Cost-effectiveness of a hypothetical cell or gene therapy cure for sickle cell disease

Abstract

Sickle cell disease (SCD) is a group of inherited genetic conditions associated with lifelong complications and increased healthcare resource utilization. Standard treatment for SCD in the US varies based on stage of the disease and observed clinical severity. In this study, we aim to evaluate the potential cost-effectiveness of a durable cell or gene therapy cure for sickle cell disease from the US healthcare sector perspective. We developed a lifetime Markov model to evaluate the cost-effectiveness of a hypothetical single-administration durable treatment (DT) for SCD provided at birth, relative to standard of care (SOC). We informed model inputs including direct healthcare costs, health state utility weights, transition probabilities, and mortality rates using a retrospective database analysis of commercially insured individuals and the medical literature. Our primary outcome of interest was the incremental cost-effectiveness ratio (ICER) of DT versus SOC evaluated at a base case willingness-to-pay (WTP) threshold of $150,000 per quality-adjusted life year (QALY). We tested the robustness of our base case findings through scenario, deterministic sensitivity (DSA), and probabilistic sensitivity analyses (PSA). In the base case analysis, treatment with DT was cost-effective with an ICER of $140,877/QALY relative to SOC for a hypothetical cohort involving 47% females. Both males (ICER of $135,574/QALY) and females (ICER of $146,511/QALY) were similarly cost-effective to treat. In univariate DSA the base case ICER was most sensitive to the costs of treating males, DT treatment cost, and the discount rate. In PSA, DT was cost-effective in 32.7%, 66.0%, and 92.6% of 10,000 simulations at WTP values of $100,000, $150,000, and $200,000 per QALY, respectively. A scenario analysis showed cost-effectiveness of DT is highly contingent on assumed lifetime durability of the cure. A hypothetical cell or gene therapy cure for SCD is likely to be cost-effective from the US healthcare sector perspective. Large upfront costs of a single administration cure are offset by significant downstream gains in health for patients treated early in life. We find cost-effectiveness outcomes do not vary substantially by gender; however, several model parameters including assumed durability and upfront cost of DT are likely to influence cost-effectiveness findings.

Development of a conceptual model for evaluating new non-curative and curative therapies for sickle cell disease

“…The remaining six models were trial-based, life-table models, or only considered treatment complications [ 18 , 20 , 44 – 47 ]. Stroke and vaso-occlusive events were both included in the structure of four models [ 19 , 48 – 51 ], acute chest syndrome was included in three models [ 48 – 50 ], and splenic sequestration was included in two models [ 19 , 50 ]. Bradt et al developed the only model with additional disease attributes [ 49 ].…”

“…We have developed the first conceptual model for evaluating specific curative therapies for SCD. A previous modeling study assessed the value of a hypothetical curative therapy for patients with SCD that is administered at birth and completely eliminates all disease-related complications [ 51 ]. The authors developed a Markov model with separate health states for mild, moderate, and severe SCD based on the frequency of VOE.…”

Are we prepared to deliver gene‐targeted therapies for rare diseases?

“…The results have been spectacular, with rescue of motor neurons and correction of most of the motor symptoms in infants who are diagnosed in infancy and can most benefit from the treatment. However, Zolgensma ® is one of the most expensive drugs on the market, with a cost of $2.1 million per patient dose (Salcedo, Bulovic, & Young, 2021).…”

Debating the Future of Sickle Cell Disease Curative Therapy: Haploidentical Hematopoietic Stem Cell Transplantation vs. Gene Therapy

“…Curative therapy is likely to be cost-effective given large upfront costs are offset by significant downstream gains in health for patients treated early in life. In probabilistic sensitivity analysis, durable treatment is cost-effective at a minimum willingness to pay (WTP) of USD 150,000 per quality-adjusted life year (QALY) at single administration costs of USD 2.18 M for a cure duration lasting a lifetime [ 95 ]. Curative therapy generates an average of 26.4 discounted QALYs at a cost of USD 2,372,482 per patient vs. standard of care resulting in 17.9 discounted QALYs at a discounted cost of USD 1,175,566 per patient.…”