PDB40 An EARLY Cost-Utility MODEL of Mrna-Based Therapies Compared with Standard of Care in EARLY-Onset Methylmalonic Acidaemia in the United Kingdom

Abstract

Methylmalonic acidaemia (MMA) is a rare metabolic disease with high mortality rates and severe chronic sequelae in children surviving the initial disease onset. Current standard of care (SOC) includes low-protein diet, pharmacologic therapy and, potentially, liver transplantation or combined liver-kidney transplantation. Also, innovative intracellular mRNA-based therapies are currently being trialled that could offer novel systemic treatment. 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 in early-onset MMA in the United Kingdom (UK). A Markov model simulating a hypothetical cohort of newborn MMA 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 with diet-based management, the variables with the largest impact on the ICER were the annual cost of mRNA-based therapy, improvement in utility following mRNA-based therapy, patient weight, cost of medical foods and cost of L-carnitine 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 MMA and guide the design of evidence generation activities.