Elsallab Magdi, Ouvina Michelle, Arfe Andrea, Bourgeois Florence T
Harvard-MIT Center for Regulatory Science, Harvard Medical School, Boston, Massachusetts, USA.
Cellular Immunotherapy Program, Mass General Cancer Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Clin Pharmacol Ther. 2025 May;117(5):1264-1271. doi: 10.1002/cpt.3512. Epub 2024 Dec 10.
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.
虽然细胞和基因疗法（CGT）已成为治疗选择有限的疾病的有前景的治疗方式，但其非常规的开发充满不确定性，使其成为许多制药公司的高风险资产。在此，我们通过估计临床试验阶段成功过渡的概率以及获得监管批准的可能性来评估CGT产品的临床开发轨迹。我们纳入了1993年至2023年进入临床开发并打算在美国、欧洲、日本、加拿大和瑞士上市的所有CGT产品。研究了产品成功与特征之间的关联。在亚分析中，我们研究了两种有前景的产品类型，嵌合抗原受体T（CAR T）细胞疗法和基于腺相关病毒（AAV）载体的基因疗法的临床轨迹。我们确定了995种CGT产品，对应1961个开发项目。共有44种CGT获得了至少一项监管批准，总体批准可能性为5.3%（95%置信区间4.0 - 6.9）。有孤儿药指定的开发项目比没有的更有可能获得批准（9.4%，95%置信区间6.6 - 13.3对3.2%，95%置信区间2.0 - 4.9），而肿瘤学适应症项目获得批准的可能性低于非肿瘤学适应症项目（3.2%，95%置信区间1.6 - 5.1对8.0%，95%置信区间5.7 - 11.1）。CAR T细胞疗法和AAV基因疗法的总体批准可能性相似，分别为13.6%（95%置信区间7.3，23.9）和13.6%（95%置信区间6.4，26.7）。总之，CGT产品总体批准可能性较低，且因孤儿药状态、治疗领域和产品类型而异。
