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Affordability of in vivo gene therapy. Problems and potential solutions

https://doi.org/10.17749/2070-4909/farmakoekonomika.2020.040

Abstract

Aim. To review foreign approaches to the evaluation and financing of in vivo gene therapy drugs.

Materials and Methods. The first stage of the review included the systematic search for publications of clinical-economic studies (CES) on in vivo gene therapy drugs registered on the international pharmaceutical market. The analysis of the methodology used in the found CESs was performed based on the given criteria. The second and third stages of the review included the search for the information on the approaches and results of the evaluation of in vivo gene therapy drugs by foreign agencies on the assessment of healthcare technologies (AHT) and the implemented approaches to the financing of expensive medical technologies.

Results. Totally, four in vivo gene therapy drugs registered on the foreign markets were found: talimogene laherparepvec (Imlygic), voretigene neparvovec (Luxturna), onasemnogene abeparvovec (Zolgensma), and alipogene tiparvove (Glybera). The analysis of the methodology of CES on in vivo gene therapy drugs did not reveal general methodological peculiarities. The analysis of the approaches to the reimbursement for the cost of these four drugs in the European countries showed that there were no special procedures intended for gene drugs. However, in the majority of countries, there are some mechanisms of reimbursement for orphan drugs and the majority of the above-mentioned in vivo gene therapy drugs are orphan. It was revealed that the most perspective methods of payment for in vivo gene therapy drugs were installment payments, risk-sharing agreements, and their combinations. Still, none of these payment methods are implemented in Russia because of the lack of regulatory and legal framework.

Conclusion. The design and methodological peculiarities of CES on in vivo gene therapy drugs are similar to orphan drugs (in some countries, there is a special flexible procedure). In the Russian Federation, there is no special procedure of ATH for orphan drugs, which can provide difficulties in the reimbursement for these drugs. Besides, in the Russian Federation, the issue of the implementation of innovative models for drugs provision (risk-sharing, installment payments is acute). The changes in this area would also lead to the optimization of the influence of expensive healthcare technologies on the budget of the system of healthcare.

About the Authors

V. V. Omelyanovskiy
Center for Healthcare Quality Assessment and Control of the Ministry of Healthcare of the Russian Federation; Financial Research Institute of the Ministry of Finance of the Russian Federation; Russian Medical Academy of Postgraduate Education, Moscow
Russian Federation

MD, Dr Sci Med, Professor, General Director, Head of the Center for Healthcare Funding

Researcher ID: P-6911-2018; Scopus Author ID: 6507287753  

10-5 Khokhlovsky per., Moscow 109028, Russia

3-2 Nastasyinsky per., Moscow 127006, Russia

2-1 Barrikadnaya str., Moscow 123995, Russia



N. Z. Musina
Center for Healthcare Quality Assessment and Control of the Ministry of Healthcare of the Russian Federation; Saint Petersburg State Chemical Pharmaceutical University; Russian Presidential Academy of National Economy and Public Administration
Russian Federation

PhD (Pharmaceutical Sciences), Associate Professor at the Department of management; Head of the HTA Research Laboratory of the Institute for Applied Economic Research; Head of Development 

Researcher ID: C-8075-2018  

10-5 Khokhlovsky per., Moscow 109028, Russia

14 let. A Prof. Popov str., Saint Petersburg 197376, Russian Federation

82 Vernadskogo pr., Moscow 119571, Russia



V. A. Lemeshko
Center for Healthcare Quality Assessment and Control of the Ministry of Healthcare of the Russian Federation; Financial Research Institute of the Ministry of Finance of the Russian Federation; Institute of Pharmacy and Translational Medicine, Sechenov University
Russian Federation

Deputy Head of the Department of Methodological Support of Comprehensive Health Technology Assessment; Research assistant at the Center for Healthcare Funding; Post-graduate student at the Department of Pharmacology, Educational Department

Researcher ID: AAD-8959-2019  

10-5 Khokhlovsky per., Moscow 109028, Russia

3-2 Nastasyinsky per., Moscow 127006, Russia

8-2 Trubetskaya str., Moscow 119991, Russia



A. A. Antonov
Center for Healthcare Quality Assessment and Control of the Ministry of Healthcare of the Russian Federation
Russian Federation

Lead Specialist, Department of Methodological Support for Comprehensive HTA

10-5 Khokhlovsky per., Moscow 109028, Russia



F. V. Gorkavenko
Center for Healthcare Quality Assessment and Control of the Ministry of Healthcare of the Russian Federation
Russian Federation

Chief Specialist, Department of Methodological Support for Comprehensive HTA

Researcher ID: A-8805-2017

10-5 Khokhlovsky per., Moscow 109028, Russia



References

1. REGULATION (EC) No 1394/2007. On advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004. Official Journal of the European Union. 2007; 121–137.

2. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use. OJ L 311, 28.11.2001, p. 67–128 [Electronic resource] URL: https://eur-lex.europa.eu/legal-content/en/ALL/?uri=CELEX%3A32001L0083 Accessed: 17.10.2019.

3. Federal law dated 12.04.2010 N 61-ФЗ (as amended on 02.08.2019) “On the circulation of medicines” (in Russ).

4. Neovasculgen. Instructions for the medical use of the drug. LP-000671. State register of medicines. [Electronic resource]. URL: http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=872be3da-4673-4047-8931-a26680b74b96&t=. Accessed: 17.10.2019 (in Russ).

5. Senior M. After Glybera’s withdrawal, what’s next for gene therapy? Nature Biotechnology. 2017; 35 (6): 491–492. DOI: https://doi.org/10.1038/nbt0617-491.

6. The state register of maximum selling prices. Neovasculgen. [Electronic URL: URL: http://grls.rosminzdrav.ru/PriceLims.aspx?Torg=Neovaskulgen&Mnn=&RegNum=&Mnf=&Barcode=&Order=&PageSize=8&orderby=pklimprice&orderType=desc&pagenum=1. Accessed: 17.10.2019 (in Russ).

7. Touchot N., Flume M. Early insights from commercialization of gene therapies in Europe. Genes (Basel). 2017; 8 (2): 2–5.

8. Bundesausschuss G. Zugelassenes Anwendungsgebiet (laut Zulassung vom 16.12.2015): IMLYGIC ® ist indiziert zur Behandlung von Erwachsenen mit nicht resezierbarem, lokal oder entfernt metastasiertem Melanom (Stadium IIIB, IIIC und IVM1a) ohne Knochen-, Hirn-, Lungen-oder ande [Electronic resource]. URL: https://www.g-ba.de/downloads/91-1385-243/2016-12-15_Geltende-Fassung_Talimogen-laherparepvec_D-237.pdf. Accessed: 17.10.2019.

9. FDA approves Imlygic (talimogene laherparepvec) as first oncolytic viral therapy in the US. Press release. [Electronic resource]. URL: https://www.amgen.com/media/news-releases/2015/10/fdaapproves-imlygic-talimogene-laherparepvec-as-first-oncolytic-viraltherapy-in-the-us/. Accessed: 17.10.2019.

10. Voretigene neparvovec for treating inherited retinal dystrophies caused by RPE65 gene mutations. Highly specialised technologies guidance. NICE. 2019. [Electronic resource] URL: https://www.nice.org.uk/guidance/hst11. Accessed: 17.10.2019.

11. Pagliarulo N. Novartis secures NICE nod for Luxturna with discount offer. BioPharma Dive. [Electronic resource]. URL: https://www.biopharmadive.com/news/nice-luxturna-gene-therapy-ecommendationnovartis-discount/562211/. Accessed: 17.10.2019.

12. Zolgensma cost: gene therapy funding expected to normalise over time/ Pharmaceutical Technology. 22.07.2019. [Electronic resource]. URL: https://www.pharmaceutical-technology.com/comment/zolgensma-cost/. Accessed: 17.10.2019.

13. Almutairi A.R. et al. Economic Evaluation of Talimogene Laherparepvec Plus Ipilimumab Combination Therapy vs Ipilimumab Monotherapy in Patients with Advanced Unresectable Melanoma. JAMA Dermatology. 2019; 155 (1): 22–28.

14. Fleeman N. et al. Talimogene Laherparepvec for Treating Metastatic Melanoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Pharmacoeconomics. 2017; 35 (10): 1035–1046.

15. Zimmermann M. et al. Cost Utility of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease. Value Heal. 2019; 22 (2): 161–167.

16. Johnson S.et al. Cost-effectiveness of Voretigene Neparvovecrzyl vs Standard Care for RPE65 – Mediated Inherited Retinal Disease. JAMA Ophthalmol. 2019; 02186.

17. Malone D.C. et al. Cost-effectiveness analysis of using onasemnogene abeparvocec (AVXS-101) in spinal muscular atrophy type 1 patients. J. Mark. Access & Heal. Policy. 2019; 7 (1): 1601484.

18. Han X., Ni W. Cost-Effectiveness Analysis of Glybera for The Treatment of Lipoprotein Lipase Deficiency. Value Heal. 2015; 18 (7): A756.

19. Melanoma kozhi i slizistykh obolochek. Klinicheskie rekomendatsii. Minzdrav Rossii. 2019; KR546/1. 164 s. [Electronic resource]. URL: http://cr.rosminzdrav.ru/#!/recomend/766. Accessed: 17.10.2019.

20. Luxturna (voretigene neparvovec) meeting of the cellular, tissue, and gene therapies advisory committee. FDA advisory committee briefing document. Spark Therapeutic. 2017; [Electronic resource]. URL: https://www.fda.gov/media/108385/download. Accessed: 17.10.2019.

21. Verhaart I.E.C. et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy – a literature review. Orphanet J Rare Dis. 2017 Jul 4; 12 (1): 124.

22. Familial lipoprotein lipase deficiency. U.S. National Library of Medicine. [Electronic resource]. URL: https://ghr.nlm.nih.gov/condition/familial-lipoprotein-lipase-deficiency#statistics. Accessed: 17.10.2019.

23. Transparency Committee Doctrine. Principles of medicinal products assessment and appraisal for reimbursement purposes. Haute Autorité de Santé. 2018; [Electronic resource]. URL: https://www.has-sante.fr/upload/docs/application/pdf/2019-07/doctrine_de_la_commission_de_la_transparence_-_version_anglaise.pdf. Accessed: 17.10.2019.

24. Wenzl M., Paris V. Pharmaceutical reimbursement and pricing in Germany. OECD. 2018 [Electronic resource]. URL: https://www.oecd.org/health/health-systems/Pharmaceutical-Reimbursement-andPricing-in-Germany.pdf. Accessed: 17.10.2019.

25. National Institute for Health and Care Excellence. Technology appraisal processes. NICE. [Electronic resource]. URL: https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nicetechnology-appraisal-guidance/process. Accessed: 17.10.2019.

26. How we make our decisions. Scottish Medicines Consortium. [Electronic resource]. URL: https://www.scottishmedicines.org.uk/how-we-decide/. Accessed: 17.10.2019.

27. Revised process– ultra-orphanmedicines for extremely rare conditions. Scottish Medicines Consortium. [Electronic resource]. URL: https://www.scottishmedicines.org.uk/how-we-decide/revised-process-ultra-orphanmedicines-for-extremely-rare-conditions/. Accessed: 17.10.2019.

28. Alipogene tiparvovec – Assessment according to §35a (para. 1., sentence 10) Social Code Book V (dossier assessment). Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen. [Electronic resource]. URL: https://www.crd.york.ac.uk/crdweb/ShowRecord.asp?ID=32015001044&ID=32015001044. Accessed: 17.10.2019.

29. Talimogene laherparepvec – Extract of dossier assessment – Version 1.0. Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen. 2016; September: 8.

30. Nutzenbewertungsverfahren zum Wirkstoff Voretigen Neparvovec (Erbliche Netzhautdystrophie). Gemeinsamer Bundesausschuss [Electronic resource]. URL: https://www.g-ba.de/bewertungsverfahren/nutzenbewertung/454/. Accessed: 17.10.2019.

31. Glybera (alipogene tiparvovec), gene therapy. Brief summary of the transparency committee opinion. Haute Autorité de Santé. 2015; [Electronic resource] URL: https://www.has-sante.fr/upload/docs/application/pdf/2016-05/glybera_summary_ct14224.pdf. Accessed: 17.10.2019

32. Luxturna (voretigene neparvovec). Transparency committee opinion summary. Haute Autorité de Santé. 2019; [Electronic resource] URL: https://www.has-sante.fr/upload/docs/application/pdf/2019-08/luxturna_summary_ct17535.pdf. Accessed: 17.10.2019

33. Talimogene laherparepvec for treating unresectable metastatic melanoma. Technology appraisal guidance. National Institute for Health and Care Excellence. 2016. [Electronic resource] URL: https://www.nice.org.uk/guidance/ta410/documents/appraisal-consultationdocument. Accessed: 17.10.2019

34. National Institute for Health and Care Excellence Final appraisal document. Voretigene neparvovec for treating inherited retinal dystrophies caused by RPE65 gene mutations. 2019.

35. Statement of Advice: talimogene laherparepvec (Imlygic) (No: 1248/17). Scottish Medicines Consortium. 2017.

36. Voretigene neparvovec (Luxturna). Scottish Medicines Consortium. [Electronic resource] URL: https://www.scottishmedicines.org.uk/medicines-advice/voretigene-neparvovec-luxturna-uoiasmc2228/. Accessed: 17.10.2019

37. Bubela T., McCabe C. Value-engineered translation for regenerative medicine: meeting the needs of health systems. Stem Cells Dev. Mary Ann Liebert, Inc. 140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA, 2013; 22 (S1): 89–93.

38. Hampson G. et al. Gene therapy: evidence, value and affordability in the US health care system. J. Comp. Eff. Res. Future Medicine. 2018; 7 (1): 15–28.

39. Morrow D., Ussi A., Migliaccio G. Addressing pressing needs in the development of advanced therapies. Front. Bioeng. Biotechnol. Frontiers. 2017; 5: 55.

40. Spoors J., Croft E., Walker A. Regeneration X: The payer perspective on gene therapy. Br. J. Healthc. Manag. MA Healthcare London. 2017; 23 (4): 158–166.

41. Daniel G. et al. Advancing gene therapies and curative health care through value-based payment reform. Heal. Aff. Blog. 2017.

42. Narayanan G. Translation and Reimbursement: The Twin Challenges for Cell and Gene Therapies Reflections of an Ex-Regulator. Hum Gene Ther Clin Dev. 2016 Sep; 27 (3): 93–5.

43. Mihos M., Faulkner E., Solutions E. Leveraging Real-World Evidence for Regenerative Medicine and Advanced Therapy Success Beyond the Regulator. Redefining Drug Dev. 2017; P. 20.

44. Marsden G. et al. Gene therapy: understanding the science, assessing the evidence, and paying for value. 2017.

45. Getting Ready: Recommendations for Timely Access to Advanced Therapy Medicinal Products (ATMPs) in Europe. Alliance Regen. Med. 2019.

46. Slocomb T. et al. New payment and financing models for curative regenerative medicines. Vivo Pharma Intell. July/August. 2017.

47. Cook F., Slocomb T., Werner M. Regenerative Medicine Is Here: New Payment Models Key To Patient Access. In Vivo (Brooklyn). 2018; P. 6.

48. Zalmoxis. European medicines agency. [Electronic resource] URL: https://www.ema.europa.eu/en/medicines/human/EPAR/zalmoxis. Accessed: 17.10.2019.


Review

For citations:


Omelyanovskiy V.V., Musina N.Z., Lemeshko V.A., Antonov A.A., Gorkavenko F.V. Affordability of in vivo gene therapy. Problems and potential solutions. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020;13(2):170-182. (In Russ.) https://doi.org/10.17749/2070-4909/farmakoekonomika.2020.040

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