Destroy the virus in five days

Peter Bely, Chairman of the Board of Directors of Promomed Group of Companies, about a new drug for the treatment of coronavirus infection.

A new drug for the treatment of coronavirus infection, esperavir, was registered on February 3 by the Ministry of Health of the Russian Federation. A week later, Promomed, the company that developed the drug, began supplying it to the healthcare system. Peter Bely, Chairman of the Board of Directors of Promomed Group, spoke in an interview with Kommersant-Nauka about the hopes that esperavir gives in the fight against COVID-19.

— Why do you need esperavir if your company already has a proven anti—covid drug in its portfolio - areplivir?

— Esperavir is a new word in the treatment of coronavirus. He is able to provide an almost complete recovery in just five days. Both international and Russian clinical studies on molnupiravir show that within five days of therapy, even patients with risk factors (diabetics, obese people, people over 60 years of age) achieve complete recovery, that is, level zero on the World Health Organization scale characterizing the patient's clinical status ("recovery, absence of clinical symptoms"). We are very pleased to emphasize that we were among the first to complete these studies and contribute to the world's collection of data on its effectiveness and safety. The premiere of the drug, thanks to the efforts of developers, scientists, and our team, took place almost simultaneously with the world's leading economies.

— What is the mechanism of action of esperavir?

— Esperavir is based on molnupiravir, a derivative of a well-known substance with proven antiviral activity of N4-hydroxycytidine. Esperavir has two mechanisms of action: firstly, due to its effect on the unique native targets in the RNA-dependent RNA polymerase of the virus, it blocks its reproduction and, secondly, triggers the mechanism of lethal mutagenesis.

— How did your company start working on esperavir?

— As you know, medical developments last for years and even decades. When the world was faced with the new coronavirus, experts began to think about which molecules could be suitable for creating a drug, which processes of coronavirus activity in the body could be influenced. Someone decided to rely on the S-protein, someone on the fusion of the virus with the cell, someone on the replication of the virus, as our company did. So at one time we came to the need to bring areplivir (favipiravir molecule) to the market. Our work in this area has led us to understand that a doctor should have more effective and fast-acting drugs in his arsenal. Therefore, while still working on areplivir, we decided to focus on N4-hydroxycytidine derivatives, which act on other enzyme sites other than favipiravir, thanks to which the virus replicates (multiplies). This gives the doctor more range to make decisions about choosing the most effective therapeutic strategy.

— If esperavir is more effective than areplivir, maybe then areplivir is no longer needed?

— First of all, both drugs are needed. Esperavir (molnupiravir), as we can see from international and proprietary data, is very effective in the early days of the disease, so that the course of treatment can be reduced to five days. On the other hand, areplivir is proven to work at all stages of the disease, including moderate and severe, and is used even in hospital therapy. Treatment can be started at any stage of the disease.

Esperavir is very effective when it is taken in the first days of the disease, or better yet, in the first hours. At the same time, esperavir can be used not only after laboratory confirmation of the fact of coronavirus infection, but immediately after the appearance of the first symptoms of coronavirus based on the clinical picture and for five days. The issue of its effectiveness in delayed use has yet to be studied in the general population. There are no such questions about areplivir anymore.

— Why treat a mild course of the disease?

— This is the most important issue. It is absolutely necessary to treat. Yes, COVID-19, especially the omicron strain, can occur very easily. But it can trigger a cascade of pathological reactions, long-term and severe in terms of subsequent treatment.

The topic of the so-called long covid (post-covid syndrome) is becoming increasingly important. Scientists associate the development of this condition with the long-term persistence (vital activity) of the virus in the body, even in a latent form. Very often, long-term covid is noted precisely in those who have suffered the coronavirus disease easily, that is, in people who have not been treated correctly and have not achieved the elimination of the virus. The director of the Scientific Center of Neurology, Academician Mikhail Piradov, told me that 88% of patients who have had coronavirus infection havefecal discharge with symptoms, neurological complications occur. First of all, asthenia, weakness, which can last for weeks. This also includes depression, fortunately reversible, of cognitive functions, mnestic functions: decreased memory, mental performance.

Complications from the cardiovascular system are well known, including the risks of thromboembolism leading to cardiovascular disasters. This condition can last for months.

How to avoid all this? Start treatment as early as possible and prevent a cascade of pathological reactions from starting. In this sense, there is no difference between a light current and a moderate current and a heavy current. The patient needs to be treated, and viral replication and the increase in viral load must be stopped as early as possible.

Therefore, the guidelines for long-covid already indicate the need for antiviral therapy. Even in patients with mild disease, it is necessary to achieve complete elimination of the virus.

— What is the current state of esperavir production? Will your company's facilities be able to handle the health care demand?

— Production is fully operational. The procedure for registration of medicines involves, among other things, the procedure of post-registration state control. Immediately after its completion, healthcare institutions began receiving the drug, and the first batch was shipped to medical institutions and pharmacies on the night of last Wednesday to Thursday. We do not know how the morbidity situation will develop, perhaps we still have no idea what scale we will have to face, but we will do everything to provide all medical facilities. The production works around the clock.

— Will Esperavir be a prescription drug?

— Absolutely. The decision on his appointment and treatment strategy will be made by the doctor. What decision should the patient make? Start receiving antiviral therapy as early as possible! There is a common mistake that patients make. There is a pandemic outside the window. A person feels the first symptoms of the disease, but decides: "I guess that's not what I have. Maybe he just caught a cold." These words, "I must have something wrong," are very scary. The first thing to do at the first sign of illness is to seek medical help. To the local doctor, through telemedicine, to the Stopcoronavirus operation center hotline — through any channel. After such treatment, a person will usually receive a free package of a highly effective antiviral drug from a doctor within a very short period of time. Then he will have a very high chance of a quick cure of the disease, and most importantly, to eliminate the risks of serious complications.

— Is the share of imported ingredients in esperavir high?

— The drug is completely domestic. It is produced at our Biochemist plant in Saransk.

— Has your company patented esperavir?

— This is a very interesting situation that has arisen at the intersection of science, regulation, and global patent practices. So far, there is not a single valid patent in Russia. Many applications have been submitted related to the molnupiravir molecule, its active metabolite, compositions, methods of application, etc. Among the large number of applications, foreign and domestic, there is also an application from Promomed. Scientists, clinicians, and representatives of the pharmaceutical industry are watching with great interest how this situation will be resolved. Which patents will be granted, which patent applications will be rejected, and what the regulation of this area will look like in the end.

Our patent regulator will deal with the patent situation. But here's what I wanted to pay attention to, that's what's important. Our country has a high level of patent regulation and a high rating from the point of view of the World Intellectual Property Organization (WIPO), the Eurasian Patent Organization (EAPO). But people are suffering from coronavirus infection now. People should receive effective, state-of-the-art therapy today.

Esperavir appeared in Russia almost simultaneously with the introduction of molnupiravir drugs in the USA, Great Britain, other European countries, and Japan. One of the most modern achievements of the global pharmaceutical industry is now in service with our doctors and our healthcare system.

— What can a patient who has received esperavir expect while he is taking the drug?

— The patient doesn't have to wait for anything. The patient must be confident. This is indicated by the very name "esperavir". In several European languages, "espero" means "hope." I repeat, clinical studies show that fever disappears on the first or second day, and then the symptoms of coronavirus infection continue to weaken. The drug is very easily tolerated and has a clinically proven beneficial safety profile.

Given the growth rate of the number of cases and the number of hospitalized, the health systemThere is a huge burden on security. Esperavir has been shown to reduce the risk of hospitalization. It is very important that there is a drug that can be used on an outpatient basis and give quick results. In five days, the virus is eliminated from the body, and the sick person does not go to the hospital. And those comorbid severe patients who will still be hospitalized will receive the best therapy, timely and in full, since with proper outpatient therapy, the burden on hospitals will be reduced.

— Hopefully, the pandemic will end sooner or later. In this case, who will need huge stocks of antiviral drugs?

— You don't need to make forecasts, you need to analyze trends. At the moment, they are as follows: we are seeing a strong surge in morbidity and the number of hospitalizations. Antiviral drugs are needed here and now. We must give the healthcare system the means of therapy.

In addition, I would like to remind you that esperavir is a drug with universal action directed against the replication of RNA-containing viruses. It is impossible to assume that the coronavirus will disappear altogether. Even if it mixes with common acute respiratory viral infections, people with risk factors will also be at risk of complications, so they need effective therapy. Naturally, Promomed will study its effects on other viruses: influenza, noravirus and other SARS pathogens. In addition, the possibility of post-exposure prophylaxis of the disease using this drug is being discussed. When relatives live with a patient with COVID-19 or there are sick people in the workforce, the risk of infection is high. It is better to prevent the disease than to deal with complications later.

Post-exposure prophylaxis should become a separate area of research. After all, it is much better not to fight the outbreak of the disease, but to make sure that this outbreak does not occur.

Recently, there was an article in the journal Nature stating that there are hundreds of viruses that can pass from animals to humans, as happened with the new coronavirus. It is very important that the pharmaceutical industry can react quickly and understand which mechanism of action of the virus in the body can be affected in order to defeat it quickly. We are learning this now.

By bringing products such as esperavir to the market, we are building a foundation for the future. In the event of a new pandemic, we will be prepared for it. Esperavir is not only a new word in therapy, it is also a new hope that even more human lives will be saved.

Source: www.kommersant.ru

Sources

1. https://www.kommersant.ru/doc/5215339