Rare diseases affect up to 36 million people in the EU, but often no treatment options are available. The ideas and early stages of development of therapies for rare diseases often originate from academic institutions. But further development often stagnates. This may be due to the complexity of the disease, small patient populations, high risks for industry with limited options for reimbursement, regulatory challenges and high costs for society. In the classic pharmaceutical model, the interests of companies, society, academic institutions and the government regularly conflict. This leads to a system failure: innovations for rare diseases such as ATMPs and/or gene-based therapies, including RNA therapies (ATMP+), and drug repurposing do not optimally progress in development. Either the final price is beyond our willingness to pay or there is no suitable, predictable business case.