PDB24 An EARLY Cost-Utility MODEL of Mrna-Based Therapies Compared with Standard of Care in EARLY-Onset Propionic Acidaemia in the United Kingdom

Abstract

Propionic acidaemia (PA) is a rare metabolic disease with high mortality rates and severe chronic sequelae in children surviving the initial onset of the disease. Current standard of care (SOC) includes low-protein diet, pharmacologic therapy and, potentially, liver transplantation. Also, innovative intracellular mRNA-based therapies are currently being trialled. The objective of this study was to build an early cost-utility model to identify key variables impacting the cost-utility of mRNA-based therapies versus SOC (diet or diet/transplant) in early-onset PA in the United Kingdom (UK). A Markov model simulating a hypothetical cohort of newborn PA patients was developed from the UK healthcare system perspective. Efficacy and cost inputs were obtained from the literature, British National Formulary and NHS Reference Costs. Quality-adjusted life years (QALYs) and costs were estimated for each treatment arm over a lifetime horizon, with a discount rate of 3.5% for both. One- and two-way sensitivity analyses were conducted to identify key model drivers, such as those with largest impact on the incremental cost-effectiveness ratio (ICER). When comparing mRNA-based therapies versus patients receiving diet only, the variables with the largest impact on ICER were patient weight, the annual cost of mRNA-based therapy, cost of medical foods, cost of L-carnitine and improvement in utility following mRNA-based therapy in that order. Results were similar when comparing mRNA-based therapies with the diet/transplant arm. Despite the current lack of a strong evidence base, this model can be used to estimate value-based prices of mRNA-based therapies in PA and guide the design of evidence generation activities.