Accelerating research & innovation for advanced therapy medicinal products

The main focus of this topic is to develop a product characterisation framework and methodologies that are limited to the pre-competitive space. Though much of the work will be to understand aspects of gene or cell therapy in general without a particular disease focus, there may be some work that utilises disease models to accomplish the appropriate characterisation. The disease focus will be on non-oncological, monogenic rare diseases. Therefore, this topic intends to utilise both therapeutically relevant systems, as well as model systems that rely on the use of marker transgenes. In order to develop such a framework, there is a need for a coordinated and substantive effort to acquire and analyse the currently available data and then design preclinical and clinical studies to fill the knowledge gaps. This information will help to address gene/cell therapy risks and also guide product developers and regulators to determine and implement an appropriate and effective characterisation framework to enable efficient and safe development of gene/cell therapies.

The main objectives of the topic, intended to address existing knowledge/data and tools gaps focused on viral-mediated gene therapy and cell therapy, are to:

1) develop better, standardised models for predicting product immunogenicity in humans;

2) build our understanding of gene/cell therapy drug metabolism inside a host and explore any loss of efficacy (persistence), particularly with non-integrating viral vectors or cell therapy;

3) understand the clinical factors around pre-existing immunity limiting patient access to ATMP therapy, and adaptive immune responses affecting product safety, efficacy and persistence, including for integrating vectors-based therapies;

4) engage regulators to ensure that the models and data generated through the funded action will provide the necessary information to support regulatory filings and to address regulatory and safety concerns.

Curative or near curative therapies for rare and orphan diseases have been a long-held desire for many in the biomedical research and development arena, including patients. Rare diseases are often very severe, genetically driven illnesses with high morbidity and mortality that place a large burden on families of patients and healthcare systems. Gene therapy and cell therapy provide an opportunity for a curative, single treatment for many of these devastating diseases, eliminating the need for chronic treatment. This topic aims to accelerate the research and development of advanced therapy medicinal products (ATMPs) by filling gaps in our knowledge base in, and tools for, gene and cell therapy. This will provide medicines developers and regulators with the information they need to more swiftly move these potentially transformative medicines forward so that they can benefit patients in need.

Conventional medicinal product characterisation, clinical safety/efficacy, and regulatory requirements already pose challenges to developing treatments for rare monogenic diseases. These challenges are amplified for gene and cell therapies due to knowledge gaps in our understanding of these ATMPs for viral or non-viral approaches. By addressing these existing knowledge gaps, we hope to accelerate and improve the feasibility of product development and decrease development time and costs to bring effective new advanced therapies to patients. For many aspects of ATMP biology and safety, regulatory agencies have to consider theoretical concerns in this emerging field, largely due to a lack of supporting data and evidence. This can be a major burden for the efficient development of ATMPs.

Primarily, the action funded under this topic will fill gaps in our knowledge base around gene/cell therapy host responses, which will allow for the data-driven development of a product characterisation framework to aid researchers, developers and regulators to more rapidly move effective and safe gene/cell therapies forward.

Understanding the host immune responses and the prevalence of pre-existing immunity in humans in broad geographic areas will be instrumental for finding the best immune-modulating regimens, thus increasing patient access to advanced medicines. Understanding the determinants of immunogenicity may enable re-dosing with gene/cell therapy products, while studying the mechanisms of persistence will help to define the optimal age for gene/cell therapy intervention.

Finally, joint efforts across pharma, biotech, academia, and regulatory functions will inform patient inclusion criteria, limit sub-therapeutic dosing, and define the impact of the pre-existing and adaptive immunity on the efficacy and persistence of gene/cell therapy. This broad understanding will help to focus industry resources on actual (not theoretical) risks and will facilitate the harmonisation of regulatory requirements. These improvements will, in turn, enable accelerated cures for rare diseases via a defined regulatory framework.