of approval of 5.3% (95% CI 4.0-6.9). Development programs with an orphan designation had a higher likelihood of approval than those without (9.4%, 95% CI 6.6-13.3 vs. 3.2%, 95% CI 2.0-4.9), while programs for oncology indications had a lower likelihood of approval compared to those for non-oncology indications (3.2%, 95% CI 1.6-5.1 vs. 8.0%, 95% CI 5.7-11.1). CAR T cells and AAV gene therapies had a similar overall likelihood of approval of 13.6% (95% CI 7.3, 23.9) and 13.6% (95% CI 6.4, 26.7), respectively. In conclusion, CGT products have a low overall likelihood of approval with variability based on orphan status, therapeutic area, and product type.