While scientists have made great strides on the development front for anti-clot vaccines, there is still no “silver bullet” in the form of a highly effective drug against coronavirus. Existing antiviral drugs work either very poorly, or are suitable for a very limited number of patients, or the harm from a side effect outweighs the possible benefit. Recently, however, experts have started talking about a “ray of hope” and even a “radical change” in the fight against infection: its source is called the pills developed by Pfizer. We are talking about a drug with the active ingredient Paklovid (PAXLOVID).
The creators of the drug have published a detailed report on clinical trials in humans. The study was conducted according to all standards of evidence-based medicine: double-blind, randomized, placebo-controlled (that is, all participants were divided into two groups, one was given a drug, the other was given a placebo, a dummy; while neither the medical staff nor the patients knew who got what – from here to the title “double blind”). The pills were taken by 1219 volunteers, including patients with covid from North and South America, Europe, Africa and Asia.
The results look very impressive:
- in patients with COVID-19 who started taking Paklovid 3 days after the onset of the first symptoms of the disease, the risk of hospitalization decreased by 89%. That is, these people did not have serious complications, in which they are taken to the hospital;
- for those who started taking the drug from the 5th day of symptoms, the risk of hospitalization was reduced by 85.2%.
An important point : only high-risk patients were invited to participate in the trials. That is, with concomitant diseases, in which covid most often becomes severe: in patients with diabetes, obesity, cardiovascular diseases, etc.
The drug developers announced that the next step will be to test the effectiveness of the drug in a mild form of infection and even for contact persons who are at risk after communicating with patients.
It is expected that Paklovid may be registered in the United States by the end of this year. Will humanity finally have a life-saving pill that will put an end to the “coronavirus outrage”? We asked Nikolai Kryuchkov , an expert on the development, research and registration of medicines, Ph.D.
PROTOTYPE HAS BEEN HEALED FATAL INFECTION IN CATS
- Nikolay, in the scientific and medical communities in social networks, Pakslovid is actively discussed, they call him a drug “with a cunning warhead.” Is this a completely new class of antiviral pills, or are there medications for other infections that work the same way?
- No, the drug cannot be called completely new, created from scratch. This is a combination medicine. Its first component is “sharpened” directly to counteract the coronavirus. To put it very simply, Paklovid inhibits (neutralizes. – Ed.) A key enzyme of the virus, which is necessary for the “assembly” of new viral particles.
Drugs that work on this principle, the so-called protease inhibitors, are already known and are used in clinical practice. These include, for example, anti-HIV drugs and drugs to treat hepatitis C.
The predecessor of Paklovid appeared and began to be investigated long before the COVID-19 epidemic. The prototype drug (an analogue of the current drug) was tested, in particular, for efficacy against veterinary coronaviruses common in animals. And an inspiring success was achieved: it turned out that the drug works perfectly against a very serious, almost fatal disease in cats, infectious coronavirus peritonitis.
- The second component of the new drug is ritonavir, which is part of HIV drugs. And why is he here?
- The problem is that the first, antiviral component of Paklovid is quickly destroyed by liver enzymes. Because of this, a minimum of the active substance enters the bloodstream, the antiviral effect is insufficient. And ritonavir slows down the work of liver enzymes, inhibiting the destruction of the molecules of the first active substance of the drug.
- Doesn’t it turn out that because of this Pakslovid hits the liver hard?
- Well, you have to understand that this is a serious medicine, not a chocolate bar. Any effective antiviral drug has side effects. But in general, ritonavir has been used for a long time, and it is recognized that the benefits of its use far outweigh the potential risks.
THREE IMPORTANT DETAILS
- Nikolay, when you, as an experienced expert in drug research, get acquainted with the results of the Paklovid trials – how convincing are the successes declared by the developers?
- First of all, it is necessary to clarify that this is not yet a publication in an international scientific journal peer-reviewed by independent scientists (such as was, for example, at Sputnik V in Lancet. – Ed.). Pfizer has posted a press release on the Paxloid Clinical Trials (CI) results on its website . At the same time, we must pay tribute: information with many details and a description of the CI gives reason to believe that, most likely, there is all the necessary data for the scientific recognition of the stated results.
They are really encouraging: in patients with concomitant diseases, the risk of hospitalization (which essentially means the risk of developing severe complications) has decreased by almost 90%. However, there are three important points to keep in mind.
First, a powerful antiviral effect was observed in those patients who started taking the medicine in the first three days of illness. Slightly weaker – when you start taking it on the 5th day after the onset of symptoms. The total course of taking the drug is designed for 5 days, one tablet every 12 hours.
This means that for the effective action of Paklovid, in an amicable way, you need to take a PCR test for coronavirus on the first day of illness.
- Taking into account that the first symptoms of covid in most people do not differ from “ordinary” ARVI, does it become necessary to take not the cheapest test with every sneeze?
- Yes. The second important point: the effectiveness of the drug has been proven precisely in people at high risk of covid complications. We do not know how the drug will work in a mild form of infection, how noticeable its therapeutic effect will be and exceed the risks of adverse events.
Finally, the third very significant nuance. Since Paklovid seriously affects the functioning of the liver, during its use the parameters of “assimilation” of other drugs will change. And we know that people from the risk group have concomitant diseases and need to constantly take at least several drugs: to control blood pressure, blood clotting, blood glucose levels, etc. When deciding on the use of Paklovid, doctors will have to weigh everything very carefully , think over and adjust the regimens for taking other drugs.
Is it a panacea or not?
- Nikolay, from the first days of the pandemic, people have been waiting for the appearance of a medicine that can destroy the coronavirus completely and irrevocably. Will Paxlawid become such a “silver bullet”?
- Based on the published data of the developers, we can talk about the benefits of this drug for certain groups of patients, from risk groups. If everything is finally confirmed, then Paklovid can be considered, although not a panacea, but really a real breakthrough in the fight against coronavirus infection. With the caveats we mentioned above.
- What are the chances that new pills will become available to patients in Russia?
- There are several options for the development of events. On the one hand, the Pfizer company, which has its own representative office, can register and sell Paklovid in Russia. Taking into account the price of about $ 700 per pack for European partners, I think that a package of the drug here can cost about 45 thousand rubles. On the other hand, it is possible that it will be possible to reach an agreement with the developers on the release of generic drugs at Russian production sites (these are analogs of the original drug with the same active ingredient. – Ed.). Then the price will be significantly lower.
If the World Health Organization recognizes Paklovid as an antiviral drug against COVID-19 with proven efficacy, then it is highly likely that the drug will appear in Russian protocols for treating the disease and will be purchased at the expense of the state, the expert believes.