Advanced therapy medicinal products: current and future perspectives

Abstract

BackgroundAdvanced therapy medicinal products (ATMPs) are innovative therapies that encompass gene therapy, somatic cell therapy, and tissue-engineered products. These therapies are expected to bring important health benefits, but also to substantially impact the pharmaceuticals budget.ObjectiveThe aim of this study was to characterise the ATMPs in development and discuss future implications in terms of market access.MethodsClinical trials were searched in the following databases: EudraCT (EU Drug Regulating Authorities Clinical Trials), ClinicalTrials.gov, and ICTRP (International Clinical Trials Registry Platform of the World Health Organization). Trials were classified by category of ATMP as defined by European regulation EC No. 1394/2007, as well as by development phase and disease area.ResultsThe database search identified 939 clinical trials investigating ATMPs (85% ongoing, 15% completed). The majority of trials were in the early stages (Phase I, I/II: 64.3%, Phase II, II/III: 27.9%, Phase 3: 6.9%). Per category of ATMP, we identified 53.6% of trials for somatic cell therapies, 22.8% for tissue-engineered products, 22.4% for gene therapies, and 1.2% for combined products (incorporating a medical device). Disease areas included cancer (24.8%), cardiovascular diseases (19.4%), musculoskeletal (10.5%), immune system and inflammation (11.5%), neurology (9.1%), and others. Of the trials, 47.2% enrolled fewer than 25 patients. Due to the complexity and specificity of ATMPs, new clinical trial methodologies are being considered (e.g., small sample size, non-randomised trials, single-arm trials, surrogate endpoints, integrated protocols, and adaptive designs). Evidence generation post-launch will become unavoidable to address payers’ expectations.ConclusionATMPs represent a fast-growing field of interest. Although most of the products are in an early development phase, the combined trial phase and the potential to cure severe chronic conditions suggest that ATMPs may reach the market earlier than standard therapies. Targeted therapies have opened the way for new trial methodologies, from which ATMPs could benefit to get early access. ATMPs may be the next source of major impact on payers’ drug budgets.

Exosomes as Reconfigurable Therapeutic Systems

“…The European Union and United States regulatory agencies consider human exosome-based therapeutics as biological medicinal products, and, depending on pre- or post-isolation manipulations -- such as the genetic-manipulation or cell expansion of parent cells -- might be classified as advanced therapy medicinal products (ATMPs) [58]. When compared to MSC therapies, exosomes might be able to overcome safety concerns surrounding continued MSC proliferation, whilst having the same therapeutic effect.…”

Esophageal tissue engineering: from bench to bedside

“…For instance, decellularized scaffolds or any other biomaterials alone would fall into the category of medical devices, and thus validation of the product would require analyses to determine product sterility, biomechanical properties, and scaffold stability in the body . Additionally, cell sheets or a combination of cells and a scaffold can be categorized as Advanced Therapy Medicinal Products, meaning that they are “medicines based on genes, tissues, or cells, offering groundbreaking new opportunities for the treatment of disease and injury.” These types of products are highly regulated and require further thorough analysis to determine the reproducibility of the procedure, state of the cells alone or on a scaffold, their genomic stability, their distribution in the body once transplanted, and their outcome in a complex biological environment.…”

Manufacturing process development of ATMPs within a regulatory framework for EU clinical trial & marketing authorisation applications

“…To illustrate how the principles discussed above apply to real-world ATMP development programs [40], considerations for manufacturing ATMPs from donated tissue or banked cell starting materials will be outlined. These considerations will also need to take into account whether the manufacturing process is based on a scale-out (small batch size; e.g., autologous products, one batch per patient) or scale-up (large batch size; e.g., allogeneic products, multiple identical doses per batch) approach, and the specific bioprocessing technologies involved [1].…”