The View from the Commission
Arnd Hoeveler, Head of Unit for Advanced Therapies and Systems Medicines, DG Research and Innovation
Europe is currently a world leader in the fundamental science underpinning regenerative medicine and cell therapy, and in its therapeutic use and regulation. But how can Europe build on its leading position?
The Commission’s approach to regenerative medicine research in Horizon 2020 is based on its assessment that this is a high value technology that will deliver life-changing treatments.
However, a huge barrier – in the shape of the lengthy development timelines – lies in the way of realising this potential. An analysis of the advanced therapies clinical trials coming before the European Medicines Agency shows they are mostly sponsored by academics and SMEs, indicating the need for public sector support.
The Commission wants to support more clinical trials in Horizon 2020 to take products through from preclinical development to proof of principal in humans, providing showcases for the technology and examples of the therapeutic power.
At the same time it is necessary to put the focus on medical need and expand the range of therapies that are being developed. “We need to get cell therapies to more patients and build up safety and efficacy data,” Hoeveler said.
Horizon 2020 contains proposals for new funding schemes and instruments for SMEs. The intention is to give small high-tech companies access to support for each stage of development, from the exploratory phase, to clinical trials, scale-up and commercialisation. While the European Union will not directly finance commercialisation activities, it intends to make it easier to access finance, for example, through loan guarantees and risk-sharing mechanisms, so that SMEs will be able to take their products through to market.
The EU has the regulatory framework in place to underpin this, Hoeveler noted, in the shape of the European Medicines Agency’s Committee for Advanced Therapies, which has built up considerable skills and expertise since coming into operation in 2007. To date, two advanced therapy products have been approved, ChondroCelect, a cell therapy derived from a patient’s own cells, for treating damaged knee cartilage, and Glybera, a gene therapy for treating a rare metabolic disorder.
In addition, the Commission has just put forward two regulatory proposals, the regulation on Clinical Trials, which aims to make it easier to set up clinical trials, and new regulations for medical devices and diagnostics. This is relevant for the new sector because regenerative medicine is not a single, standalone technology, but draws on a range of tools and devices in a complex evolving regulatory framework. “The interlink between different areas is extremely important", Hoeveler said.
The View from a translational expert
Keith Thompson, CEO, Cell Therapy Catapult Centre, UK
Thirty years ago monoclonal antibodies were a laboratory curiosity, now they represent one of the most therapeutically useful and commercially successful classes of drugs. “The conversations I’m are having now about commercialising cell therapies are the same as those I was having about monoclonal antibodies at the start of my career,” Thompson said.
In common with CellforCure in France, the Cell Therapy Catapult Centre has been set up to fill in the missing pieces, in scale-up, repeatability, manufacturing, establishing supply chains, and so on, that are needed to commercialise cell therapies. “We don’t have all the answers as yet, but we do have the collective will to get the field going, and I’m confident we will bring an array of therapies to market over time,” said Thompson.
A number of early, experimental treatments hint at what is at possible: a diabetic who received a pancreatic islet cell transplant was able to stop administering insulin within two weeks; autologous transplants of corneal epithelial stem cells are routinely used to repair injured corneas. Meanwhile, a research project that aims to generate red blood cells from embryonic stem cells and scale-up to an approved manufacturing process is making good progress.
The aim of the Cell Therapy Catapult Centre is to provide further demonstrations of how stem cells can address unmet medical need, improving health and creating a resilient commercial sector.
To achieve this, four elements must be advanced in parallel, Thompson said:
- Advancing the fundamental science
- Moving products into clinical trials
- Addressing manufacturing and supply chain issues, bringing down the cost of goods, and working on mechanisms and devices for administering therapies
- Developing business models
The Cell Therapy Catapult Centre has government funding of £10 million per annum over five years, to be matched by funding from collaboration partners. It will use this to:
- Provide people and laboratories to take on projects and take them into clinical trials and de-risk them to the point where it will be possible to attract further investment
- Work on manufacturing issues in collaboration with industry, providing businesses with access to intellectual property and regulatory expertise
- Set up a contract research service
- Compile and maintain a database of clinical activity in the field
The objective is to “create the climate which will draw in major investment that will be required by big pharma to commercialise cell therapies,” Thompson concluded.
The view from Europe’s largest medical research charity
Katherine Littler, Policy Adviser, Wellcome Trust
As the largest charitable funder of research in Europe (and the second largest in the world), the Wellcome Trust takes an active interest in ensuring that the regulatory environment fosters the translation of the science that it funds.
In regenerative medicine and cell therapy the regulatory system needs to provide:
- Certainty – without this people will not invest
- Clarity – researchers are happy to respect the rules if they are clear. This sounds straightforward, but can be difficult to achieve
- Proportionality – there is a need to weigh any risks against the public benefits
- Streamlined rules – if regulations are too complicated or time-consuming to follow, companies and investors will go to other regions of the world, which have both the expertise and appropriate but flexible regulatory frameworks
- Harmonisation – while upholding the principal of subsidiarity, harmonised rules and standards are key in underpinning research and promoting translation
Littler believes that individual governments need to be made more aware not only of the potential health benefits of regenerative medicines, but also of the economic returns. At the same time, it is important not to over-promise and to be realistic about time frames.
The View from the European pharmaceutical industry
Magda Chlebus, Director Science Policy, European Federation of Pharmaceutical Industries and Associations
Over the past decade there has been a massive flight of pharmaceutical R&D from Europe to Asia and the US. The factors that prompted this shift now threaten to undermine the investment that member states and the European Union have made in regenerative medicine and cell therapies, Chlebus said.
To start with, there is a lack of consistency in EU policies. Then there is over-regulation. “The EU generates an enormous number of laws that impact the research environment, and scientists don’t react until it is too late,” said Chlebus.
This is compounded by over-use of the precautionary principle and by a lack of communication and education about human embryonic stem cells and their potential. “People need to understand there are certain things you can’t do without human embryonic stem cells,” Chlebus said. “We need to make clear what Europe would be missing out on.”
The View from big pharma
Theo Meert, Senior Director External Innovation in Neurosciences, Janssen Pharmaceutica
Pharmaceutical companies will only invest in regenerative medicine and cell therapy if there is a supportive ecosystem. This includes appropriate and consistent legislation, regulation and product definitions.
It also requires a body of publicly-funded research that is open for industry to draw on. If academics cannot get funding for human embryonic stem cell research in Horizon 2020, a gap will open up in European expertise, Meert believes.
Clinical development will require the cooperation of patients, and it is critical to ensure there is an appropriate system of informed consent.
In addition, there must to be an accredited quality control system in place to guarantee consistency in cell therapy products. The basic research needed to underpin this system is pre-competitive, and could be carried out in publicly-funded centres that bring academics, clinicians and industry together, Meert said.