Navigating patient access pathways for non-viral RNA-based therapeutics: a comparative review of health technology assessment and reimbursement pathways across six countries.

Abstract

RNA therapies are transforming the treatment landscape for several rare, severe, and previously untreatable diseases. Regulatory approval only permits the medicine to be marketed; it does not determine whether a public health system will fund it. In Europe, this typically relies on national reimbursement bodies, following a Health Technology Assessment (HTA) or comparable processes. Despite the clinical promise of RNA therapeutics, they pose a significant challenge for funding decision makers due to their high costs, limited evidence on long-term effectiveness, and often narrow indications. Therefore, this targeted comparative review was conducted to analyse national HTA decisions and reimbursement policies for selected non-viral RNA therapeutics across six countries: Ireland, England, France, Germany, Canada, and the United States. HTA agencies across the reviewed countries generally issued favourable recommendations for RNA therapeutics reimbursement despite different assessment criteria, citing clinical effectiveness, unmet need, and budget impact as central factors. However, HTA agencies also expressed concerns about long-term benefit, meeting cost-effectiveness thresholds, and limited real-world evidence of these therapeutics. RNA therapeutics were often reimbursed under conditional reimbursement schemes or managed entry pathways. Countries with formal orphan drug pathways or flexible reimbursement mechanisms (e.g. Germany, England) were more likely to facilitate earlier access. With the accelerating growth in new RNA therapeutics, there needs to be consideration of the capacity for, and appropriateness of, current approaches of assessment and reimbursement, as well as the extent to which harmonisation of methods can support equitable and evidence-based access to patients across Europe.