What do we know about the first Russian drug from coronavirus.
Aviewer — trade name of a Russian drug which was developed by the Russian direct investment Fund (RDIF) and a group of companies “Chemrar”. However, the active ingredient of the drug was not invented in Russia.
Its international nonproprietary name — favipiravir (favipiravir). This game was developed by employees of the Japanese company Toyama Chemical, a subsidiary company of Fujifilm Corporation Pharmaceuticals.
According to its chemical structure, favipiravir — derived 6-fluoro-3-oxo-3,4-dihydropyrazine-2-carboxylic acid, or pyrazinecarboxamide. During the screening of chemical libraries employees of the company Toyama found that this ingredient may have activity against influenza virus: once the virus infected the cells, favipiravir turns into the activated form, inhibiting the activity of an important viral enzyme RNA-dependent RNA polymerase.
If “off” RNA polymerase influenza viruses lose the ability to “print” in the infected cells own genetic material, RNA. As a result, the production of virus residing in the cells stops. This is the uniqueness of the drug — usually antiviral medications can only prevent the penetration of viruses in cells.
RNA-dependent RNA polymerase are not only in influenza, but in all RNA viruses. And the catalytic domain RNA polymerase — the so-called area of the molecule, whereby the enzyme can in principle work in all RNA viruses have the same structure.
the Staff of Toyama registered favipiravir under the trade name “Avigan” and began to explore the promising activity of drugs on RNA viruses: from influenza viruses type A and B to the Ebola virus. The results have been mixed. For example, in the case of the Ebola virus revealed that on monkeys, the drug worked, but during the application on humans the result was not very impressive.
on the one hand, the level of mortality in 73 patients from Guinea who received favipiravir was lower than patients who tried to heal in other ways. On the other hand, the difference was not so great: 42.5 percent versus 57.8 percent — that is, there is no guarantee that this is not just a random artifact of calculation due to the fact that the sample of patients was very small. However, the government of Guinea approved the drug as a standard treatment against Ebola virus.
At home drug, in Japan, avian managed to register only in 2014 and only against new strains of influenza virus. Against seasonal influenza avigan was not used.
the drug was approved not just against “new” Gris��PA, but only for situations where existing antivirals have been ineffective — that is, as a last resort. In the six years since the endorsement of such a situation has not arisen even once, so in a real flu epidemic, the drug is never applied.
a Review of 29 clinical trials (4299 participants), six of which were studies 2 and 3 phase (they have assessed the efficacy of a drug), showed that favipiravir “demonstrates favorable safety profile”: the proportion of serious side effects was 0.4 percent. However, problems with the safety of the drug still remain.
Other possible problems: loss of appetite, nausea, vomiting, increased concentration of uric acid in the blood (hyperuricemia) and liver damage.
In March 2020, Zhang Xinmin, Director of the National center of biotechnology, which is part of the Chinese Ministry of health, said that favipiravir “demonstrated good clinical efficacy against the novel coronavirus disease (COVID-19)”.
According to at least one open not a randomized study, 35 Chinese patients with coronavirus disease treated with favipiravir (the study doesn’t say what kind of drug discussed: about the original aviane or Chinese medicine with the same active substance), recovered faster, and suffered less complications than 45 patients who were treated with other medications (lopinavir and ritonavir).
currently, the efficacy of the drug against COVID-19 was evaluated in clinical trials in Japan. 9 APR Fujifilm announced the beginning of the second phase of clinical trials avigan, which will be held in the United States — in the trial will involve 50 patients with coronavirus disease. According to some foreign reports, April-may favipiravir tested in 16 clinical trials, but no one completed clinical trial, which showed that favipiravir or avigan effective against coronavirus disease, no.
Any medication consists of the active substance and filler (finished dosage forms). Russian antiviral drug contains the same active substance, and Japanese drug — 200 milligrams of favipiravir on the pill.
in conversation with N + 1 pointed out by the representative of the RDIF Arseniy Palagin, a filler at the Russian drug your. The manual says that the excipients include microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate and povidone K-30. The term of patent protection on the original Japanese avigan expired in 2019, so the drug can be considered legally manufactured generic.
Ross��iscie clinical trials of avifauna also not finished yet. Completed only 1 and 2 phases of a multicenter randomized study, confirms the source, N + 1 from the FUND. In the first stage of which was attended by 60 people — 20 of them were included in the control group, which was treated by standard methods. Data on age composition and severity of the condition the subjects were not disclosed.
Here that report on the results of these tests by the developers:
the Ministry of health approved the initiation of phase III trials of avifauna may 1, 2020, in him, according to the State register of medicines will be required in total to take part 390. The same data shows that the test favipiravir spend another two Russian companies — “Technology of drugs” (enters into group “R-Pharm”), and “Promomed”. Both companies began testing in late may.
Although the test is not completed, and only partial data is known about the effectiveness, the Ministry of health was allowed to register the drug early under the accelerated procedure adopted in the framework of the decree of the RF government of 3 April 2020, No. 441. This resolution States that “the reduction … of expertise” permissible “under the threat of occurrence and liquidation of emergency situations”.
So manufacturer will by the end of next week to bring the first batch of pills in a hospital.
In the instruction says that it is “prepared on the basis of a limited amount of clinical data on the drug and will be supplemented as new information becomes available”. However, already defined contraindications. As in the case of Japanese Avignon is pregnancy planning, pregnancy and breastfeeding — generic is also potentially teratogenic. Patients with gout and hyperuricaemia to apply the medication should be cautious. In addition, the list of contraindications to the Russian generic complements hypersensitivity to the active substance, the age of 18 years, severe liver and renal failure.
Aviewer — generic medicinal product of favipiravir, which has a distinct mechanism of action, and which is undergoing clinical trials in Russia and abroad.
interim Results of clinical trials show that the drug is promising: on those small samples, that it was time to test the therapeutic effect, according to the developers, to determine managed. But until clinical trials are not complete, and their results are not published in peer-reviewed international journals, we cannot be completely sure that aviewer really helps with the coronavirus disease. PreSS-service “Chimera”, the inventor of the drug at the time of publication of this text, the questions N+1 has not responded.
Now we have no medicine which is deliberately and effectively acted against the virus SARS-CoV-2. All the contenders for the title now — substances known to the emergence of a new coronavirus, which is in clinical trials (literally just started) consistently show some positive effect with a number of limitations. Their now — two.
the First is ramdevpir, did not descend from the front pages in may is a cure that even prior to the epidemic, COVID-19 intended for the treatment of other coronavirus infections middle East respiratory syndrome (MERS). The U.S. regulator has approved the clinical use of ramdevpir, without waiting for the formal end of the test drugs to having a stable effect in preliminary of these studies convinced the medical officials. This situation compared with the early registration of AZT, the first HIV drugs.
Many other effects — for example, the mortality of the disease compared to other drugs, with statistical significance in these tests show failed. Sample testing of ramdevpir, the report of which was published in the end of may the New England journal of Medicine, amounted to 1059 people.
Favipiravir as ramdevpir, was not originally designed as a means against the new coronavirus. The drug many years ago — so much so that the patent on it had expired — was adapted for the treatment of influenza (strictly new virus, but not seasonal diseases), and tested against the viruses of Ebola and Zeke.
Yes, the Russian researchers seem to have managed to catch the effect of its use in the treatment of COVID-19 — but on a small sample of 60 detailed information about the methods of selection and which not.
So the pills we seem to have. And to ensure that it really is the cure, will have to wait a little longer.
Daniel Davydov
