Reflections from Boston on the future of ATMPs and Regenerative Medicine

During a recent trade mission to Boston, I formulated a key challenge: if we really want to get advanced therapies (ATMPs) to patients – and to do so in a sustainable and affordable way – we need to think disruptively about development, production and valorisation.

The promise and barrier of ATMPs
Advanced Therapy Medicinal Products (ATMPs), such as cell and gene therapies, represent a revolutionary step forward in medicine, and are supported by groundbreaking scientific discoveries, as exemplified by a 2012 Nobel Prize for pioneering stem cell technology. This new class of innovative therapies can bring complete cure (cure instead of care) and often offer the only hope of a cure in (rare) genetic disorders and certain cancers. In Regenerative Medicine, too, we see particularly promising cell-based treatments on the horizon, such as stem cell derived insulin-producing cells for Type I Diabetes. In recent years, we have seen a surge in approvals by regulatory authorities such as the FDA and EMA, and the pipeline is filling up.

But this medical promise comes with hefty barriers. The path from discovery to approved product takes about 10-15 years. This has implications such as the short time of patent protection remaining, while development and production costs are high and the number of patients per therapy is usually limited. This makes it difficult to find an economically attractive model, at least if you want to maintain existing models. Autologous therapies in particular (where the product is made specifically for one patient) are costly and difficult to scale. Even allogeneic (more universal) therapies often do not achieve large volumes given the often orphan indications and the high price.

For large pharmaceutical companies, this is less attractive, and it also remains a tricky story for investors. Many promises have been made in the past, but breakthroughs have so far been limited and profitability remains unconvincing. The result is (too) little investment, and further sky-high prices for existing therapies – sometimes running into the millions of euros – and limited accessibility, especially in Europe. The old ‘blockbuster’ model, where investments are recouped thanks to a few highly successful drugs, is not excluded but clearly less applicable for many ATMPs.

New pathways, new models
To really bring many ATMPs to patients, we need to think disruptively, ‘the system’ needs to be tweaked. RegMed XB therefore also focuses on developing alternative valorisation pathways, including public-private partnerships, non-profit structures and shared responsibility between public and academic partners. This applies to many innovative ATMPs, with a recent notable example from oncology: the Tumour Infiltrating Lymphocytes (TIL) therapy for invasive metastatic melanoma, developed in the Netherlands by the NKI, has been funded with public funds and donations. This therapy is already reimbursed for a specific group of patients, without classical EMA market authorisation. Further work and thought is now being given to follow-up pathways, with important questions such as who takes responsibility over the quality of the product, who vouches for pharmacovigilance and how we keep it all financially affordable.

Initiatives like these show the need for alternative models for ATMP development. But they are still fragile. Indsually, as long as there is no commercial competition, treatment can continue to take place under the so-called Hospital Exemption Clause, at least in some countries. As soon as a commercial alternative enters the market, but how do you determine that, a full regulatory licensing process still needs to be followed – something academic institutions are usually not equipped to do.

The Netherlands at the wheel
Making a real difference requires not only smart development, but also influence on policy and a bit of reinvention of healthcare. Indeed, how are we going to incorporate such treatments into our existing healthcare systems and reimbursement processes. These questions naturally arise in other European countries as well. RegMed XB therefore builds bridges to other European partners, and also joins European initiatives such as Join4ATMP. This ensures that the Netherlands retains an active voice in shaping regulations and funding models for this new class of therapies. ‘Sitting at the table with us, not on the menu,’ as we sharply put it.

Specifically, the national platform and FAST hub ATMP-NL – in formation – in the Netherlands is working hard to combine forces, knowledge and infrastructure. This is where all stakeholders such as academic centres, knowledge institutions and innovative companies, government and healthcare authorities, as well as foundations and patient associations, come together to lay a solid foundation with vision for the development, production and use of ATMPs in the healthcare landscape of the 21st century. The Netherlands has world-leading expertise and experience in this field – from cell production and quality control to (pre)clinical research – and by strategically coordinating this through ATMP-NL, we are building a future-ready national ecosystem. This platform can then also take initiatives to build bridges to other countries such as Belgium and Luxembourg, as well as leading countries in Europe such as France and Germany, to name a few. The timing for this is better today than tomorrow.

Moving forward together
Finally, I already made an appeal in Boston that I would like to repeat here to all stakeholders of FAST and RegMed XB: stay involved. Provide input, ask critical questions and help think about new routes of development and valorisation. Because only if science, government, industry and healthcare act together with the patient can we make this new class of advanced treatments truly sustainable, affordable and widely accessible.

Frank Luyten is co-initiator and medical science director of RegMed XB, professor emeritus at KU Leuven.