Introduction: Luxturna is the first gene therapy approved for the treatment of rare disease inherited retinal dystrophy (IRD) with confirmed biallelic RPE65 mutation. The disease impacts patients at a young age and eventually causes blindness. Luxturna has been recommended for treatment by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA). Still, the Danish Medicines Council could not recommend the drug for these patients due to the findings from the cost analysis. The medication was too costly, and the long-term effects of Luxturna on the patients were unknown. We decided to conduct a full economic evaluation, specifically a cost-utility analysis (CUA), to determine if Luxturna was cost-effective compared to the current standard of care (SoC) treatment.
Methods: A cost-utility analysis (CUA) is done using a decision analytic model. A Markov model was created by using relevant costs and effects to estimate the incremental cost per QALY (quality-adjusted-life-year) gained from Luxturna compared with the SoC treatment from a Danish narrow societal perspective with the inclusion of productivity costs. The cost and effect data were estimated based on the assumption of a patient's lifetime, starting at 15 to death. The Markov Model data was obtained from phase III clinical trials and a U.K. Economic Evaluation on Luxturna by Viriato et al., which is based on a natural history study on RPE65-mediated IRD. The health states definitions were based on the American Medical Association Guides, and utility scores were based on Lloyd et al. 2019 study, which estimated IRD patients' utilities. The costs were estimated based on the cost analysis of Luxturna conducted by the Danish Medicines Council and AMGROS. The indirect costs were estimated using values from Denmark Statistics to calculate productivity loss.
Results: The base case incremental cost-effectiveness ratio (ICER) was 521,990.97 DKK/quality-adjusted life-year (QALY).
The deterministic sensitivity analysis results showed that the ICER was more sensitive to time horizon, discount rate, the exclusion of productivity loss, and the different assumptions of long-term treatment effect.
Probabilistic sensitivity analysis (PSA) showed Luxturna was a 25.9% chance of being cost-effective if the willingness-to-pay (WTP) threshold was set to be 325,000 DKK/QALY, and 77.9% chance of being cost-effective at 745,000 DKK/QALY.
Conclusion: Luxturna is likely to be cost-effective if the WTP threshold is 745,000 DKK/QALY (based on Swedish experience for rare diseases). Luxturna is not cost-effective if the WTP threshold is set to be 325,000 DKK/QALY (often-cited Danish WTP threshold, although there is no official threshold in Denmark).
There should be further investigation on the threshold for orphan drugs in Denmark for a decision rule.