PRO10 Identifying Appropriate PROXY Diseases for Estimating LONG-TERM Survival and IMPACT on Health-Related Quality of Life of Patients with Aromatic L-Amino Acid Decarboxylase Deficiency (AADC-D)

Abstract

We aimed to identify diseases similar in characteristics to AADC deficiency (AADC-d) that can provide proxy estimates for health-related quality of life (HRQoL) and long-term survival of AADC-d patients. These estimates will be used to support the economic model development for eladocagene exuparvovec. A literature search and clinician survey were conducted to identify proxy diseases for AADC-d. The literature was searched for observational studies, single arm clinical trials, randomized clinical trials, systematic reviews, case studies and case reports between January 2015 and January 2020 from clinicaltrials.gov and PubMed.gov. Studies among paediatric patients with motor associated neurological, genetic, or inherited conditions were included. Additionally, a survey was administered electronically to 25 clinicians globally to assess appropriateness of anoxic encephalopathy, paraplegia, tyrosine hydroxylase (TH) deficiency, guanosine triphosphate cyclohydrolase deficiency, sepiapterin reductase deficiency (SR), dopamine transporter deficiency syndrome as proxies. Appropriateness of disease proxy was determined based on similarity in disease characteristics, disease onset, natural history of disease progression, and data availability. Spinal muscular atrophy (SMA), Duchenne muscular dystrophy, metachromatic leukodystrophy, and cerebral palsy (CP) were identified in the literature search as suitable proxies. Survival and HRQoL data were available for SMA type I and CP since motor specific developmental milestones were measured as an endpoint in the related clinical trials. Survey results indicate TH deficiency and SR deficiency could be suitable proxies, but a lack of published data on survival and HRQoL limit their use for economic modeling in AADC-d. CP was preferred by clinicians as an appropriate proxy in AADC-d, in the absence of required data for other proxies. This study provides evidence to fill a gap in the literature for AADC-d patients’ outcomes. The available mortality and HRQoL data for the proxy diseases may be used to estimate the long-term outcomes for patients with AADC-d.