OBJECTIVES: Gene therapies (GTx) show high potential in many rare diseases, often in treating patients with the highest unmet medical need. Since 2012, 12 single-administration non-oncological GTx have been approved in the US and Europe, and the number of new therapies is expected to increase (58 ongoing phase 3 clinical trials listed on clinicaltrials.gov with expected completion in the next 5 years). This research aimed to investigate risk-sharing agreements (RSA) used to manage GTx costs and increase patient access.

METHODS: We conducted a targeted search to identify publicly available information on implemented RSAs for non-oncological single-administration GTx in UK, Canada, Australia, and the US.

RESULTS: The available information on RSAs for GTx is limited and varies across the countries. Out of 9 funded single-administration GTx (eladocagene exuparvovec, etranacogene dezaparvovec, betibeglogene autotemcel, valoctocogene roxaparvovec, voretigene neparvovec, exagamglogene autotemcel, lovotibeglogene autotemcel, atidarsagene autotemcel, onasemnogene abeparvovec), RSAs were identified in the US (n=7), UK (n=5), Canada (n=3), and Australia (n=2). These included financial-based (n=11), performance-based (n=9) and mixed (n=1) schemes. Price discounts were used in Canada and UK. Performance-based RSAs were used in Australia and the US linked to reduced mortality or improved clinically relevant outcomes (e.g., motor milestones for onasemnogene abeparvovec). The time horizon for the outcomes assessment varied from 60 days (voretigene neparvovec) to 5 years (onasemnogene abeparvovec). In case of treatment failure, RSAs include provisions for additional rebates or payback.

CONCLUSIONS: To manage uncertainties around long-term benefits and financial impact, local decision-makers implement RSAs. Canada and UK mainly use financial-based schemes built on simple price discounts. Australia and the US aim at implementing schemes whereby treatment cost payers incur corresponds to expected health outcome for a particular patient.