Abstract: Clinical Infectious Diseases
BRIEF REPORT
AVIFAVIR for Treatment of Patients
With Moderate Coronavirus Disease
2019 (COVID-19): Interim Results of
a Phase II/III Multicenter Randomized
Clinical Trial
Andrey A. Ivashchenko,1 Kirill A. Dmitriev,2 Natalia V. Vostokova,3
Valeria N. Azarova,3 Andrew A. Blinow,4 Alina N. Egorova,3 Ivan G. Gordeev,5
Alexey P. Ilin,6 Ruben N. Karapetian,7 Dmitry V. Kravchenko,6 Nikita V. Lomakin,8
Elena A. Merkulova,3 Natalia A. Papazova,9 Elena P. Pavlikova,10
Nikolay P. Savchuk,11 Elena N. Simakina,12 Tagir A. Sitdekov,2
Elena A. Smolyarchuk,13 Elena G. Tikhomolova,14 Elena V. Yakubova,4 and
Alexandre V. Ivachtchenko11
ChemRar High-Tech Center, Khimki, Moscow region, Russian Federation, 2Russian Direct
Investment Fund, Moscow, Russian Federation, 3IPHARMA LLC, Skolkovo Innovative Centre,
Moscow, Russian Federation, 4Chromis LLC, Skolkovo Innovative Centre, Moscow, Russian
Federation, 5City Clinical Hospital n.a. O.M. Filatov, Moscow, Russian Federation, 6Department
of Chemistry and Technology, Chemical Diversity Research Institute, Khimki, Moscow region,
Russian Federation, 7Department of Biology, Chemical Diversity Research Institute, Khimki,
Moscow region, Russian Federation, 8Central Clinical Hospital with Polyclinic, Moscow,
Russian Federation, 9Department of Finished Dosage Forms, Chemical Diversity Research
Institute, Khimki, Moscow region, Russian Federation, 10Moscow State University n.a. M. V.
Lomonosov, Moscow, Russian Federation, 11Chemical Diversity Research Institute, Khimki,
Moscow region, Russian Federation, 12Clinical Hospital No.1, Smolensk, Russian Federation,
13
First Moscow State Medical University n.a. I.M. Sechenov, Moscow, Russian Federation, and
14
Infectious clinical hospital No. 2, Nizhny Novgorod, Russian Federation
1
In May 2020 the Russian Ministry of Health granted fasttrack marketing authorization to RNA polymerase inhibitor
AVIFAVIR (favipiravir) for the treatment of COVID-19 patients. In the pilot stage of Phase II/III clinical trial, AVIFAVIR
enabled SARS-CoV-2 viral clearance in 62.5% of patients within
4 days, and was safe and well-tolerated.
Clinical Trials Registration. NCT04434248.
Keywords.
AVIFAVIR;
favipiravir;
COVID-19;
SARS-CoV-2.
The pandemic of the novel coronavirus infection (COVID-19)
represents an unprecedented disaster for healthcare providers
and economy worldwide. The urgent requirement for effective
treatments has sparked an intense effort on the part of the pharmaceutical industry and shifted drug development to a new
scale of commitment and collaboration.
Received 26 June 2020; editorial decision 5 August 2020; accepted 6 August 2020; published
online August 9, 2020.
Correspondence: N. V. Vostokova, IPHARMA LLC, Moscow, Russian Federation (nv@ipharma.ru).
Clinical Infectious Diseases® 2021;73(3):531–4
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases
Society of America. This is an Open Access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/
by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any
medium, provided the original work is not altered or transformed in any way, and that the
work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
DOI: 10.1093/cid/ciaa1176
Repositioning of antiviral drugs that could be effective
against SARS-CoV-2 is one of..
{ 'indexed': {'date-parts': [[2024, 4, 8]], 'date-time': '2024-04-08T15:54:09Z', 'timestamp': 1712591649926},
'reference-count': 9,
'publisher': 'Oxford University Press (OUP)',
'issue': '3',
'license': [ { 'start': { 'date-parts': [[2020, 8, 8]],
'date-time': '2020-08-08T00:00:00Z',
'timestamp': 1596844800000},
'content-version': 'vor',
'delay-in-days': 0,
'URL': 'http://creativecommons.org/licenses/by-nc-nd/4.0/'}],
'funder': [ {'name': 'AVIFAVIR', 'award': ['2020724139']},
{'name': 'Russian Direct Investment Fund', 'award': ['2020724142', '2020724139']},
{'name': 'Trade of the Russian Federation and the Skolkovo Innovation Center'}],
'content-domain': {'domain': [], 'crossmark-restriction': False},
'published-print': {'date-parts': [[2021, 8, 2]]},
'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:p>In May 2020 the Russian Ministry of Health granted fast-track '
'marketing authorization to RNA polymerase inhibitor AVIFAVIR (favipiravir) for the treatment '
'of COVID-19 patients. In the pilot stage of Phase II/III clinical trial, AVIFAVIR enabled '
'SARS-CoV-2 viral clearance in 62.5% of patients within 4 days, and was safe and '
'well-tolerated.</jats:p>\n'
' <jats:p>Clinical Trials Registration. NCT04434248.</jats:p>',
'DOI': '10.1093/cid/ciaa1176',
'type': 'journal-article',
'created': {'date-parts': [[2020, 8, 7]], 'date-time': '2020-08-07T03:41:52Z', 'timestamp': 1596771712000},
'page': '531-534',
'source': 'Crossref',
'is-referenced-by-count': 161,
'title': 'AVIFAVIR for Treatment of Patients With Moderate Coronavirus Disease 2019 (COVID-19): Interim '
'Results of a Phase II/III Multicenter Randomized Clinical Trial',
'prefix': '10.1093',
'volume': '73',
'author': [ { 'given': 'Andrey A',
'family': 'Ivashchenko',
'sequence': 'first',
'affiliation': [ { 'name': 'ChemRar High-Tech Center, Khimki, Moscow region, Russian '
'Federation'}]},
{ 'given': 'Kirill A',
'family': 'Dmitriev',
'sequence': 'additional',
'affiliation': [{'name': 'Russian Direct Investment Fund, Moscow, Russian Federation'}]},
{ 'given': 'Natalia V',
'family': 'Vostokova',
'sequence': 'additional',
'affiliation': [ { 'name': 'IPHARMA LLC, Skolkovo Innovative Centre, Moscow, Russian '
'Federation'}]},
{ 'given': 'Valeria N',
'family': 'Azarova',
'sequence': 'additional',
'affiliation': [ { 'name': 'IPHARMA LLC, Skolkovo Innovative Centre, Moscow, Russian '
'Federation'}]},
{ 'given': 'Andrew A',
'family': 'Blinow',
'sequence': 'additional',
'affiliation': [ { 'name': 'Chromis LLC, Skolkovo Innovative Centre, Moscow, Russian '
'Federation'}]},
{ 'given': 'Alina N',
'family': 'Egorova',
'sequence': 'additional',
'affiliation': [ { 'name': 'IPHARMA LLC, Skolkovo Innovative Centre, Moscow, Russian '
'Federation'}]},
{ 'given': 'Ivan G',
'family': 'Gordeev',
'sequence': 'additional',
'affiliation': [ { 'name': 'City Clinical Hospital n.a. O.M. Filatov, Moscow, Russian '
'Federation'}]},
{ 'given': 'Alexey P',
'family': 'Ilin',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Chemistry and Technology, Chemical Diversity '
'Research Institute, Khimki, Moscow region, Russian Federation'}]},
{ 'given': 'Ruben N',
'family': 'Karapetian',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Biology, Chemical Diversity Research Institute, '
'Khimki, Moscow region, Russian Federation'}]},
{ 'given': 'Dmitry V',
'family': 'Kravchenko',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Chemistry and Technology, Chemical Diversity '
'Research Institute, Khimki, Moscow region, Russian Federation'}]},
{ 'given': 'Nikita V',
'family': 'Lomakin',
'sequence': 'additional',
'affiliation': [ { 'name': 'Central Clinical Hospital with Polyclinic, Moscow, Russian '
'Federation'}]},
{ 'given': 'Elena A',
'family': 'Merkulova',
'sequence': 'additional',
'affiliation': [ { 'name': 'IPHARMA LLC, Skolkovo Innovative Centre, Moscow, Russian '
'Federation'}]},
{ 'given': 'Natalia A',
'family': 'Papazova',
'sequence': 'additional',
'affiliation': [ { 'name': 'Department of Finished Dosage Forms, Chemical Diversity Research '
'Institute, Khimki, Moscow region, Russian Federation'}]},
{ 'given': 'Elena P',
'family': 'Pavlikova',
'sequence': 'additional',
'affiliation': [ { 'name': 'Moscow State University n.a. M. V. Lomonosov, Moscow, Russian '
'Federation'}]},
{ 'given': 'Nikolay P',
'family': 'Savchuk',
'sequence': 'additional',
'affiliation': [ { 'name': 'Chemical Diversity Research Institute, Khimki, Moscow region, '
'Russian Federation'}]},
{ 'given': 'Elena N',
'family': 'Simakina',
'sequence': 'additional',
'affiliation': [{'name': 'Clinical Hospital No.1, Smolensk, Russian Federation'}]},
{ 'given': 'Tagir A',
'family': 'Sitdekov',
'sequence': 'additional',
'affiliation': [{'name': 'Russian Direct Investment Fund, Moscow, Russian Federation'}]},
{ 'given': 'Elena A',
'family': 'Smolyarchuk',
'sequence': 'additional',
'affiliation': [ { 'name': 'First Moscow State Medical University n.a. I.M. Sechenov, '
'Moscow, Russian Federation'}]},
{ 'given': 'Elena G',
'family': 'Tikhomolova',
'sequence': 'additional',
'affiliation': [ { 'name': 'Infectious clinical hospital No. 2, Nizhny Novgorod, Russian '
'Federation'}]},
{ 'given': 'Elena V',
'family': 'Yakubova',
'sequence': 'additional',
'affiliation': [ { 'name': 'Chromis LLC, Skolkovo Innovative Centre, Moscow, Russian '
'Federation'}]},
{ 'given': 'Alexandre V',
'family': 'Ivachtchenko',
'sequence': 'additional',
'affiliation': [ { 'name': 'Chemical Diversity Research Institute, Khimki, Moscow region, '
'Russian Federation'}]}],
'member': '286',
'published-online': {'date-parts': [[2020, 8, 9]]},
'reference': [ { 'key': '2021080205021245000_CIT0001',
'doi-asserted-by': 'crossref',
'first-page': '791',
'DOI': '10.3389/fphar.2020.00791',
'article-title': 'Available evidence and ongoing clinical trials of remdesivir: could it '
'be a promising therapeutic option for COVID-19?',
'volume': '11',
'author': 'Sisay',
'year': '2020',
'journal-title': 'Front Pharmacol'},
{ 'key': '2021080205021245000_CIT0002',
'volume-title': 'Avigan Tablet 200 mg. Report on the Deliberation Results. Evaluation and '
'Licensing Division, Pharmaceutical and Food Safety Bureau. Ministry of '
'Health, Labour and Welfare. March 4, 2014'},
{ 'key': '2021080205021245000_CIT0003',
'doi-asserted-by': 'crossref',
'first-page': '269',
'DOI': '10.1038/s41422-020-0282-0',
'article-title': 'Remdesivir and chloroquine effectively inhibit the recently emerged '
'novel coronavirus (2019-nCoV) in vitro',
'volume': '30',
'author': 'Wang',
'year': '2020',
'journal-title': 'Cell Res'},
{ 'key': '2021080205021245000_CIT0004',
'doi-asserted-by': 'crossref',
'DOI': '10.1016/j.eng.2020.03.007',
'article-title': 'Experimental treatment with favipiravir for COVID-19: an open-label '
'control study',
'author': 'Cai',
'year': '2020',
'journal-title': 'Engineering'},
{ 'key': '2021080205021245000_CIT0005',
'volume-title': 'COVID Classification of treatment types',
'author': 'WHO R&D Blueprint COVID 19 Experimental Treatments.',
'year': '2020'},
{ 'key': '2021080205021245000_CIT0006',
'author': 'WHO R&D Blueprint novel Coronavirus COVID-19 Therapeutic Trial Synopsis.'},
{ 'key': '2021080205021245000_CIT0007',
'volume-title': 'Prevention, diagnostics and treatment of a new coronavirus infection '
'(COVID-19), MOH of the Russian Federation',
'author': 'Interim guidelines.'},
{ 'key': '2021080205021245000_CIT0008',
'doi-asserted-by': 'crossref',
'first-page': '859',
'DOI': '10.1002/sim.721',
'article-title': 'Sample size tables for exact single-stage phase II designs',
'volume': '20',
'author': 'A’Hern',
'year': '2001',
'journal-title': 'Stat Med'},
{ 'key': '2021080205021245000_CIT0009',
'doi-asserted-by': 'crossref',
'first-page': '45',
'DOI': '10.1016/S2055-6640(20)30016-9',
'article-title': 'A review of the safety of favipiravir–a potential treatment in the '
'COVID-19 pandemic?',
'volume': '6',
'author': 'Pilkington',
'year': '2020',
'journal-title': 'J Virus Erad'}],
'container-title': 'Clinical Infectious Diseases',
'original-title': [],
'language': 'en',
'link': [ { 'URL': 'http://academic.oup.com/cid/advance-article-pdf/doi/10.1093/cid/ciaa1176/34459516/ciaa1176.pdf',
'content-type': 'application/pdf',
'content-version': 'am',
'intended-application': 'syndication'},
{ 'URL': 'http://academic.oup.com/cid/article-pdf/73/3/531/39508421/ciaa1176.pdf',
'content-type': 'application/pdf',
'content-version': 'vor',
'intended-application': 'syndication'},
{ 'URL': 'http://academic.oup.com/cid/article-pdf/73/3/531/39508421/ciaa1176.pdf',
'content-type': 'unspecified',
'content-version': 'vor',
'intended-application': 'similarity-checking'}],
'deposited': { 'date-parts': [[2021, 8, 2]],
'date-time': '2021-08-02T05:03:40Z',
'timestamp': 1627880620000},
'score': 1,
'resource': {'primary': {'URL': 'https://academic.oup.com/cid/article/73/3/531/5890024'}},
'subtitle': [],
'short-title': [],
'issued': {'date-parts': [[2020, 8, 9]]},
'references-count': 9,
'journal-issue': { 'issue': '3',
'published-online': {'date-parts': [[2020, 8, 9]]},
'published-print': {'date-parts': [[2021, 8, 2]]}},
'URL': 'http://dx.doi.org/10.1093/cid/ciaa1176',
'relation': { 'has-preprint': [ { 'id-type': 'doi',
'id': '10.1101/2020.07.26.20154724',
'asserted-by': 'object'}]},
'ISSN': ['1058-4838', '1537-6591'],
'subject': ['Infectious Diseases', 'Microbiology (medical)'],
'published-other': {'date-parts': [[2021, 8, 1]]},
'published': {'date-parts': [[2020, 8, 9]]}}