Non-myeloablative haploidentical allogeneic stem cell transplantation was the most cost-effective long-term treatment option for adults with sickle cell disease in a modeling study comparing transplant, gene therapy, and standard care.
The study compared three treatment modalities: standard care, gene therapy, and non-myeloablative haploidentical allogeneic hematopoietic stem cell transplantation, or NMAC-HID allo-HSCT. The transplant approach uses reduced-intensity conditioning and a half-matched donor, which may expand access for patients who lack fully matched donors.
The researchers projected lifetime costs and outcomes for adults with sickle cell disease. In the base-case US analysis, gene therapy produced the highest projected health benefit, at 22.1 quality-adjusted life years, but at a lifetime cost of $2.75 million. NMAC-HID allo-HSCT produced 20.1 quality-adjusted life years at $1.15 million, while standard care produced 14.3 quality-adjusted life years at $1.22 million.
“Gene therapy is an incredible immune innovation, but it comes with an astronomical cost,” said lead author George Goshua, assistant professor of medicine at Yale School of Medicine and Yale Cancer Center, in the press release. “Recent prospective studies suggest that stem cell transplantation is now safer and more efficacious than before for people living with sickle cell disease, but data on its cost-effectiveness, especially in the era of gene therapy, have been limited.”
The model incorporated key adverse events, including graft failure, transplant-related mortality, and graft-versus-host disease. On that basis, the authors estimated that the US threshold price for gene therapy would be $627,000 or $740,000, depending on the transplant dataset used – a 66 to 71 percent reduction from current gene therapy pricing. Using standard care as the comparator, the US threshold price for gene therapy was $1.4 million.
“No matter how much we adjusted from base case assumptions or accounted for uncertainty, NMAC-HID allo-HSCT delivered the best clinical value for cost,” Goshua said.
The authors also extended the analysis to India, Nigeria, and Tanzania, where cost-effective price thresholds for gene therapy were far lower than in the US. Against NMAC-HID allo-HSCT, estimated gene therapy thresholds ranged from $24,000 to $35,000 at supply-side cost-effectiveness thresholds, reflecting the different health-system economics and resource constraints in those settings.
Goshua cautioned that cost-effectiveness data should inform policy decisions, not limit patient choice. “Gene therapy may be the best option for many patients, and these data should not be interpreted as reason to deny them coverage,” he said. “Treating physicians must continue to discuss all options with patients in the context of shared patient-physician decision making.”
The analysis has several limitations. Long-term safety and efficacy data for both gene therapy and NMAC-HID allo-HSCT remain limited, and the model lacked patient-level data across trials. It also assumed that patients pursuing curative treatment had a viable donor and no prohibitive donor-specific antibodies, did not explicitly include fertility preservation costs, and relied on public gene therapy list prices rather than confidential payer-negotiated prices.
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