OBJECTIVES: To determine the impact in Portugal of patient weight dosing with MAVENCLAD^®, a novel medicine approved in the EU for the treatment of patients with highly active relapsing multiple sclerosis, when compared with non-weight dependent alternative medicines, such as natalizumab and fingolimod. METHODS: An Excel patient-level simulation model was developed to determine time on treatment for a population of high disease activity patients, using time to first relapse found in published literature as a proxy for time on treatment. Costs of treatment with MAVENCLAD^® were determined taking into consideration the Portuguese population weight distribution, with an entry selection of Female/Male of 2:1. Cost of therapy for each sampled individual was compared with the cost of the alternative treatments for the same time period. Model was run for 10.000 patients, for three time horizons (4, 5 and 6 years). Costs were obtained from Portuguese data sources. RESULTS: In a total of 10.000 Monte Carlo simulations it was found that the average weight and treatment posology for MAVENCLAD^® in the Portuguese population tends to be higher than the one used by national authorities in their assessment (12,25 vs 13,11 tablets per patient), however on average MAVENCLAD^® remains cost-saving in all average comparisons. When compared with fingolimod, MAVENCLAD^® results on average savings per patient of 10.624,54 €, 23.636,92 € and 34.806,79 € when using respectively 4, 5 and 6 years as time horizons. Regarding natalizumab, MAVENCLAD^® generated net savings per patient of 2.392,86 €, 13.693,27 € and 23.393,17 € over the same time periods. CONCLUSIONS: Patient weight distribution of the Portuguese population leads to higher costs with MAVENCLAD^® than initially anticipated, however in all time horizons used MAVENCLAD^® remains a cost-saving alternative when compared with both fingolimod and natalizumab, for the treatment of patients with high disease activity relapsing multiple sclerosis.