Real-life impacts of olipudase alfa: experiences of adults receiving enzyme replacement therapy for acid sphingomyelinase deficiency-results from an international survey study.

Background: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder caused by SMPD1 mutations, resulting in sphingomyelin accumulation and diverse manifestations. Olipudase alfa, an enzyme replacement therapy, has shown efficacy in treating non-neurological symptoms of ASMD, while its impact on patient-reported outcomes remains underexplored. Therefore, there is a need to investigate the disease burden, patient perspectives, treatment expectations, risk tolerance, and unmet needs of adult ASMD patients receiving olipudase alfa.

Methods: A retrospective case series design was employed, incorporating online surveys and semi-structured interviews. Surveys explored demographics, symptoms, and treatment experiences, drawing on input from stakeholders, including researchers, clinicians, and patient advocacy groups. Participants aged 18 or older with a confirmed ASMD diagnosis and receiving olipudase alfa were recruited through patient organisations. Surveys were administered online via Qualtrics, and interviews were conducted and transcribed for qualitative analysis.

Results: ASMD posed substantial burden on participants' ability to perform daily activities. Olipudase alfa was associated with substantial improvement in non-neurological manifestations of ASMD. Participants perceived the drug's risks to be low, and the benefits outweigh the risks or burden. Most participants express satisfaction with olipudase alfa and their ability to lead better lives due to fewer ASMD symptoms since starting treatment.

Conclusions: This study highlights the burden of ASMD and the positive impact of olipudase alfa on patients' quality of life. Findings reinforce the importance of early diagnosis and accessible treatment. Despite the favourable outcomes, there remains a need for therapies targeting neurological manifestations and reducing treatment burden. Future research should focus on long-term outcomes and continue to prioritise patient-reported experiences to guide therapeutic development.