绘制细胞和基因治疗产品的临床发展轨迹。

IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Magdi Elsallab, Michelle Ouvina, Andrea Arfe, Florence T Bourgeois
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引用次数: 0

摘要

虽然细胞和基因疗法(cgt)已经成为一种有希望的治疗方法,可以治疗治疗方案有限的疾病,但它们的非常规开发充满了不确定性,使其成为许多制药公司的高风险资产。在这里,我们通过估计成功的临床试验阶段转换的概率和获得监管部门批准的可能性来评估CGT产品的临床发展轨迹。我们纳入了从1993年到2023年进入临床开发的所有CGT产品,并计划在美国、欧洲、日本、加拿大和瑞士上市。研究了产品成功与特性之间的关系。在亚分析中,我们检查了两种有前景的产品类型的临床轨迹,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。我们确定了995个CGT产品对应1961个开发项目。总共有44个cgt获得了至少一项监管批准,相当于批准的总体可能性为5.3% (95% CI 4.0-6.9)。具有孤儿药认定的开发项目比没有孤儿药认定的项目获得批准的可能性更高(9.4%,95% CI 6.6-13.3 vs. 3.2%, 95% CI 2.0-4.9),而肿瘤适应症项目的批准可能性低于非肿瘤适应症项目(3.2%,95% CI 1.6-5.1 vs. 8.0%, 95% CI 5.7-11.1)。CAR - T细胞和AAV基因疗法的总体批准可能性相似,分别为13.6% (95% CI 7.3, 23.9)和13.6% (95% CI 6.4, 26.7)。总之,基于孤儿状态、治疗领域和产品类型的差异,CGT产品获得批准的总体可能性较低。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mapping the Clinical Development Trajectory of Cell and Gene Therapy Products.

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.

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来源期刊
CiteScore
12.70
自引率
7.50%
发文量
290
审稿时长
2 months
期刊介绍: Clinical Pharmacology & Therapeutics (CPT) is the authoritative cross-disciplinary journal in experimental and clinical medicine devoted to publishing advances in the nature, action, efficacy, and evaluation of therapeutics. CPT welcomes original Articles in the emerging areas of translational, predictive and personalized medicine; new therapeutic modalities including gene and cell therapies; pharmacogenomics, proteomics and metabolomics; bioinformation and applied systems biology complementing areas of pharmacokinetics and pharmacodynamics, human investigation and clinical trials, pharmacovigilence, pharmacoepidemiology, pharmacometrics, and population pharmacology.
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