OBJECTIVES : To characterize the economic differences of Advanced Therapy Medicinal Products (ATMP) therapies versus chronic therapies using the ultra-rare neuropediatric disease Aromatic l-amino acid decarboxylase-deficiency (AADC-d) as an example.

METHODS : Based on a structured literature search performed 5/2020 to 6/2021 relevant literature and statements were identified in Medline, Google, key congresses, and grey literature. Key differences of ATMPs for ultra-rare diseases were analyzed both from healthcare-system and manufacturer perspectives. The example of somatic gene therapy with eladocagene exuparvovec as a potential one-time-treatment for AADC-d is characterized with key clinical data.

RESULTS : From an healthcare-system perspective, 9 key differentiating characteristics for ATMPs in ultra-rare diseases were identified, including high nominal price levels, short-term budgetary concerns, uncertainty of patient numbers whilst facing long term evidence limitation and real-world applicability, confirmation of clinical benefit, extent of profit, multiple and highly specialized treatment center requirements, separate and specific regulatory processes, especially regarding quality and risk management materials as well as general risks of any genetic treatments. From manufacturer perspective, a second 9–point- list of specific relevance to ensure ATMP success was defined including product and market-specific aspects as well as patients’ access to therapy. The example of somatic gene therapy with eladocagene exuparvovec in AADC-d provides 5-year data showing a dramatic effect according to German Institute for Quality and Efficiency in Health Care (IQWiG)-definition regarding the motoric endpoint “head control”. The motoric summary scale values (PDMS-2) increase over time in most patients. Especially regarding gene therapies, a 5-year period represents extended follow-up.

CONCLUSIONS : Clinical efficacy, especially of long-term efficacy and safety, are key drivers of achieving value for both, from a healthcare-system´s lens as well as for manufacturers. In addition, the burden of disease for patients and caregivers is fundamental as in the example of the neuropediatric disease AADC-d.