Advanced Therapy Medicinal Products: The Right Time for Hope?


Pierre Meulien of the Innovative Medicines Initiative (IMI) highlights why cell and gene therapies seem finally braced for mainstream adoption as well as the significant barriers that still need to be overcome for large patient numbers to access these innovative and often costly treatments.


Today, [ATMPs] finally seem to be ready for the prime time, especially in treating single-gene disorders

Gene therapy, somatic-cell therapy and tissue engineering (collectively known as Advanced Therapy Medicinal Products or ATMPs) are all technologies that have been the subject of research for decades. Today, they finally seem to be ready for the prime time, especially in treating single-gene disorders like haemophilia, cystic fibrosis and thalassemia, and of course cell therapies for cancer. However, hurdles remain at every stage of the product research and development cycle and, unless there is more sharing of information and more inter-industrial collaboration, society will not reap the benefits of these potentially groundbreaking treatments.


The proof of concept that gene therapy and cell therapies can work is here now. Research on the genetic basis of rare diseases and immune therapy for certain cancers have changed the lives of a small number of people (these include treatments for retinal dystrophy, spinal muscular atrophy and CAR-T immunotherapy for certain forms of leukaemia). But how can this success be scaled to the point where millions of citizens from any demographic can have access to these innovations at a reasonable cost to our health systems?


The scientific understanding of the aetiology of disease has progressed at a phenomenal pace since the first gene therapy trials took place in 1990 (this was for adenosine deaminase (ADA) deficiency which dramatically impacts the immune system). This new knowledge has not only given rise to new targets for intervention in specific disease settings but has also been invaluable in addressing the safety concerns that have hampered the field for the past three decades. With these technological advantages we can, for example, avoid some of the negative consequences of insertions of introduced genes into the chromosome which give rise to unwanted gene activation. Indeed in early trials of ADA gene replacement, insertional mutagenesis occurred which led to perturbation of cellular proto-oncogene expression and the subsequent generation of a new malignancy.


However, many other hurdles remain to be addressed and these include: understanding the human immune responses against gene delivery vectors; having robust manufacturing platforms that can produce at scale; batch to batch consistency for cell therapies; predicting toxicity for CAR-T technologies; standardising analytical methodologies for product characterisation; and understanding the relative efficacy of integrating versus non-integrating systems. Yes, the list is long!


In addition, there are clinical development and regulatory challenges to be considered which are quite specific to ATMP R&D. Clinical trials for rare diseases for example, often have very small numbers of test subjects and the ethical considerations usually preclude the involvement of a placebo group. The regulatory pathway for authorisation to use a particular intervention is thus very different.


Much is to be said for more cooperation among stakeholders in these challenging areas of research. Just recently, industry players decided to come together through the Innovative Medicines Initiative (IMI) and work collaboratively in a pre-competitive environment to solve these issues by forging collaborations involving a large spectrum of public and private sector players. Indeed, this platform allows patients, regulatory experts, health economists and others to join projects so that their input can be leveraged from the very start of the project. In this way, many blind alleys can be avoided and more efficient and accelerated pathways can be explored.


IMI’s first two Call topics in the ATMP field were launched in June this year. The first, called “Accelerating research and innovation for advanced therapy medicinal products”, will have an overall budget of around EUR 30 million and will tackle a range of issues that currently hamper the development of treatments for rare diseases. As mentioned above, rare diseases are an area where ATMPs could make a big difference to patients’ lives. The second programme, “Supporting the development of engineered T-cells”, will have a budget of EUR 17.5 million and will focus on the preclinical space in CAR-T cell therapy development.


Both of these topics demonstrate that the pre-competitive landscape changes over time (could we have imagined five years ago that Servier, Bayer, J&J and Takeda would cooperate in this field?) and that public-private partnerships are excellent vehicles that can both de-risk investments for the private sector and accelerate access to innovation for patients in need.

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