Economic outcomes of centralized procurements of gene therapy for patients with orphan diseases: inherited retinal dystrophy

Background. New pathogenetic treatment options, such as gene therapy, are now used to treat previously uncurable diseases. However, price of such treatment is high, especially in the case of orphan diseases, where costs may many-fold exceed the prices for other types of medication. This raises a question of optimal way of financing gene therapy in Russia.
Objective: to evaluate economic consequences of centralizing procurement of gene therapy in 2021–2030 in the case of the drug indicated for treatment of biallelic RPE65 mutation-associated retinal dystrophy.
Material and methods. Voretigene neparvovec is a new gene therapy that is used to treat RPE65 mutation-associated Leber congenital amaurosis and isolated retinitis pigmentosa. We estimated the number of patients (children and adults) that could be treated with voretigene neparvovec in 2021–2030 in Russia using demographic forecasting method, literature and expert data. Budget costs of treatment were estimated for two scenarios: status-quo, where gene therapy is purchased by regions for higher price, and centralized scenario with federal procurements and lower price for the drug.
Results. Up to 100 children and 56 adults could be treated with voretigene neparvovec in 2021–2030 in Russia. Centralizing procurements at the expense of federal budget may save up to 20.7% or 1.8 billion rub. (1.13 billion rub. for children and 0.67 billion rub. for adults), compared to regional procurements.
Conclusion. Centralizing procurements of expensive drugs intended for gene therapy of orphan diseases may save budget costs of the Russian Federation, compared to status-quo decentralized purchases.

1. Goryaev A.A., Savkina M.V., Mefed K.M., et al. Genome-editing and biomedical cell products: current state, safety and efficacy. BIOpreparations. Prevention, Diagnosis, Treatment. 2018; 18 (3): 140–9 (in Russ.). https://doi.org/10.30895/2221-996X-2018-18-3-140-149.

2. Nekhorosheva А.А., Popova T.S., Batishcheva Yu.S., Kolbenev I.O. Modern aspects of diagnostics and monitoring of tape-toretinal degeneration. Saratov Journal of Medical Scientific Research. 2017; 13 (2): 422–6 (in Russ.).

3. Ivanova M.E., Tikhonovich M.V., Zolnikova I.V. Modern approaches to gene therapy of retinal dystrophies. Russian Ophthalmological Journal. 2013; 6 (4): 103–10 (in Russ.).

4. Russell S., Bennett J., Wellman J.A., et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65- mediated inherited retinal dystrophy: a randomised, controlled, openlabel, phase 3 trial. Lancet. 2017; 390 (10097): 849–60. https://doi.org/10.1016/S0140-6736(17)31868-8.

5. List of rare (orphan) diseases dated March 4, 2021. Available at: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/054/896/original/Перечень_орфанов_04.03.2021.xlsx?1614861777 (in Russ.) (accessed 21.05.2021).

6. Resolution of the Government of the Russian Federation No. 403 of 26.04.2012 “On the procedure for maintaining the Federal Register of persons suffering from life-threatening and chronic progressive rare (orphan) diseases that lead to a reduction in the life expectancy of citizens or their disability, and its regional segment”. Available at: https://base.garant.ru/70168888/ (in Russ.) (accessed 21.05.2021).

7. Decree of the Government of the Russian Federation No. 2406-r of 12.10.2019 “On approval of the list of vital and essential medicines, as well as lists of medicines for medical use and the minimum range of medicines required for medical care”. Available at: http://www.consultant.ru/document/cons_doc_LAW_335635/a2556028998984160bf9455f2573572c3cc33f3f/ (in Russ.) (accessed 21.05.2021).

8. Circle of Goodness. List of severe life-threatening and chronic diseases, including rare (orphan) diseases. Available at: https://фондкругдобра.рф/lists#rec287114063 (in Russ.) (accessed 09.09.2021).

9. Resolution of the Government of the Russian Federation No. 769 of 05.21.2021 “On approval of the rules for providing medical care (if necessary outside the Russian Federation) to a specific child with a serious life-threatening or chronic disease, including a rare (orphan) disease, or groups of such children”. Available at: https://www.garant.ru/products/ipo/prime/doc/400694260/ (accessed 09.09.2021).

10. Phelan J.K., Bok D. A brief review of retinitis pigmentosa and the identified retinitis pigmentosa genes. Mol Vis. 2000; 6: 116–24.

11. Stone E.M. Leber congenital amaurosis – a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture. Am J Ophthalmol. 2007; 144 (6): 791–811. https://doi.org/10.1016/j.ajo.2007.08.022.

12. Chung D.C., Traboulsi E.I. Leber congenital amaurosis: clinical correlations with genotypes, gene therapy trials update, and future directions. J AAPOS. 2009; 13 (6): 587–92. https://doi.org/10.1016/j.jaapos.2009.10.004.

13. Morimura H., Fishman G.A., Grover S.A., et al. Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or leber congenital amaurosis. Proc Natl Acad Sci USA. 1998; 95 (6): 3088–93. https://doi.org/10.1073/pnas.95.6.3088.

14. Zinchenko R.A., Makaov A.Kh., Marakhonov A.V., et al. Epidemiology of hereditary diseases in the Karachay–Cherkess republic. Int J Mol Sci. 2020; 21 (1): 325. https://doi.org/10.3390/ijms21010325.

15. Zinchenko R.A., Elchinova G.I., Osipova E.V., et al. Population genetics of hereditary diseases in the Udmurt Republic. Bulletin of Udmurt University. Series Biology. Earth Sciences. 2009; 1: 43–58 (in Russ.).

16. Zinchenko R.A., El'chinova G.I., Baryshnikova N.V., et al. Prevalences of hereditary diseases in different populations of Russia. Genetika. 2007; 43 (9): 1246–54 (in Russ.).

17. All-Russian Population Census 2010. National composition of the population. Available at: https://www.gks.ru/free_doc/new_site/perepis2010/croc/Documents/Vol4/pub-04-01.xlsx (in Russ.) (accessed 02.04.2021).

18. Unified Interdepartmental Information and Statistical System. The number of permanent population on average per year. Available at: https://fedstat.ru/indicator/31556 (in Russ.) (accessed 02.04.2021).

19. Center for Demographic Research, Russian School of Economics. Average annual population by regions of Russia for calculating mortality rates by one-year age groups, 1989–2014. Available at: http://demogr.nes.ru/images/uploads/PopDa1989-2014.zip (in Russ.) (accessed 02.04.2021).

20. Zol’nikova I.V., Milash S.V., Chernyak A.B., et al. Thickness of the retinal photoreceptor layers and the choroid, and bioelectrical activity of the macula in retinitis pigmentosa. Vestnik Oftalmologii. 2019; 135 (3): 39–45 (in Russ.). https://doi.org/10.17116/oftalma201913503139.

21. Center for Demographic Research, Russian School of Economics. Russia and regions, one-year age groups, 2015–2019. Available at: http://demogr.nes.ru/images/uploads/DRa2015-2019.zip (in Russ.) (accessed 14.06.2021).

22. Aouadj C., Bamhazi J., Shaikh J., et al. PSY28 – Epidemiology of RPE65 gene mutation related inherited retinal dystrophies: a systematic literature review. Value in Health. 2018; 21 (Suppl. 3) S440. https://doi.org/10.1016/j.jval.2018.09.2605.

23. The portal for rare diseases and orphan drugs. Available at: https://www.orpha.net/consor/cgi-bin/index.php (accessed 20.10.2021).

24. Genotek Laboratory. Analysis of disease panels. Available at: https://www.genotek.ru/diagnostic/panels/ (in Russ.) (accessed 02.04.2021).

25. Bochkov Research Centre of Medical Genetics. Available at: https://med-gen.ru (in Russ.) (accessed 02.04.2021).

26. Yagudina R.I., Kulikov A.Yu., Ugrekhelidze D.T. Assessing willingness-to-pay threshold for health technologies in the Russian Federation on the basis of purchasing power parity. Pharmacoeconomics: Theory and Practice. 2015; 3 (3): 5–9 (in Russ.).