Catching Them Early: Framework Parameters and Progress for Prenatal and Childhood Application of Advanced Therapies

Abstract

Advanced therapy medicinal products (ATMPs) are medicines for human use based on genes, cells or tissue engineering. After clear successes in adults, the nascent technology now sees increasing pediatric application. For many still untreatable disorders with pre- or perinatal onset, timely intervention is simply indispensable; thus, prenatal and pediatric applications of ATMPs hold great promise for curative treatments. Moreover, for most inherited disorders, early ATMP application may substantially improve efficiency, economy and accessibility compared with application in adults. Vindicating this notion, initial data for cell-based ATMPs show better cell yields, success rates and corrections of disease parameters for younger patients, in addition to reduced overall cell and vector requirements, illustrating that early application may resolve key obstacles to the widespread application of ATMPs for inherited disorders. Here, we provide a selective review of the latest ATMP developments for prenatal, perinatal and pediatric use, with special emphasis on its comparison with ATMPs for adults. Taken together, we provide a perspective on the enormous potential and key framework parameters of clinical prenatal and pediatric ATMP application.

Beta thalassemia: Looking to the future, addressing unmet needs and challenges

“…More efficient and affordable therapy is possible through in utero or pediatric treatments, the early application of which is fundamental to the treatment of many as-yet untreatable diseases with pre-or perinatal onset. 50 All of these aspects of good governance are based on the experience and evidence provided by successful national programs applied to a few high-prevalence yet high-resource countries, such as Italy, Greece, the UK, and other Western nations. In these countries, patients are surviving long enough to be active members of society.…”

“…More efficient and affordable therapy is possible through in utero or pediatric treatments, the early application of which is fundamental to the treatment of many as‐yet untreatable diseases with pre‐ or perinatal onset 50 …”

Pediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies

“…Regarding the MAA of ATMPs for the pediatric age, they faced the same routes of application as in adults [25], with crucial regulatory support provided in the Pediatric Regulation, Regulation (EC) No 1901/2006 and its amendment (EC) No 1902/2006. Recognizing the shortfall of pediatric treatments, the Pediatric Regulation offers incentives such as those stated in the pediatric-use marketing authorization (PUMA), access to the EMA-specific pediatric expert committee, and free advice to the industry.…”

“…ATMPs are a heterogeneous group of biopharmaceuticals encompassing gene therapy, somatic cell therapy, tissue-engineering, and their combination. These nascent technologies have the potential to reduce or repair disease-causing cells, thereby introduc-ing a curative approach to address the unmet medical needs and highlighting personalized precision medicine [24], with promising applications in the pediatric population [25].…”

Providing Australian children and adolescents with equitable access to new and emerging therapies through clinical trials: a call to action

“…Recently, numerous life‐changing and life‐saving therapies have emerged, with many more in the drug development pipeline (Box 1). 1‐4 Phenotypic drug discovery has been revolutionised by advanced methods for pre‐clinical screening: disease models using induced pluripotent stem cell technologies, organoids, gene‐editing tools and imaging assay technologies 5 . Between 2010 and 2020, 440 innovative drugs were approved for marketing by the United States Food and Drug Administration, 2 including an increasing number of gene and other advanced therapeutics 1 .…”