ATMPs (Advanced Therapy Medicinal Products) are complex drugs based on cells, genes or tissues. Currently, they are mainly developed and used to treat certain cancers or genetic disorders. Only a small number of ATMPs are currently commercialised by the industry and they are often very expensive, up to several million euros per treatment. At the request of several Belgian cancer associations, the Federal Health Care Knowledge Centre (KCE) looked into ways of optimising the role of Belgian universities in this field, in order to improve access to these drugs for patients. This requires in-depth expertise from both governments and academics, as well as closer cooperation. Moreover, as the development of ATMPs can take many years, funding should also cover a sufficiently long period and be less fragmented.
ATMPs are complex drugs based on cells, genes and tissues which are used, among other things, to treat cancer or genetic disorders. It is a promising field, which could one day yield treatments for a whole range of other, currently incurable diseases. The first stages of research around ATMPs are often carried out by universities, while the later stages of development, market authorisation application and commercialisation are mainly handled by industry.
Limited access for patients
A little over five years ago, everyone in Belgium discovered the story of baby Pia , who suffers from a rare genetic disease affecting her muscles. A potentially life-saving gene therapy (Novartis’ Zolgensma®) was available but extremely expensive (€1.9 million), and not reimbursed by the mandatory health insurance at the time. Ultimately, a crowdfunding organised by Pia’s parents succeeded in collecting the necessary funds. Today, Zolgensma® is reimbursed in Belgium for children under the age of 2.
Innovative treatments such as Zolgensma® attracted considerable attention at the time, but other ATMPs, such as CAR-T cancer therapies, face the same challenges: extremely high prices, complex technologies, mostly small patient populations and considerable difficulties in generating sufficient clinical evidence, especially about long-term effects.
Some ATMPs have so little commercial potential that the pharmaceutical industry is simply not willing to invest in them. Nevertheless, even when an ATMP initially attracts a company’s interest, it may later be withdrawn from the market, most often for similar reason . This happened to 7 of the 27 ATMPs with a EU market authorisation. In Belgium, less than half of the EU-authorised ATMPs are available, and they are all reimbursed through confidential agreements (which means the price negotiated between the company and the health insurance institute is not made public).
Academic development on the rise
KCE explored how academic institutions can play a greater role in developing ATMPs and in making them available to patients through clinical trials, specific hospital compounds (hospital exemption) or a more “conventional” marketing process. For inspiration, Belgium could look to The Netherlands and Spain, where academic teams have developed products which they are currently in the process of bringing to the market. Recently, an Italian non-profit foundation also decided to take over the commercialisation of an ATMP that had been abandoned by the industry.
Few academic clinical trials in Belgium
Many clinical trials with ATMPs are ongoing in Belgium, but only a small number are initiated by academic institutions themselves. Most of them receive funding from the EU, the Belgian federated entities or non-profit organisations (e.g. Kom op tegen Kanker in Flanders or Fondation contre le Cancer/Stichting tegen Kanker).
A hospital exemption allows a developer to deliver its ATMP to individual patients in a hospital, under strict conditions, without having to go through the complex EU marketing authorisation procedure. However, this option, introduced in Belgium in 2017, has met with little interest : only one such exemption was granted by the Federal Agency for Medicines and Health Products, to a commercial spin-off. This could be explained partly by the fact Universities and the Agency have a different interpretation of the conditions for hospital exemption, with academics believing these are almost impossible to fulfil.
Fragmented responsibilities and funding
Based on a study of scientific literature, foreign examples, and interviews with Belgian stakeholders, KCE pinpointed a number of barriers that currently delay or even prevent the development of more academic ATMPs.
The required expertise seems very fragmented, as are the political responsibilities and the main motivations for funding. For instance, public funding through the federated entities mainly aims at boosting the economy, employment and research, and does not structurally take into account public health needs.
Conditions for efficient support of academic ATMPs
KCE also suggested a number of solutions to better support the academic development of ATMPs in Belgium.
There is a clear need for sufficient, stable and less fragmented financial resources over a sufficiently long period. These can be allocated by the federal government and the federated entities, provided they set joint priorities, carefully check feasibility and make sure not to violate EU state aid rules.
If the project involves a partnership with an industrial player, it may be advisable to request guarantees that the results of publicly funded research will remain available and affordable for society.
Regarding the rules on hospital exemptions, which are currently under review at EU level, KCE advocates more harmonisation between member states, which currently each set their own conditions. For Belgium, KCE recommends that the Federal Agency for Medicines and Health Products publish the interpretations of the conditions on its website and actively encourage universities to make use of the possibility of an informal consultation before they submit their applications.
Besides funding, there is also a need for more pooled and accessible translational expertise both within government bodies and within universities, and a need for more collaboration.
