The interim analysis of a multi-center, double-blind, randomised, placebo-controlled trial to assess the efficacy and safety of AMIZON® MAX manufactured by JSC Farmak in the treatment of moderate-severity COVID-19 patients was carried out as of mid-January 2021. The study of the medicinal product has been conducted in combination with standard treatment of coronavirus patients. The trial is currently undergoing and additional patients are being recruited.
Olha Holubovska, Doctor of Medical Sciences, Professor, and Alla Mironenko, Doctor of Medical Sciences, Professor, have been involved in the trial as a main researcher and a person responsible for virological analysis, respectively.
Dr. Lutz Müller, a German regulatory consultant involved in Amazon clinical study in Ukraine, states the following in his open letter regarding clinical trial:
“The study has been planned and conducted in accordance with the requirements of ICH, the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, as determined by ICH E6 (R2) Good Clinical Practice. The study approval by the competent ethics committees and local regulatory authorities has been obtained prior to the clinical study.
The study design meets modern international requirements for key aspects of phase 3 clinical trials.
An interim analysis of the clinical study has been conducted by an independent data monitoring committee to ensure that it has been blind for the organizers, in accordance with the GCP requirements prescribed by ICH E9 Statistical Principles for Clinical Trials.
Our company has advised the study sponsor on the study design, international requirements for the regulation of clinical study and ICH E6 (R2) guidelines. Another well-known German research organization has been responsible for statistical planning, development and maintenance of records, as well as data management.”
The primary endpoint was the time from day of randomization to the improvement of the patient’s condition by at least two points according to the severity rating (SR) scale (modified WHO Scale) in days:
The main provisions of the record of this clinical study are published on the website Search of: enisamium | Covid19 – List Results – ClinicalTrials.gov.
Interim results of phase 3 analysis of Amizon (enisamium iodide) clinical study have demonstrated its efficacy in patients who have required non-invasive oxygen support to improve blood oxygen saturation (SR 4), accelerating the significant improvement in their state by two points of in the severity rating scale (SR 6) on average by 2.8 days (median – 2 days); differences between group Y (11.1 days, n = 38) and X (13.9 days, n = 39) in patients of SR 4 have been statistically significant (p = 0.0259).
In mild COVID-19 patients (SR 5), in whom the rate of oxygen saturation does not exceed normal values, significant differences between groups X (n = 146) and Y (n = 150) have not been found, what may be associated with lower viral load in study subjects with those in patients with more severe course of the disease (SR 4).
Therefore, permission from the regulatory authority to continue clinical study of Amizon in patients whose station meets the criteria of SR 4 has been obtained.
In the 1st quarter of 2020, antiviral study of enisamium iodide, the active substance of Amizon, has been conducted at the Frankfurt Institute of Medical Virology at Goethe University (Germany). Enisamium has been shown to have antiviral activity against SARS-CoV-2 coronavirus.
The scientists from the Universities of Oxford and Cambridge (UK) have discovered the mechanism of action of enisamium: antiviral effect is due to the direct inhibitory action of its active metabolite VR17-04 on the viral RNA-dependent RNA polymerase of the coronavirus SARS-CoV-2. The active metabolite of enisamium interacts with the active site of viral RNA-dependent RNA polymerase.
Based on the above results, the direct RNA-dependent RNA polymerase inhibitor SARS-CoV-2 Amizon has been admitted to phase 3 clinical study to assess its safety and efficacy in the treatment of patients with COVID-19, the severity of which corresponds to SR 4, in combination with basic therapy (see above); this study has been started in the 2nd quarter and continued in the 4th quarter of last year. This clinical trial is currently ongoing.
The results of the study of the mechanism of action and intermediate results of phase 3 clinical trials are included in the article ‘Enisamium is an inhibitor of the 1 SARS-CoV-2 RNA polymerase and shows improvement of recovery in COVID-19 patients in an interim analysis of a clinical trial’ (authors: O. Holubovska, D. Bojkova, S. Elli, M. Bechtel, D. Boltz, M. Muzzio, X. Peng, F. Sala, C. Cosentino, A. Mironenko, J. Milde, Y. Lebed, H. Stammer, A. Goy, M. Guerrini, L. Mueller, J. Cinatl, V. Margitich, Aartjan J.W. te Velthuis), a pre-print of which can be found at https://www.medrxiv.org/content/10.1101/2021.01.05.21249237v1
The compound has been developed by scientists of the Institute of Pharmacology and Toxicology of the National Academy of Medical Sciences of Ukraine and implemented at manufacturing facilities of JSC Farmak. In 1997 Amizon® has been registered in Ukraine as a non-narcotic analgesic.
In 2005, Corresponding Member of the NAS and NAMS of Ukraine, RAMS, Professor, Doctor of Medical Sciences, A.F. Frolov was the first to demonstrate the antiviral effect of enisamium against influenza virus in in vitro experiments (in the laboratory).
In 2008 JSC Farmak has started the global non-clinical and clinical development of enisamium iodide as an antiviral medicinal product against influenza.
The non-clinical program, which included a full range of pharmacological, pharmacokinetic and toxicological studies, has been performed in well-known research institutes and laboratories in Germany, the United Kingdom, the Czech Republic, the Netherlands, Switzerland, Hungary and the United States.
To date, it has been found that enisamium exhibits a broad-spectrum antiviral effect: Against influenza virus types A (H1N1, H3N2, including highly pathogenic strains H5N1 and H7N9), and B; pandemic beta-coronavirus SARS-CoV-2; seasonal alpha-coronavirus NL63; respiratory syncytial virus.
Phase 1 clinical study of Amizon have been conducted in Germany and Austria; phase 3 has been conducted in Russia (Smorodintsev Research Institute of Influenza, St. Petersburg) in influenza and SARS patients (2010).
As of today, Amizon has been registered in 11 countries in Eastern Europe and Asia.
Farmak is an international pharmaceutical company headquartered in Kyiv. The Company’s manufacturing facilities are located in Ukraine and Poland. Amizon non-clinical study has been sponsored by Farmak International Holding GmbH (Vienna, Austria), and Phase 3 clinical study has been sponsored by JSC Farmak (Kyiv). Farmak’s main business is the development, manufacturing and marketing of high-quality bioequivalent generics which are manufactured in accordance with GMP.
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