Open-label use of an aliphatic polyamine immunomodulator in patients hospitalized with COVID-19

Article Details

Authors
Sergey V Efimov, Natallia V Matsiyeuskaya, Olga V Boytsova, Luydmila Yu Akhieva, Elena V Kuntsevich, Anastasia A Troshina, Elena I Kvasova, Anton A Tikhonov, Nadezhda F Khomyakova, Francisco Harrison, Jean-François Rossi, Timothy C Hardman

Article Type
Original Research

DOI
10.7573/dic.2022-1-1

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Abstract

Background: Evidence-based therapies used to treat coronavirus disease (COVID-19) remain limited. Azoximer bromide (AZB; Polyoxidonium®) is an immunomodulating molecule frequently used in the Russian Federation. It offers demonstrable therapeutic benefit in upper respiratory tract infections. This study evaluated the safety and efficacy of AZB when used in combination with standard of care treatment in patients hospitalized with COVID-19.

Methods: Hospitalized patients with COVID-19 (n=81; nine sites) received AZB 12 mg intravenously once daily for 3 days then intramuscularly every other day until day 17. The primary endpoint included clinical status at day 15 versus baseline. Historical control data of 100 patients from a randomized, controlled, open-label trial conducted in China were included to serve as a direct control group.

Results: Notable clinical improvement, assessed by seven-point ordinal scale (OS) score and National Early Warning Score, was observed. Mean duration of hospitalization was 19.3 days. Indicators of pneumonia and lung function showed gradual recovery to normalization. No patients died but, by day 28, one patient still required respiratory support; this patient died on day 34. A higher proportion of patients receiving AZB required invasive or non-invasive ventilation (OS 5 or 6) at baseline compared with the historical control group. Improvement in mean OS score by day 14/15 was not notable in the control group (OS 3.99–3.87) but was clear in the AZB group (OS 4.36–2.90). Mean duration of hospitalization was similar in the control group (16.0 days); however, day 28 mortality was higher, at 25.0% (n=25).

Conclusion: AZB combined with standard of care was safe and well tolerated. An apparent clinical improvement could not be fully evaluated due to the lack of a direct control group; further assessment of AZB for the treatment of COVID-19 in a randomized, placebo-controlled study is warranted.

Keywords: azoximer bromide, COVID-19, clinical improvement, exploratory research, Polyoxidonium®.

Citation: Efimov SV, Matsiyeuskaya NV, Boytsova OV, Akhieva LY, Kuntsevich EV, Troshina AA, Kvasova EI, Tikhonov AA, Khomyakova NF, Harrison F, Rossi JF, Hardman TC. Open-label use of an aliphatic polyamine immunomodulator in patients hospitalized with COVID-19. Drugs Context. 2022;11:2022-1-1. https://doi.org/10.7573/dic.2022-1-1

Contributions: All authors contributed to the study concept and design. SVE, NVM, OVB, LYA, EVK, AAT and EIK enrolled the patients and collected the data. NFK wrote the protocol. AAT and FH managed data collection, monitoring and clean-up. AAT, FH and J-FR analysed the data. TCH, AAT, FH and J-FR wrote the manuscript. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: AAT and NFK are employees of NPO Petrovax Pharm LLC. FH and TCH work for organizations contracted by NPO Petrovax Pharm. J-FR is a consultant for NPO Petrovax Pharm. All other authors do not have any conflicting or competing interests. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2022/02/dic.2022-1-1-COI.pdf

Acknowledgements: We are grateful to Nikolay S Dodonov, Tatyana A Kireeva, Altana V Mikhakhanova, Ekaterina I Zvorykina, Yulia S Karpova, Natalia V Komissarova, Elena N Markova, Ilya N Mishchenko, Timur R Zagidullin, Anna N Kochanova, Liana S Badalyan, Karina I Khambalova and Vasiliy V Gaevskiy for their excellent technical assistance. Medical writing support was provided by Madeleine Parker of Niche Science and Technology Ltd, Richmond-upon-Thames, Surrey, UK.

Funding declaration: This study was designed, funded and managed by NPO Petrovax Pharm LLC (Moscow, Russia).

Copyright: Copyright © 2022 Efimov SV, Matsiyeuskaya NV, Boytsova OV, Akhieva LY, Kuntsevich EV, Troshina AA, Kvasova EI, Tikhonov AA, Khomyakova NF, Harrison F, Rossi JF, Hardman TC. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2022 Efimov SV, Matsiyeuskaya NV, Boytsova OV, Akhieva LY, Kuntsevich EV, Troshina AA, Kvasova EI, Tikhonov AA, Khomyakova NF, Harrison F, Rossi JF, Hardman TC. https://doi.org/10.7573/dic.2022-1-1. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/open-label-use-of-an-aliphatic-polyamine-immunomodulator-in-patients-hospitalized-with-covid-19

Correspondence: Tim Hardman, 26 Bardolph Road, Richmond, TW9 2LH, UK. Email: tim.hardman@niche.org.uk

Provenance: Invited; externally peer reviewed.

Submitted: 4 January 2022; Accepted: 24 January 2022; Publication date: 3 March 2022.

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