The cost of teriflunomide in the treatment of relapsing-remitting multiple sclerosis

Teriflunomide, used globally to treat multiple sclerosis (MS) and widely subsidised for this indication including in Australia and New Zealand, is the main metabolite of leflunomide, an older immune-modulating drug. Leflunomide therefore represents a potential alternative therapy for MS. Teriflunomide is about 50-500 times more expensive than leflunomide, depending on prices in each jurisdiction. I wished to study how this situation arose.

Web search to obtain the publicly available minutes of eight international regulatory bodies that have approved teriflunomide for the governments of the US, Canada, Europe, England, Scotland, Australia (TGA and PBS) and New Zealand, and examination of the processes and minuted discussions concerning the metabolic, efficacy, toxicity and cost relationship between teriflunomide and leflunomide.

The relationship between the two drugs and their relative efficacy or toxicity in MS was considered by three of eight agencies (Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Canadian Agency for Drugs and Technology in Health (CADTH)). The remaining agencies accepted teriflunomide applications at face value, assessed cost-effectiveness against contemporaneous drugs used for treating MS, and did not discuss the potential role of leflunomide as a therapy for MS. No agency minuted the implications of the cost difference.

Efficacy for leflunomide in MS is likely but unproven. The sponsor presented a case for teriflunomide that was within the established procedures for drug agencies in establishing cost-effectiveness, and agencies did not stray from their normal procedures. As a result, an opportunity to decrease the cost of treating MS has been missed. Though off-label use of leflunomide is possible, this is unlikely without a publicly-funded trial to demonstrate non-inferiority with regard to efficacy and safety.