Destroy the virus in five days

Promomed 11 February 2022

Chairman of the Board of Directors of Promomed Group Petr Bely speaks about a new drug for the treatment of coronavirus infection

A new drug for coronavirus infection, Esperavir, was approved on February 3 by the Ministry of Health of the Russian Federation. A week later, the drug developer Promomed Group started supplies to the healthcare system. Kommersant-Nauka interviewed Petr Bely, Chairman of the Board of Directors of Promomed Group, about hopes Esperavir gives us in the combat against COVID-19.

— Why do you need Esperavir if your company's portfolio already has an anti-covid drug Areplivir with proven efficacy?

— Esperavir is an advance in the treatment of coronavirus. It is able to provide an almost complete recovery in just five days. Both international and Russian clinical studies on molnupiravir show that even patients with risk factors (diabetics, obesity, age over 60 years) achieve complete recovery within five days of treatment, that is, zero level on the WHO scale of patient’s clinical status (“recovery, absence of clinical symptoms”). We are very pleased to emphasize that we were one of the first to complete these studies and contributed to the world's data set on its efficacy and safety. Thanks to the efforts of developers, scientists, and our team, the drug was launched in Russia 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 known substance N4-hydroxycytidine with proven antiviral activity. Esperavir has two mechanisms of action: firstly, due to the impact on its own unique targets in the RNA-dependent RNA polymerase of the virus, it blocks its reproduction and, secondly, it 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 a novel coronavirus, experts began to think about which molecules could be used to develop a drug, what processes of coronavirus activity in the body could be targeted. Someone decided to bet 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) to the market. Work in this area has led us to the understanding that doctors should have a choice of more effective and fast-acting drugs. Therefore, while still working on Areplivir, we decided to work on N4-hydroxycytidine derivatives, which act on other sites of enzyme, thanks to which the virus replicates, as compared to favipiravir. This provides a greater choice for the doctor in making decisions about the most effective therapeutic strategy.

— If Esperavir is more effective than Areplivir, maybe the latter is no longer needed?

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

Regarding Esperavir, it is very effective when taken in the first days of the disease, and preferably 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 first symptoms of coronavirus appear, on the basis of the clinical pattern and for five days. The issue of its efficacy in case of delayed use has yet to be studied in the wider population. There are no such issues with Areplivir.

— Why treat a mild course of the disease?

— This is the most important question. Treatment is definitely needed. Yes, COVID-19, especially the Omicron strain, can be very mild. But it can set off a cascade of pathological reactions that are long-term and difficult in terms of subsequent treatment.

Now the so-called long COVID (post-covid syndrome) is becoming increasingly important. Scientists relate the development of this condition to the long-term persistence (life activity) of the virus in the body, even in a latent form. Very often, long COVID is observed exactly in those people who had a mild coronavirus disease, that is, who were not treated correctly and failed to achieve elimination of the virus. Director of the Scientific Center for Neurology, Academician Mikhail Piradov, told me that 88% of patients who recover from coronavirus infection with symptoms develop neurological complications. First of all – asthenia, weakness, which can last for weeks. This also includes oppression, fortunately reversible, of cognitive functions, mnestic functions: memory loss, mental performance.

Cardiovascular сomplications, including the risks of thromboembolism, leading to cardiovascular catastrophes, are well known. This state can last for months.

How to avoid all this? Start treatment as early as possible and prevent the cascade of pathological reactions. In this sense, there is no difference between mild, moderate and severe course of disease. The patient must be treated and viral replication and viral load growth must be stopped as early as possible.

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

— What can you say about production of Esperavir? Will your company's capacities cope with the healthcare demand?

— Production facilities are 100% ready. The procedure for approval of medicinal products involves, among other things, postmarketing inspection by state authority. Immediately after its completion, healthcare institutions began to receive the drug; the first batch was shipped to medical institutions and pharmacies already on Wednesday night. We do not know how the pandemic situation will develop in terms of the incidence, perhaps we still have no idea what proportions of events we will have to face, but we will do our best to maintain supplies to all medical institutions. The production facility operates continuously around the clock.

— Will Esperavir be a prescription drug?

— Certainly. The decision on its use and on the treatment strategy will be made by the doctor. What decision should the patient make? Begin antiviral therapy as soon as possible! There is a common mistake that patients make. It is pandemic time. A person feels the first symptoms of the disease, but decides: “Probably, it’s not my case. Maybe I just caught cold." These words “probably, it’s not my case” are very dangerous. The first thing to do at the first sign of illness is to seek medical help. To the primary care physician, through telemedicine, to the hotline of the Stop Coronavirus headquarters – through any channel. As a rule, within a very short time after that the doctor will provide the patient with a free package of a highly effective antiviral drug. Then the patient will have very high chances of a quick recovery, and most importantly, to prevent the risk of severe complications.

— What is the share of imported components in Esperavir?

— The drug is made of domestic components only. It is produced at our Biokhimik plant in Saransk.

— Has your company patented Esperavir?

— This is a very interesting situation that has arisen at the intersection of science, regulation, global patent practices. So far, there is not a single valid patent in Russia. Many applications have been filed 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. What patents will be issued, what patent applications will be rejected, what will the regulation look like in the end in this area.

Our patent regulator will clarify the patent situation. But here's what I wanted to draw attention to, something that is 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 sick with coronavirus infection right now. People need to get effective, state-of-the-art therapy today.

Esperavir appeared in Russia almost simultaneously with the appearance of molnupiravir products in the USA, Great Britain, other European countries, and Japan. One of the most modern achievements of world pharmaceuticals is now available for our doctors, our healthcare system.

— What can a patient who received Esperavir expect while he or she is taking the drug?

The patient should not expect this or that. The patient must be sure. This is evidenced by the very name "Esperavir". In several European languages, "espero" means "hope". Let me repeat – clinical studies show that already on the first or second day, the fever disappears, and then the symptoms of coronavirus infection continue to weaken. The drug is very well tolerated and has a clinically proven favorable safety profile.

Given the rate of increase in the number of new cases and hospitalizations, the health care system is under a huge burden. 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 a quick result. The virus is eliminated from the body in five days, and there is no need to admit patient to hospital. Rgearding comorbid severely ill patients who will still be hospitalized, they will receive the best therapy, timely and in full, since with the adequate outpatient therapy, the burden on hospitals will be reduced.

— Hopefully the pandemic will end sooner or later. Who will need huge stocks of antiviral drugs in this case?

— No need to make forecasts, you need to analyze trends. At the moment they are as follows: we are seeing a huge surge in the incidence and number of hospitalizations. Antivirals are needed here and now. We must provide the health care system with the means of therapy.

In addition, let me remind you that Esperavir is a drug with a universal action against the replication of RNA-containing viruses. It is impossible to expect that one day the coronavirus will totally disappear. Even if it mixes with common ARVI, people with risk factors will also be at risk of complications, so they need effective therapy. Naturally, Promomed Group will study the effect of Esperavir on other viruses: influenza, noravirus and other ARVI pathogens. In addition, the possibility of post-exposure preventive treatment using this drug is discussed. When relatives live with a patient with COVID-19 or someone works side by side with a sick workfellow, 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 line of research. After all, it is much better to prevent the disease outbreak than to be forced to combat it.

Recently, there was an article in Nature stating that there are hundreds of viruses that can pass from animals to humans, as happened with the novel coronavirus. It is very important that the pharmaceutical industry be able to respond quickly, to understand which mechanism of viral action to target in order to quickly defeat it. Now we are learning this.

By bringing products like Esperavir to market, we are setting the stage for the future. In the event of a new pandemic, we will be prepared for it. Esperavir is not only an advance in therapy, it is also a new hope that more human lives will be saved.