Is Gene Therapy Cost-Effective for Hemophilia B?

A study published in Blood found the use of gene therapy for hemophilia B to be more cost-effective than prophylaxis or on-demand treatment with factor supplementation across a patient’s lifespan.

“Gene therapy has the potential to yield significant budget savings for health care systems while improving patients’ outcomes and quality of life,” said lead author Nancy Bolous, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee. “This analysis adds further data to the complex public discourse surrounding drug pricing and extends the conversation beyond preference-based cost-effectiveness analyses.”

Gene therapy – for hemophilia in particular – is currently at a critical point, Dr. Bolous told ASH Clinical News. “Novel technology is undergoing clinical trials and proving success, but third-party payers and insurance companies might still be skeptical about its affordability due to its high upfront cost.” Without appropriate reimbursement mechanisms in place, she added, patients might never experience the benefits of this technology.

In this study, Dr. Bolous and colleagues from St. Jude compared the costs and potential cost-effectiveness of two approaches in patients with severe hemophilia B: on-demand and prophylactic factor IX (FIX) replacement treatments or adeno-associated virus (AAV)–mediated FIX deficiency-Padua gene therapy.

The study used a cost-utility microsimulation Markov model featuring U.S. patients with severe hemophilia B. Published data also were used to inform transition probabilities between health states (“alive,” “alive with joint damage,” and “dead”) and utilities.

In a probabilistic sensitivity analysis using the standard half life (SHL)-FIX treatment approach, the gene therapy was cost-effective in 43%, 75% and 92% of simulations at a willingness-to-pay threshold of $50,000 per quality-adjusted life year (QALY), $100,000 per QALY, and $150,000 per QALY, respectively.

At the assumed gene therapy’s marketed price of $2,000,000 in the base-case scenario, the investigators estimated that a pharmaceutical company could produce a return on investment of $859,500,000 if 447 patients were treated. Observed manufacturing, administration, and follow-up costs at five years was $87,198 for the AAV-mediated gene therapy vector, determined by St. Jude’s manufacturing facility and clinical practice.

In 10 of 102 scenarios, gene therapy was not deemed cost-effective by one-way sensitivity analyses, compared with alternative treatments. “Patients can find themselves in one or more of these scenarios and become empowered to better understand the pricing and medication authorization decisions by pharma and payers,” said Dr. Bolous.

Gene therapy was cost-effective in a hypothetical case that estimated a discounted factor concentrate price of 20% of the U.S.-based wholesale acquisition cost. According to a probabilistic sensitivity analysis, gene therapy was estimated to be cost-effective in 92% of the simulations when considering a threshold of $150,000 per QALY.

Dr. Bolous explained that the inclusion of manufacturing costs for gene therapy based on clinical trial Current Good Manufacturing Practice (CGMP) production versus only costs reported by commercial entities “make this study unique and can help different stakeholders make more informed decisions.”

This study was limited by the rarity of hemophilia B, which led the investigators to rely on other select data from the overall hemophilia population. Despite this limitation, Dr. Bolous noted that the analytical approach used in this study is relatively generalizable to analyses of other diseases that are amenable to gene therapy interventions.

Dr. Bolous added that future analyses should consider variability between different vector products, the cost of research and development, and, potentially, capital expenditures. “Overall, a greater transparency and support of evidence-based discussions around price equity and what a life-saving therapy should cost society should be the focus of further questions,” she concluded.

The authors report no relevant conflicts of interest.


Bolous NS, Chen Y, Wang H, et al. The cost-effectiveness of gene therapy for severe hemophilia B: Microsimulation study from the United States perspective [published online ahead of print, 2021 Apr 25]. Blood. doi: 10.1182/blood.2021010864.