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  • 1 Gyógyszerkémiai Kutatócsoport, Természettudományi Kutatóközpont, , Budapest, Magyarország; Medicinal Chemistry Research Group, Research Centre for Natural Sciences, , Budapest, Hungary
  • | 2 Magyar Koronavírus-kutatási Akciócsoport; Hungarian Coronavirus Research Task Force
Open access

Összefoglaló. Egészen az ezredfordulóig a gyógyszeripari kutatás-fejlesztés világszerte hagyományosan nagyvállalati keretek között folyt. Az elmúlt évtizedekben azonban ebben a szegmensben jelentős átrendeződések tapasztalhatók, ugyanis a korai kutatási és fejlesztési projektek sok esetben már az egyetemi-akadémiai, illetve kkv-szektorból indulnak. A szervezeti keretek mellett a fejlesztések szakmai tartalma is változott, a hagyományos kismolekulás gyógyszerek mellett egyre meghatározóbb szerep jut a biológiai terápiáknak, valamint a hatóanyagok fejlesztése mára összekapcsolódott a releváns diagnosztikumok fejlesztésével. A projektek finanszírozásában is fontos változások történtek, egyre jelentősebb szerep jut az állami KFI finanszírozásnak és a (kockázati) tőkebefektetéseknek. A gyógyszeripari K+F szakmai, szervezeti és finanszírozási kereteinek változása jelentősen felértékelte és szélesítette a korábban is meglévő akadémiai-ipari kapcsolatokat. Az együttműködések fontos szerepet játszanak a COVID–19 járványra adott válaszokban is, amit a magyar egyetemek, kutatóintézetek, kis- és középvállalatok, valamint gyógyszeripari nagyvállalatok részvételével indult kutatások igazolnak.

Summary. Until the turn of the millennium, pharmaceutical research and development worldwide had traditionally taken place in pharmaceutical companies. In recent decades, however, significant rearrangements have been witnessed, as early-stage research and development projects often start at the universities or the academic and SME sectors. In addition to the organizational framework, the professional content has also changed: in addition to traditional small molecule drugs, biological therapies are playing an increasingly important role, and the development of active ingredients is now linked to the development of relevant diagnostics. Important changes have also taken place in the financing of projects, with public RDI financing and (venture) capital investments playing an increasing role. Changes in the professional, organizational and funding frameworks for pharmaceutical R&D have significantly enhanced and broadened existing academic-industrial relations. Collaborations also play an important role in the responses to the COVID-19 epidemic, as evidenced by research involving Hungarian universities, research institutes, small and medium-sized enterprises, and large pharmaceutical companies. The first example is a collaboration of an academic research group and a spin-off company formed from this environment. Researchers of the Eötvös University (ELTE) and others working at the Research Centre for Natural Sciences (RCNS) applied phage display technology to discover new protease inhibitors. They established EvolVeritas Ltd, a spin-off company developing high affinity and high specificity inhibitors of the TMPRSS2 protease that is involved in the SARS-CoV-2 viral entry to host cells. In a parallel research program, the same consortium is working on new inhibitors of the MASP2 protease contributing to the coronavirus mediated activation of innate immunity, particularly the complement system. This latter approach would result in the effective control of microthrombosis events associated with serious COVID-19 infections. Both of the approaches are in the early preclinical phase and further investment would be needed to push these projects into clinical testing. The second example is a collaboration between an academic research group and an SME to reposition of azelastine, an approved antihistamine drug that was found to be effective in blocking SARS-CoV-2 mediated pathogenesis. After successful preclinical studies, the partners have now initiated clinical trials to demonstrate the efficacy of azelastine nasal drops in the prevention and treatment of COVID-19 infections. The third example is a collaboration of academic research groups, a SME and a pharmaceutical company. This consortium develops an antibody-like fusion protein therapeutics that can neutralize the SARS-CoV-2 virus. One component of the ACE2-Fc fusion protein is the relevant portion of angiotensin-converting enzyme 2 (ACE2) produced by recombinant technologies, which binds to the spike protein of the pathogen. The virus thus binds to the fusion protein instead of the ACE2 receptors in human cells. Another component is responsible for the long half-life of IgG, the so-called Fc region. The consortium confirmed that the ACE2-Fc fusion protein inhibits SARS-CoV-2 infection in cell culture, and prevents disease in experimental animals. Preclinical development and the preparation of the core documentation is ongoing, which will soon be submitted to the European Medicines Agency (EMA) to initiate clinical trials. The final example is a joint development project that involved a research group, an SME and two pharmaceutical companies. The objective of this program is process development and pharmaceutical formulation of favipiravir, a broad-spectrum antiviral with a treatment potential against COVID-19. The consortium completed the process development of the active pharmaceutical ingredient (API) and developed finished dosage formulations available for clinical testing. Clinical trials are ongoing that aim investigating safety and efficacy of favipiravir in COVID-19 infected patients. All of the examples described here demonstrate the power of collaborations that helped the participants to give diverse and effective responses to the unprecedented pandemic challenge of COVID-19. We believe that these experiences would encourage the members of the academic and industry community to formulate further collaborations to tackle the unmet medical need in our societies.

  • 1

    Furuta, Y., Komeno, T., & Nakamura, T. (2017) Favipiravir (T-705), a broad spectrum inhibitor of viral RNA polymerase. Proceedings of the Japan Academy. Series B, Physical and biological sciences, Vol. 93. No. 7. pp. 449–463. https://doi.org/10.2183/pjab.93.027

  • 2

    Guy, R. K., DiPaola, R. S., Romanelli, F., & Dutch, R. E. (2020) Rapid repurposing of drugs for COVID-19. Science (New York, N.Y.) Vol. 368. No. 6493. pp. 829–830.

  • 3

    Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens T. S., Herrler, G., Wu, N.-H., Nitsche, A., & Müller, M. A. (2020) SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, Vol. 181. No. 2. pp. 271–280.

  • 4

    Khanna, I. (2012) Drug discovery in pharmaceutical industry: productivity challenges and trends. Drug Discov Today, Vol. 17. No. 19–20. pp. 1088–1102.

  • 5

    Kneller, R. (2010) The importance of new companies for drug discovery: origins of a decade of new drugs. Nat Rev Drug Discov. Vol. 9. No. 11. pp. 867–882.

  • 6

    Konrat, R., Papp, H., Szijártó, V., Gesell, T., Nagy, G., Madai, M., ... Nagy, E. (2020) The Anti-histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits SARS-CoV-2 Infection in Reconstituted Human Nasal Tissue In Vitro. bioRxiv. https://doi.org/10.1101/2020.09.15.296228. (This article is a preprint and has not been certified by peer review)

  • 7

    Lei, C., Qian, K., Li, T., Zhang, S., Fu, W., Ding, M., & Hu, S. (2020) Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig. Nature Communications, 11, Article no. 2070. https://doi.org/10.1038/s41467-020-16048-4

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    Lincker, H., Ziogas, C., Carr, M., Porta, N., Eichler, H.-G. (2014) Regulatory watch: where do new medicines originate from in the EU? Nat Rev Drug Discov. Vol. 13. No. 2. pp. 92–93.

  • 9

    Mullard, A. (2018) FDA drug approvals. Nat Rev Drug Discov. Vol. 18. No. 2. 85–89.

  • 10

    Patridge, E. V., Gareiss, P. C., Kinch, M. S., Hoyer, D. W. (2015) An analysis of original research contributions toward FDA-approved drugs. Drug Discov Today, Vol. 20. No. 10. pp. 1182–1187.

  • 11

    Schuhmacher, A., Gassmann, O., Hinder, M. (2016) Changing R&D models in research-based pharmaceutical companies. J Transl Med. Vol. 14. Article no. 105.

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2020  
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Scientia et Securitas
Language Hungarian
English
Size A4
Year of
Foundation
2020
Publication
Programme
2020 Volume 1
Volumes
per Year
1
Issues
per Year
4
Founder Academic Council of Home Affairs and
Association of Hungarian PhD and DLA Candidates
Founder's
Address
H-2090 Remeteszőlős, Hungary, Nagykovácsi út 3.
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Publisher Akadémiai Kiadó
Publisher's
Address
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Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN ISSN 2732-2688

Editor-in-Chief:

  • Tamás NÉMETH 
    (Institute for Soil Sciences and Agricultural Chemistry, Centre for Agricultural Research
    Budapest, Hungary)

Managing Editor:

  • István SABJANICS (Ministry of Interior, Budapest, Hungary)

Editorial Board:

  • Melinda KOVÁCS (Szent István University Kaposvár Campus)Á
  • Miklós MARÓTH (Eötvös Loránd Research Network)
  • Charaf HASSAN (Budapest University of Technology and Economics)
  • Zoltán GYŐRI (Hungaricum Committee)
  • József HALLER (University of Public Service)
  • Attila ASZÓDI (Budapest University of Technology and Economics)
  • Zoltán BIRKNER (National Research, Development and Innovation Office)
  • Tamás DEZSŐ (Migration Research Institute)
  • Imre DOBÁK (University of Public Service)
  • András KOLTAY (University of Public Service)
  • Gábor KOVÁCS (University of Public Service)
  • József PALLO (University of Public Service)
  • Marcell Gyula GÁSPÁR (University of Miskolc)
  • Judit MÓGOR (Ministry of Interior National Directorate General for Disaster Management)
  • István SABJANICS (Ministry of Interior)
  • Péter SZABÓ (Hungarian University of Agriculture and Life Sciences (MATE))
  • Miklós SZÓCSKA (Semmelweis University)
  • János JÓZSA (Budapest University of Technology and Economics)
  • Valéria CSÉPE (Research Centre for Natural Sciences, Brain Imaging Centre)