ABSTRACT
High unmet medical needs have been important contributors to the accelerated approval of these transformative RMs based on limited evidence indicating short-term benefits outweigh possible risks. However, the substantial uncertainties in the comparative effectiveness and durability of clinical benefits constituted the biggest challenge for the HTA of RM. Furthermore, limitations in clinical evidence undermine the robustness of the economic analysis, which must rely on intensive extrapolations and assumptions on the long-term outcomes. The high prices of RMs raised controversies regarding whether such prices are justified in relation to the manufacturing cost and clinical benefits. Payers will face a financial crisis to cover upcoming RMs targeting not only rare diseases but also more prevalent diseases. Outcome-based agreements are increasingly used for RMs, while there are practical and legislative hurdles to overcome to allow the broader use of these agreements. The successful market access of ATMPs could not be accomplished by one sole party; instead, it required intensive engagements of all relevant stakeholders across different agencies and even across countries. Moreover, the collaborations of different players with complementary capacities will be the key to expedite the transition from scientific discovery to the ultimate commercialization.
