Analysis Explores Gene Therapy’s Potential to Be Cost-Effective in SCD

Gene therapy to treat sickle cell disease (SCD) is a highly promising potential solution for the blood disorder, but only if its cost does not exceed $2 million, according to new research published today in Annals of Internal Medicine.¹

This new modeling analysis examines the cost-effectiveness of gene therapy to treat SCD in the United States among a primarily African heritage population, which accounts for over 80% of patients who have the blood disorder, note the analysis’ authors. Their assumed price was $2 million, which echoes Institute for Clinical and Economic Review data from last year showing exagamglogene autotemcel (exa-cel [Casgevy]; Vertex Pharmaceuticals) and lovotibeglogene autotemcel (lovo-cel [Lyfgenia]; bluebird bio) to be cost-effective if priced between $1.35 million and $2.05 million.² In December, the FDA approved exa-cel and lovo-cel to treat SCD,³—making them the first gene therapies approved to treat this often-debilitating blood disorder—but their 7-figure prices per infusion exceed this range: $2.2 million and $3.1 million, respectively.⁴

The outcome of concern was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) from health care sector and societal perspectives among 3 groups of individuals:

• Medicaid enrollees aged 0 to 100 years
• Medicare fee-for-service enrollees aged 18 to 100 years, including those with disability-related coverage who were younger than 65 years
• Dual-eligible enrollees aged 0 to 100 years

Anirban Basu, PhD, MS | Image Credit: University of Washington School of Pharmacy

When asked how they decided on the $2 million price, lead investigator Anirban Basu, PhD, MS, the Stergachis Family Endowed Director and Professor of Health Economics at the University of Washington School of Pharmacy, said in an interview with The American Journal of Managed Care^®, “This was about the median prices of all gene therapies in the market; this paper demonstrates the range of gene therapy prices on the market.”

Additional research shows that the top prices per dose for FDA-approved gene therapies in the United States range from $2.1 million for onasemnogene abeparvovec (Zolgensma, Novartis), which treats spinal muscular atrophy, to $3.5 million for etranacogene dezaparvovec (Hemgenix, CSL Behring), which treats hemophilia B.^5,6

For the present analysis, which estimates gene therapy’s cost-effectiveness only among those who have SCD and are eligible for the treatment vs those who received common care—approximately 10% to 20% of the overall population living with SCD, according to Basu—the investigators used the University of Washington Model for Economic Analysis of Sickle Cell Cure (UW-MEASURE) and the Fred Hutchinson Institute Sickle Cell Disease Outcomes Research and Economics Model (FH-HISCORE) models. These simulation models were independently developed by 2 research groups through the Cure Sickle Cell Initiative, from the National Heart, Lung, and Blood Institute, to have SCD-related costs and outcomes from different care modalities. Data fed into the models comprised price, administration, efficacy, and adverse effects related to gene therapy treatment; health state utility (or health-related quality of life); direct medical costs; time use and productivity; and effects on caregivers and family members.

“UW-MEASURE is a microsimulation model that propagates each individual at a time through the model to simulate their trajectory of lifetime outcomes,” Basu explained, “and FH-HISCORE propagates a cohort of individuals together as a group through the model to do the same.”

For life expectancy and QALYs under the UW-MEASURE model, a person with SCD who receives gene therapy has potential for an additional undiscounted 17.4 years of life, and under FH-HISCORE, 17 years. Discounted QALYs, or future QALYs discounted to present value to reflect receipt of care now,⁷ were 9.8 years overall and 11.9 years when including family benefits under UW-MEASURE and 5.1 and 5.4 years, respectively, under FH-HISCORE.

UW-MEASURE also considered health years in total (HYT), and those came out to be 17.6 discounted HYTs overall and 19.7 when including family benefits.

Overall incremental health care costs, including the price of a gene therapy and administrative costs were an estimated at $2,298,780 under UW-MEASURE and $2,178,228 under FH-HISCORE. Corresponding lifetime societal costs were $1,498,971 and $1,568,094. Assuming the investigators’ gene therapy price tag of $2 million:

• Under UW-MEASURE, the ICERs would be $193,000/QALY and $117,000/HYT from the health care sector perspective and $126,000/QALY and $76,000/HYT from the societal perspective
• Under FH-HISCORE, the ICERs would be $427,000/QALY from the health care sector perspective and $281,000/QALY from the societal perspective
• Under UW-MEASURE, the value-based price for gene therapy ranged from $1.7 million to $2.0 million at QALY thresholds of $100,000/QALY or $75,000/HYT, and $2.3 million to $2.7 million if equity-informed thresholds were used

“Accounting for uncertainty, we found a high (> 95%) probability of acceptability for a gene therapy price of $2 million when using equity-informed thresholds,” the study authors wrote. “The confidence level of acceptability declined above an acquisition cost of $2.5 million.”

When asked why these findings are so important for both the SCD community and advancement of gene therapy, Basu replied, “Typical life expectancy for people with SCD is about 20 to 30 years shorter than the general population and is marred with low quality of life. Gene therapies show great promise in bringing a widely applicable curative approach to SCDs, an area characterized by high disease burden, and understanding the value and the prices at which these innovative therapies are cost-effective is important for society. Our analyses provide detailed early evidence of such therapies' potential value and value-based prices, and showcases a comprehensive approach to valuing innovative therapies.”

He added that these findings could have implications beyond the SCD space in that a sizeable patient population who does not have SCD could be eligible for future gene therapies and enrolled in Medicare, Medicaid, or both. If the current price estimates of gene therapy for the relatively small gene therapy–eligible SCD population—according to his estimates, this population is between 5000 and 10,000—carry concerns about the consequences for budget impact, "we should be even more worried about what's to come," Basu notes.

References

1. Basu A, Winn AN, Johnson KM, et al. Gene therapy versus common care for eligible individuals with sickle cell disease in the United States. Ann Intern Med. Published online January 22, 2024. doi:10.7326/M23-1520
2. Sickle cell disease: an assessment of two gene therapies: exagamglogene autotemcel and lovotibeglogene autotemcel. ICER. July 27, 2023. Accessed January 18, 2024. http://tinyurl.com/yckfh84m
3. FDA approves first gene therapies to treat patients with sickle cell disease. News release. FDA. December 8, 2023. Accessed January 18, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
4. Davies K. FDA approves Casgevy, the first CRISPR therapy, for sickle cell disease. Genetic Engineering & Biotechnology News. December 8, 2023. Accessed January 22, 2024. https://www.genengnews.com/topics/genome-editing/fda-approves-casgevy-the-first-crispr-therapy-for-sickle-cell-disease/
5. The top 5 most expensive FDA-approved gene therapies. Lifesciences Intelligence. May 24, 2023. Accessed January 18, 2024. https://lifesciencesintelligence.com/features/the-top-5-most-expensive-fda-approved-gene-therapies
6. Cohen J. Despite eye-popping $3.5 million price tag for gene therapy Hemgenix, budget impact for most payers will be relatively small. Forbes. December 2, 2022. Accessed January 18, 2024. http://tinyurl.com/ysejjjbh
7. Whitehead SJ, Ali S. Health outcomes in economic evaluation: the QALY and utilities. Br Med Bull. 2010:96:5-21. doi:10.1093/bmb/ldq033