ChemRar Group announces the Russian Avifavir? (INN: favipiravir) drug is effective against various variants of SARS-CoV-2 (coronavirus), including Delta and Omicron, as it affects the highly conservative and mutation-resistant replication systems of RNA virus (RdRp) via three complementary mechanisms, resulting in complete blockade of the viral infection.

In addition, the virus is incapable of developing resistance to favipiravir even with long-term exposure on infected cells, as has been confirmed in clinical trials. This provides Avifavir? with a major advantage not only over highly specific biologics but also over many other similar nucleoside products prone to inducing rapid evolution of resistant clinical variants.

The problem of rapid mutation is particularly typical of RNA viruses, such as SARS-CoV-2 (coronavirus). Most of the mutations are found in the spike protein structure, in particular in two of its key parts that are recognized by the human immune system.

A meta analysis of 23 COVID-19 treatment studies for favipiravir is demonstrating a 47% improvement when favipiravir is used in early treatment of coronavirus. This analysis is available at: https://c19favipiravir.com/meta.html

In June 2020, with the support of the Russian Direct Investment Fund (RDIF, Russia's sovereign wealth fund), ChemRar Group specialists developed and were the first in the world to release Avifavir? (INN: favipiravir), a direct antiviral for COVID-19 treatment, to the Russian and international markets. The product's efficacy has been confirmed in a full-scale clinical trial in Russia involving 460 COVID patients. Avifavir? has been supplied to more than 15 countries around the world.

Clinical trials of Avifavir? have demonstrated its anti-COVID properties, such as alleviating symptoms and cut the duration of the disease by half compared to standard therapy.

In particular:

Avifavir? is demonstrating the best results in COVID treatment when used in the first 3-5 days after first symptoms;

• After the first 4 days of treatment, 65 % of patients on Avifavir? tested negative for coronavirus, twice the rate of the standard treatment group. By day 10, the number of negative patients had reached 90 %;

• In 68 % of patients on Avifavir?, body temperature normalized earlier (on Day 3) compared to the control group (on Day 6).

• Median time to clinical improvement with Avifavir? was 7 days vs. 10 days in the standard treatment group.

In addition, the results of Avifavir? in patients with COVID-19 are being closely monitored in real-world clinical practice. A retrospective review of favipiravir's efficacy and safety is currently under way in 40,000 patients exposed to the product in an outpatient or inpatient setting.

In 2020–2021, potential of favipiravir against coronavirus infection was actively investigated in more than 50 clinical trials involving around 5,000 patients in Russia, Japan, China, India, Thailand, Turkey, Iran, Saudi Arabia, EU countries and Latin America. To date, the PubMed database of international medical and biological literature contains almost 900 peer-reviewed favipiravir-related papers. At least 700 of them were published in the last 1.5 years. These publications speak for the high efficacy and safety of favipiravir against COVID-19.

Elena Yakubova, Medical Director of ChemRar Group, commented:

"Having accumulated extensive experience with Avifavir? in patients infected with COVID both from clinical trials and real-world clinical practice, we see that taking Avifavir? in the first 3–5 days after infection leads to a milder disease in most cases and prevents hospitalization. Over the past 17 months, more than 4 million patients have been treated with favipiravir worldwide. The product was well tolerated with no new adverse events, which confirms the high safety of favipiravir."

To date, vast body of information has been accumulated in the scientific literature on various aspects of the favipiravir pharmacology as the product has been well studied, including its mechanisms of action, activity in vitro and in vivo, clinical efficacy, safety, cost-effectiveness, potential for combination therapy, analytical control methods, etc. A series of clinical trials in 2020-2021 have provided objective evidence for the efficacy and safety of favipiravir as treatment for COVID-19.

If therapy begins in the first days after the onset of disease, the product significantly increases survival rate, reduces viral load, need for artificial ventilation, and length of hospital stay.

Robert Redfield, a renowned American virologist and former director of the U.S. Center for Disease Control and Prevention (2018–2021), notes: "Avifavir? has been shown to be effective against COVID-19 in clinical trials and medical practice. Recently additional direct acting antiviral have been developed. Studying the combination of Avifavir? with other antivirials such as Paklovid (Pfizer) could offer even better therapeutic options for those at higher risk of COVID-19 disease progression, reduce the likelihood of drug-resistant virus mutations, and increase the time after diagnosis when therapy can be effective."

References to studies supporting the efficacy of favipiravir against COVID-19:

1.  In a multicenter randomized phase II/III clinical trial in patients with moderate COVID-19 (NCT04434248), Avifavir provided effective clearance of SARS-CoV-2 virus in 62.5 % of patients within 4 days, was safe and well tolerated (Ivashchenko А.А. et al. Avifavir for Treatment of Patients With Moderate Coronavirus Disease 2019 (COVID-19): Interim Results of a Phase II/III Multicenter Randomized Clinical Trial. Clin Infect Dis. 2021 Aug 2;73(3):531-534. doi: 10.1093/cid/ciaa1176.). Now we can summarise and supplement both the ChemRar Group data on the use of the product and the findings of extensive scientific research with the product performed around the world.

2.  A systematic meta-analysis of 11 clinical trials has demonstrated that favipiravir causes effective clearance of the SARS-CoV-2 virus by day 7 and promotes clinical improvement within 14 days (Manabe et al. Favipiravir for the treatment of patients with COVID-19: a systematic review and meta-analysis. BMC Infect Dis. 2021; 21(1):489.).

3.  In a randomized, blind, placebo-controlled phase III study of favipiravir efficacy and safety in 156 COVID-19 patients with moderate-to-severe pneumonia (Japan), the median time to patient recovery was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a statistically significant difference (p = 0.0136) (Shinkai M. et al. Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial. Infect Dis Ther. 2021 Aug 27; 1-21.).

4.  Inclusion of favipiravir in the national COVID-19 treatment protocol in Turkey resulted in a pronounced, statistically significant decrease in ICU hospitalization rates from 24 % to 12 % (Guner et al. ICU admission rates in Istanbul following the addition of favipiravir to the national COVID-19 treatment protocol. North Clin Istanb. 2021; 8(2):119.).

5.  In a retrospective study conducted in specialized public hospitals in Saudi Arabia, the median time to discharge for patients with COVID-19 was 10 days in the favipiravir group compared to 15 days in the maintenance therapy group, across all grades of COVID-19 severity (Alamer et al. Effectiveness and safety of favipiravir compared to supportive care in moderately to critically ill COVID-19 patients: a retrospective study with propensity score matching sensitivity analysis/ Curr Med Res Opin. 2021; 37(7):1085.).

6.  In a randomized, open-label, parallel, multicenter phase III study of 150 patients with mild to moderate COVID-19 conducted in India, the median time to cessation of virus excretion was 5 days versus 7 days, and the median time to clinical recovery was 3 days versus 5 days for favipiravir and control, respectively (Udwadia et al. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis. 2021; 103:62.).

7.  Favipiravir has demonstrated efficacy and safety in treatment of mild to moderate COVID-19 in outpatients and hospitalized patients: the median time to clinical improvement was 6.0 days (IQR 4.0; 9.3) in the favipiravir group and 10.0 (IQR 5.0; 21.0) days in the SOC group. The rate of viral elimination on Day 5 in the favipiravir group was significantly higher than in SOC group: 81.2% vs. 67.9% (RR 1.22; 05% CI 1.00-1.48; P=0.022). (Phase 3 trial of coronavir (favipiravir) in patients with mild to moderate COVID-19. Am J Transl Res 2021;13(11):12575-12587)

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Source: The Russian Direct Invest Fund (RDIF)