The estimated annual financial impact of gene therapy in the United States

Acknowledgements

We thank Sarah Antiles and Nora Yang for assisting with the preparation of the data. We also thank Jon Campbell, Charles Gerrits, Kathy Gooch, Stacey Kowal, Donald Nichols, Mark Trusheim, Karen Tsai, and Ed Tuttle for helpful comments, and Gabriela Gracia and Jayna Cummings for editorial support. The views and opinions expressed in this article are those of the authors only and do not necessarily represent the views and opinions of any other organizations, any of their affiliates or employees, or any of the individuals acknowledged above. Funding support from the MIT Laboratory for Financial Engineering is gratefully acknowledged, but no direct funding was received for this study and no funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of this manuscript. The authors were personally salaried by their institutions during the period of writing (though no specific salary was set aside or given for the writing of this manuscript). More detailed conflict of interest disclosures are provided after the Conclusion section of the main text. Funding: RMC’s research is funded by grants from the American Cancer Society, the National Cancer Institute, the Leukemia & Lymphoma Society and Arnold Ventures. None of these granting agencies funded her efforts in this work. RMC was also a special economic consultant to the US Food and Drug Administration’s Office of Generic Drugs and is currently a voting committee member of ICER. None of these organizations had any role in the completion of this project, nor RMC’s effort on this project. AL’s research is funded by the MIT Laboratory for Financial Engineering, as well as grants from the Rockefeller Foundation and the Schmidt Futures Foundation. None of these organizations had any role in the completion of this project, nor AL’s effort on this project.

Author contributions

All authors participated in the planning of analyses, interpretation of results and drafting of the manuscript. All authors gave final approval of the manuscript for publication. AL, CW, JG and RMC are responsible for the original conception of the study and its execution. CW, NW, DL performed analyses presented in the manuscript under the supervision of AL, RMC and JG.

Data availability

The data used in this study are available by request from the authors.

Competing interests

CW, DL, and NW report no conflicts. RMC has no conflicts of interest to declare. JG reports no conflicts. JG is a consultant for both the insurer Aetna, Inc. and for the biotech company Sarepta, Inc. During the most recent 6-month period JG has received compensation from Aetna, MacMillan Publishing, and Access Health, International. AL reports personal investments in private biotech companies, biotech venture capital funds, and mutual funds. AL is a co-founder and partner of QLS Advisors, a healthcare analytics and consulting company; an advisor to Apricity Health, Aracari Bio, BrightEdge Impact Fund, Enable Medicine, Inc, FINRA, Health at Scale, Lazard, MIT Proto Ventures, Quantile Health, Roivant Social Ventures, SalioGen Therapeutics, Swiss Finance Institute, Thalēs, and xCures; a director of AbCellera, Annual Reviews, Atomwise, BridgeBio Pharma, Uncommon Cures, and Vesalius. During the most recent six-year period (beginning 2017), AL received speaking/consulting fees, honoraria, or other forms of compensation from: AbCellera, AlphaSimplex Group, Annual Reviews, Apricity Health, Aracari Bio, Atomwise, Bernstein Fabozzi Jacobs Levy Award, BridgeBio, Cambridge Associates, Chicago Mercantile Exchange, Enable Medicine, Financial Times Prize, Harvard Kennedy School, IMF, Journal of Investment Management, Lazard, National Bank of Belgium, New Frontier Advisors/Markowitz Award, Oppenheimer, Princeton University Press, Q Group, QLS Advisors, Quantile Health, Research Affiliates, Roivant Sciences, SalioGen, Swiss Finance Institute, and WW Norton.

Footnotes

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

The online version contains supplementary material available at 10.1038/s41434-023-00419-9.

References

1. Spinraza® and Onasemnogene abeparvovec-xioi ® for spinal muscular atrophy: Effectiveness and Value, Final Evidence Report [Internet]. Boston, MA: Institute for Clinical and Economic Review; 2019 Apr; [cited 2022 Dec 7]. Available from: https://icer.org/wp-content/uploads/2020/10/ICER_SMA_Final_Evidence_Report_052419.pdf

2. Voretigene Neparvovec for Biallelic RPE65-Mediated Retinal Disease: Effectiveness and Value, Final Evidence Report [Internet]. Boston, MA: Institute for Clinical and Economic Review; 2018 Feb [cited 2022 Dec 7]. Available from: https://icer.org/wp-content/uploads/2020/10/MWCEPAC_VORETIGENE_FINAL_EVIDENCE_REPORT_02142018.pdf

3. Abrantes-Metz RM, Adams C, Metz AD. Pharmaceutical development phases: a duration analysis. J Pharm Finance Econ Policy. 2005; 14 :19–42. doi: 10.1300/J371v14n04_03. [ CrossRef ] [ Google Scholar ]

4. DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016; 47 :20–33. doi: 10.1016/j.jhealeco.2016.01.012. [ PubMed ] [ CrossRef ] [ Google Scholar ]

5. Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019; 20 :273–86. doi: 10.1093/biostatistics/kxx069. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]

6. Guzman G. New Data Show Income Increased in 14 States and 10 of the Largest Metros [Internet]. United States Census Bureau. 2019 [cited 2022 Dec 7]. Available from: https://www.census.gov/library/stories/2019/09/us-median-household-income-up-in-2018-from-2017.html

7. Chambers JD, Panzer AD, Kim DD, Margaretos NM, Neumann PJ. Variation in US private health plans’ coverage of orphan drugs. Am J Manag Care. 2019; 25 :508–12. [ PubMed ] [ Google Scholar ]

8. Thomas S. How are insurers treating the $2M drug, onasemnogene abeparvovec-xioi ? [Internet]. Policy & Medicine. 7. Available from: https://www.policymed.com/2019/10/how-are-insurers-treating-the-2m-drug-zolgensma.html .

9. Jennifer T, Kendal O, Damico A. Key facts about the uninsured population [Internet]. Kaiser Family Foundation. Kaiser Family Foundation; 2020 [cited 2022 Dec 7]. Available from: https://www.kff.org/uninsured/issue-brief/key-facts-about-the-uninsured-population/

10. Collins SR, Bhupal HK, Doty MM. Health insurance coverage eight years after the ACA: fewer uninsured Americans and shorter coverage gaps, but more underinsured. The Commonwealth Fund Issue briefs. February 7, 2019. Available from: https://www.commonwealthfund.org/publications/issue-briefs/2019/feb/health-insurance-coverage-eight-years-after-aca

11. Quinn C, Young C, Thomas J, Trusheim M, NEWDIGS MIT. Estimating the clinical pipeline of cell and gene therapies and their potential economic impact on the US healthcare system. Value Health. 2019; 22 :621–6. doi: 10.1016/j.jval.2019.03.014. [ PubMed ] [ CrossRef ] [ Google Scholar ]

12. Tozzi J. Employers fear squeeze from genetic cures that cost millions, September 2019. Bloomberg News Agency [Internet]. 2019 Sep;04–10. Available from: https://www.bloomberg.com/news/articles/2019-09-11/employers-fear-squeeze-from-genetic-cures-that-cost-millions?leadSource=uverify%20wall

13. Auerbach DI, Kellermann AL. A decade of health care cost growth has wiped out real income gains for an average US family. Health Aff (Millwood) 2011; 30 :1630–6. doi: 10.1377/hlthaff.2011.0585. [ PubMed ] [ CrossRef ] [ Google Scholar ]

14. FDA. Expanded Access | Information for Industry [Internet]. 2019. Available from: https://www.fda.gov/news-events/expanded-access/expanded-access-information-industry

15. Jarow JP, Lemery S, Bugin K, Khozin S, Moscicki R. Expanded access of investigational drugs: the experience of the center of drug evaluation and research over a 10-year period. Ther Innov Regul. Sci. 2016; 50 :705–9. doi: 10.1177/2168479016656030. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]

16. Ann Meeker O, Anthony FA, Caitilin H, Jessica Z. Global approaches to drug development: when Ex-Us Clinical Data Can Support US Drug Approvals [Internet]. IQVIA White Paper. 2019. Available from: https://www.iqvia.com/library/white-papers/global-approaches-to-drug-development

17. MIT Laboratory for Financial Engineering. Estimates of Clinical Trial Probabilities of Success (PoS) [Internet]. Project ALPHA. 2019. Available from: https://projectalpha.mit.edu/pos/

18. U.S. Food and Drug AdministrationFood US, Administration D. CFR - Code of Federal Regulations Title 21 [Internet]. 2019. Available from: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=314.101

19. US Food and Drug AdministrationFood US, Administration D. Step 4: FDA Drug Review [Internet]. 2018. Available from: https://www.fda.gov/patients/drug-development-process/step-4-fda-drug-review

20. U.S. Census Bureau. U.S. Census Bureau QuickFacts: United States [Internet]. 2019. Available from: https://www.census.gov/quickfacts/fact/table/US/PST045219

21. Neumann PJ, Cohen JT, Weinstein MC. Updating cost-effectiveness—the curious resilience of the $50,000-per-QALY threshold. N Engl J Med [Internet] 2014; 371 :796–7. doi: 10.1056/NEJMp1405158. [ PubMed ] [ CrossRef ] [ Google Scholar ]

22. Council CEPA. ICER reports on spinal muscular atrophy and CVD therapies. PharmacoEcon Outcomes News. 2019; 823 :1–9. doi: 10.1007/s40274-019-5691-2. [ CrossRef ] [ Google Scholar ]

23. Miller J, Humer C. Novartis $2 million gene therapy for rare disorder is world’s most expensive drug. Reuters Healthcare & Pharma [Internet]. 2019 May 24 [cited 2022 Dec 7]; Available from: https://www.reuters.com/article/us-novartis-genetherapy/novartis-2-million-gene-therapy-for-rare-disorder-is-worlds-most-expensive-drug-idUSKCN1SU1ZP

24. Tirrell MA. US drugmaker offers to cure rare blindness for $850,000 [Internet]. CNBC. 2018 Available from: https://www.cnbc.com/2018/01/03/spark-therapeutics-luxturna-gene-therapy-will-cost-about-850000.html

25. Andrews M Staggering Prices Slow Insurers’ Coverage Of CAR-T Cancer Therapy [Internet]. Kaiser Health News. Kaiser Health News; 2018 [cited 2022 Dec 7]. Available from: https://khn.org/news/staggering-prices-slow-insurers-coverage-of-car-t-cancer-therapy/

26. Kaiser Family Foundation. Medicaid State Fact Sheets [Internet]. Kaiser Family Foundation. 2022 [cited 2022 Dec 7]. Available from: https://www.kff.org/interactive/medicaid-state-fact-sheets/

27. Cook K, Forbes SP, Adamski K, Ma JJ, Chawla A, Garrison LP., Jr Assessing the potential cost-effectiveness of a gene therapy for the treatment of hemophilia A. J Med Econ. 2020; 23 :501–12. doi: 10.1080/13696998.2020.1721508. [ PubMed ] [ CrossRef ] [ Google Scholar ]

28. Sarpatwari A, DiBello J, Zakarian M, Najafzadeh M, Kesselheim AS. Competition and price among brand-name drugs in the same class: a systematic review of the evidence. PLoS Med. 2019; 16 :e1002872. doi: 10.1371/journal.pmed.1002872. [ PMC free article ] [ PubMed ] [ CrossRef ] [ Google Scholar ]

29. Gelijns AC, Halm EA. The Diffusion of New Technology: Costs and Benefits to Health Care. In: The Changing Economics of Medical Technology. National Academies Press (US); 1991. [ PubMed ] [ Google Scholar ]

30. Institute for Clinical and Economic Review E. ICER’s 2020–2023 Update: Value Assessment Framework [Internet]. Institute for Clinical and Economic Review. 2020 [cited 2022 Dec 7]. Available from: https://icer-review.org/material/2020-value-assessment-framework-final-framework/

31. Park J, Look KA. Health care expenditure burden of cancer care in the United States. Inq J Health Care Organ Provis Financ. 2019; 56 :0046958019880696. [ PMC free article ] [ PubMed ] [ Google Scholar ]

32. Congressional Budget Office. The budget and economic outlook: 2019 to 2029. Congress of the United States, Congressional Budget Office. Washington, DC; 2019.

33. Centers for Medicare & Medicaid Services. NHE Fact Sheet [Internet]. CMS.gov. [cited 2022 Dec 7]. Available from: https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/NHE-Fact-Sheet

34. Brennan TA, Wilson JM. The special case of gene therapy pricing. Nat Biotechnol. 2014; 32 :874–6. doi: 10.1038/nbt.3003. [ PubMed ] [ CrossRef ] [ Google Scholar ]

35. Montazerhodjat V, Weinstock D, Lo AW. Buying cures vs. renting health: financing healthcare via consumer loans. Sci Transl Med. 2016; 8 :327ps6. doi: 10.1126/scitranslmed.aad6913. [ PubMed ] [ CrossRef ] [ Google Scholar ]

36. Cigna. Embarc benefit protection program. [Internet]. [cited 2022 Dec 7]. Available from: https://www.cigna.com/employers/cost-control/embarc-benefit-protection

37. Barlow JF, Yang M, Teagarden JR. Are payers ready, willing, and able to provide access to new durable gene therapies? Value Health. 2019; 22 :642–7. doi: 10.1016/j.jval.2018.12.004. [ PubMed ] [ CrossRef ] [ Google Scholar ]

38. U.S. Health and Human Services, Center for Medicare and Medicaid Innovation. ‘Lowering Prescription Drug Costs for Americans, Response to President Biden’s Executive Order.’ February 2023. Available from: https://www.cms.gov/priorities/innovation/data-and-reports/2023/eo-rx-drug-cost-response-report

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