Public Risk-Taking and Rewards During the COVID-19 Pandemic - A Case Study of Remdesivir in the Context of Global Health Equity

Document Type : Short Communication

Authors

1 University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

2 Harvey E. Beardmore Division of Pediatric Surgery, The Montreal Children’s Hospital, McGill University Health Centre, Montreal, QC, Canada

3 Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

4 Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, UK

Abstract

Public investment, through both research grants and university funding, plays a crucial role in the research and development (R&D) of novel health technologies, including diagnostics, therapies, and vaccines, to address the coronavirus disease 2019 (COVID-19) pandemic. Using the example of remdesivir, one of the most promising COVID-19 treatments, this paper traces back public contributions to different stages of the innovation process. Applying the Risk-Reward Nexus framework to the R&D of remdesivir, we analyse the role of the public in risk-taking and reward and address inequities in the biomedical innovation system. We discuss the collective, cumulative and uncertain characteristics of innovation, highlighting the lack of transparency in the biomedical R&D system, the need for public investment in the innovation process, and the “time-lag” between risk-taking and reward. Despite the significant public transnational contributions to the R&D of remdesivir, the rewards are extracted by few actors and the return to the public in the form of equitable access and affordable pricing is limited. Beyond the necessity to treat remdesivir as a global public good, we argue that biomedical innovation needs to be viewed in the broader concept of public value to prevent the same equity issues currently seen in the COVID-19 pandemic. This requires the state to take a market-shaping rather than market-fixing role, thereby steering innovation, ensuring that patents do not hinder global equitable access and affordable pricing and safeguarding a global medicines supply.

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Main Subjects


  1. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. Johns Hopkins University website. https://coronavirus.jhu.edu/map.html.  Accessed July 22, 2020. Published 2020.
  2. Thanh Le T, Andreadakis Z, Kumar A, et al. The COVID-19 vaccine development landscape. Nat Rev Drug Discov. 2020;19(5):305-306. doi:10.1038/d41573-020-00073-5
  3. Tracking Public Investment in Global COVID-19 Research and Development. Universities Allied for Essential Medicines website. https://www.publicmeds4covid.org.  Accessed July 22, 2020. Published 2020.
  4. Health Topics - Innovation. World Health Organization website. https://www.who.int/topics/innovation/en/.  Accessed July 22, 2020.
  5. Webb Hooper M, Nápoles AM, Pérez-Stable EJ. COVID-19 and racial/ethnic disparities. JAMA. 2020;323(24):2466-2467. doi:10.1001/jama.2020.8598
  6. Abrams EM, Szefler SJ. COVID-19 and the impact of social determinants of health. Lancet Respir Med. 2020;8(7):659-661. doi:10.1016/s2213-2600(20)30234-4
  7. Shadmi E, Chen Y, Dourado I, et al. Health equity and COVID-19: global perspectives. Int J Equity Health. 2020;19(1):104. doi:10.1186/s12939-020-01218-z
  8. Lazonick W, Mazzucato M. The risk-reward nexus in the innovation-inequality relationship: who takes the risks? who gets the rewards? Ind Corp Change. 2013;22(4):1093-1128. doi:10.1093/icc/dtt019
  9. Health Topics - Health Equity. World Health Organization website. https://www.who.int/topics/health_equity/en/.  Accessed July 22, 2020.
  10. Knowledge Ecology International (KEI). Role of the Federal Government in the Development of Remdesivir. https://www.keionline.org/wp-content/uploads/KEI-Briefing-Note-2020_1GS-5734-Remdesivir.pdf. Published 2020.
  11. Public Citizen. The Real Story of Remdesivir. https://www.citizen.org/wp-content/uploads/The-Real-Story-of-Remdesivir-final-May-7.pdf. Published 2020.
  12. Cho A, Saunders OL, Butler T, et al. Synthesis and antiviral activity of a series of 1'-substituted 4-aza-7,9-dideazaadenosine C-nucleosides. Bioorg Med Chem Lett. 2012;22(8):2705-2707. doi:10.1016/j.bmcl.2012.02.105
  13. Warren TK, Jordan R, Lo MK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016;531(7594):381-385. doi:10.1038/nature17180
  14. Jacobs M, Rodger A, Bell DJ, et al. Late Ebola virus relapse causing meningoencephalitis: a case report. Lancet. 2016;388(10043):498-503. doi:10.1016/s0140-6736(16)30386-5
  15. Sheahan TP, Sims AC, Graham RL, et al. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017;9(396). doi:10.1126/scitranslmed.aal3653
  16. Lo MK, Jordan R, Arvey A, et al. GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses. Sci Rep. 2017;7:43395. doi:10.1038/srep43395
  17. Dörnemann J, Burzio C, Ronsse A, et al. First newborn baby to receive experimental therapies survives Ebola virus disease. J Infect Dis. 2017;215(2):171-174. doi:10.1093/infdis/jiw493
  18. Siegel D, Hui HC, Doerffler E, et al. Discovery and synthesis of a phosphoramidate prodrug of a Pyrrolo[2,1-f][triazin-4-amino] adenine C-nucleoside (GS-5734) for the treatment of Ebola and emerging viruses. J Med Chem. 2017;60(5):1648-1661. doi:10.1021/acs.jmedchem.6b01594
  19. Agostini ML, Andres EL, Sims AC, et al. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. mBio. 2018;9(2). doi:10.1128/mBio.00221-18
  20. Jordan PC, Liu C, Raynaud P, et al. Initiation, extension, and termination of RNA synthesis by a paramyxovirus polymerase. PLoS Pathog. 2018;14(2):e1006889. doi:10.1371/journal.ppat.1006889
  21. Lo MK, Feldmann F, Gary JM, et al. Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge. Sci Transl Med. 2019;11(494). doi:10.1126/scitranslmed.aau9242
  22. Mulangu S, Dodd LE, Davey RT Jr, et al. A randomized, controlled trial of Ebola virus disease therapeutics. N Engl J Med. 2019;381(24):2293-2303. doi:10.1056/NEJMoa1910993
  23. Tchesnokov EP, Feng JY, Porter DP, Götte M. Mechanism of inhibition of Ebola virus RNA-dependent RNA polymerase by remdesivir. Viruses. 2019;11(4). doi:10.3390/v11040326
  24. McMullan LK, Flint M, Chakrabarti A, et al. Characterisation of infectious Ebola virus from the ongoing outbreak to guide response activities in the Democratic Republic of the Congo: a phylogenetic and in vitro analysis. Lancet Infect Dis. 2019;19(9):1023-1032. doi:10.1016/s1473-3099(19)30291-9
  25. Brown AJ, Won JJ, Graham RL, et al. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res. 2019;169:104541. doi:10.1016/j.antiviral.2019.104541
  26. Koplon S. $37.5 Million Grant will Address Research of High-Priority Infections. University of Alabama at Birmingham website. https://www.uab.edu/news/health/item/10307-37-5-million-grant-will-address-research-of-high-priority-infections.  Accessed July 22, 2020.
  27. Mehellou Y, Rattan HS, Balzarini J. The ProTide prodrug technology: from the concept to the clinic. J Med Chem. 2018;61(6):2211-2226. doi:10.1021/acs.jmedchem.7b00734
  28. Grein J, Ohmagari N, Shin D, et al. Compassionate use of remdesivir for patients with severe COVID-19. N Engl J Med. 2020;382(24):2327-2336. doi:10.1056/NEJMoa2007016
  29. Biotechnology Innovation Association. Clinical Development Success Rates 2006-2015. https://www.bio.org/sites/default/files/legacy/bioorg/docs/Clinical%20Development%20Success%20Rates%202006-2015%20-%20BIO,%20Biomedtracker,%20Amplion%202016.pdf.  Published 2016.
  30. Dyer O. Two Ebola treatments halve deaths in trial in DRC outbreak. BMJ. 2019;366:l5140. doi:10.1136/bmj.l5140
  31. Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395(10236):1569-1578. doi:10.1016/s0140-6736(20)31022-9
  32. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of COVID-19 - preliminary report. N Engl J Med. 2020. doi:10.1056/NEJMoa2007764
  33. Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization for Potential COVID-19 Treatment. U.S. Food and Drug Administration website. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-potential-covid-19-treatment.  Accessed July 22, 2020. Published 2020.
  34. Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with COVID-19 - preliminary report. N Engl J Med. 2020. doi:10.1056/NEJMoa2021436
  35. Knowledge Ecology International (KEI). Other Transaction Agreements: Government Contracts That May Eliminate Protections for the Public on Pricing, Access and Competition, Including in Connection with COVID-19. KEI Briefing Note 2020:3 June 24, 2020. https://www.keionline.org/wp-content/uploads/KEI-Briefing-OTA-24June2020.pdf. Published 2020.
  36. Contract Data Reports for FPDS Users. U.S. General Services Administration Federal Government website.  https://beta.sam.gov/awards/85565339%2BAWARD?keywords=W911QY1690001&sort=-relevance&index=&is_active=true&page=2.  Accessed July 22, 2020.
  37. Galkina Cleary E, Beierlein JM, Khanuja NS, McNamee LM, Ledley FD. Contribution of NIH funding to new drug approvals 2010-2016. Proc Natl Acad Sci U S A. 2018;115(10):2329-2334. doi:10.1073/pnas.1715368115
  38. Nayak RK, Avorn J, Kesselheim AS. Public sector financial support for late stage discovery of new drugs in the United States: cohort study. BMJ. 2019;367:l5766. doi:10.1136/bmj.l5766
  39. Chakma J, Sun GH, Steinberg JD, Sammut SM, Jagsi R. Asia's ascent--global trends in biomedical R&D expenditures. N Engl J Med. 2014;370(1):3-6. doi:10.1056/NEJMp1311068
  40. 40. Association of American Universities (AAU). Basic Scientific and Engineering Research at U.S. Universities. AAU; 2015. https://www.aau.edu/node/10671.    Accessed July 22, 2020.
  41. Young R, Bekele T, Gunn A, et al. Developing new health technologies for neglected diseases: a pipeline portfolio review and cost model. Gates Open Res. 2018;2:23. doi:10.12688/gatesopenres.12817.2
  42. Azoulay P, Zivin JSG, Li D, Sampat BN. Public R&D Investments and Private-Sector Patenting: Evidence from NIH Funding Rules. https://www.nber.org/papers/w20889.pdf. Published 2015.
  43. Gilead Sciences Statement on Request to Rescind Remdesivir Orphan Drug Designation. Gilead Sciences website. https://www.gilead.com/news-and-press/company-statements/gilead-sciences-statement-on-request-to-rescind-remdesivir-orphan-drug-designation.  Accessed July 22, 2020. Published 2020.
  44. Hill A, Wang J, Levi J, Heath K, Fortunak J. Minimum costs to manufacture new treatments for COVID-19. J Virus Erad. 2020;6(2):61-69. doi:10.1016/s2055-6640(20)30018-2
  45. Silverman E. Gilead Signs Licenses for Generic Companies to Make and Sell Remdesivir in 127 Countries. STAT. 2020. https://www.statnews.com/pharmalot/2020/05/12/gilead-generics-remdesivir-covid19-coronavirus-licenses/.  Accessed July 22, 2020.
  46. Sternlicht A. Entire Stockpile of Coronavirus Treatment Remdesivir Donated to Government, Says CEO. Forbes. May 3, 2020. https://www.forbes.com/sites/alexandrasternlicht/2020/05/03/entire-stockpile-of-coronavirus-treatment-remdesivir-donated-to-government-says-ceo/#4e6b548725fb.  Accessed July 22, 2020.
  47. An Open Letter from Daniel O’Day, Chairman & CEO, Gilead Sciences. Gilead Sciences  website. https://www.gilead.com/news-and-press/press-room/press-releases/2020/6/an-open-letter-from-daniel-oday-chairman--ceo-gilead-sciences.  Accessed July 22, 2020. Published 2020.
  48. Mitra AK, Cavale S. India’s Cipla Prices its Generic Remdesivir at $53.34 Per Vial, Below Rivals. Reuters.  July 8, 2020. https://www.reuters.com/article/us-health-coronavirus-cipla/indias-cipla-prices-its-generic-remdesivir-at-53-34-per-vial-below-rivals-idUSKBN2492Q3.  Accessed July 22, 2020.
  49. Trump Administration Secures New Supplies of Remdesivir for the United States. U.S. Department of Health & Human Services website. https://www.hhs.gov/about/news/2020/06/29/trump-administration-secures-new-supplies-remdesivir-united-states.html.  Accessed July 22, 2020. Published 2020.
  50. World Health Organization Regional Office for South-East Asia. Equity in Access to Public Health, Report and Documentation of the Technical Discussions Held in Conjunction with the 37th Meeting of CCPDM New Delhi, August 31, 2000. New Delhi: WHO; 2000.
  51. Surgo Foundation. Bringing Greater Precision to the COVID-19 Response. Surgo Foundation; 2020.
  52. Jamison DT, Summers LH, Alleyne G, et al. Global health 2035: a world converging within a generation. Lancet. 2013;382(9908):1898-1955. doi:10.1016/s0140-6736(13)62105-4
  53. Moon S, Røttingen JA, Frenk J. Global public goods for health: weaknesses and opportunities in the global health system. Health Econ Policy Law. 2017;12(2):195-205. doi:10.1017/s1744133116000451
  54. Mazzucato M, Li HL, Darzi A. Is it time to nationalise the pharmaceutical industry? BMJ. 2020;368:m769. doi:10.1136/bmj.m769
  55. Bozeman B. Public value science. Issues Sci Technol. 2020;36(4):34-41.
  56. Sarewitz D. The science policy we deserve. Issues Sci Technol. 2020;36(4):20-24.
  57. McGuigan C, Cahard D, Sheeka HM, De Clercq E, Balzarini J. Aryl phosphoramidate derivatives of d4T have improved anti-HIV efficacy in tissue culture and may act by the generation of a novel intracellular metabolite. J Med Chem. 1996;39(8):1748-1753. doi:10.1021/jm950605j
  58. Roy V. The Financialization of a Cure: A Political Economy of Biomedical Innovation, Pricing and Public Health. https://pdfs.semanticscholar.org/77c2/90878829e0e6d31d6dcc1b5a6b6fd132c449.pdf. Published 2017.
  • Receive Date: 04 June 2020
  • Revise Date: 19 August 2020
  • Accept Date: 22 August 2020
  • First Publish Date: 01 May 2022