Apart from the obvious problems with the absence of vital drugs in the country, the Ministry of Healthcare also has some time bombs in its arsenal. The name of one of them is Cagocel.
What is happening in Russia’s public health service is partially similar to genocide of the country's population. Recently, wek.ru has written about mucoviscidosis patients, whom state agencies have deprived of vital drugs. There are still no medicines for them, and after our article was published, several people have already died without proper treatment. Next in line are individuals with insulin-dependent diabetes, cancer patients, HIV-positive people, etc. It should be mentioned that these are mass diseases, and the issue concerns millions of hostages of the state policy of drug imports substitution.
Meanwhile, the Healthcare Ministry has managed to cause a shortage of medicines without rhyme or reason. For instance, old drugs which had proved themselves over 50 to 30 years were absent for months from pharmacies because someone in the ministry had started their re-registration. However, the drugs that do not seem to have passed the full cycle of research, ironically, have a free access to the market.
The Country of the Victorious Shamycin
At first glimpse, Cagoсel is one of a great number of the so-called "shamycins" -- sham medications with no benefit and no particular harm. Grippferon, Arbidol, Amoxin, Anaferon, Ingavirin, Viferon, Polyoxidonium.... How many have been seen on pharmacy shelves! They are like fashion: they replace one another. They do not treat but, seemingly, do damage only to the bank accounts of credulous patients who unconditionally believe the persuasive advertising and doctors from district outpatient clinics. As a rule, all these "shamycins" were developed by scientists inside Russia and have no analogues in other countries but exhibit antiviral and immunomodulatory properties. Therefore, they "treat" respiratory viral infections and are prescribed for "immunity improvement" during the epidemic season of ARVI.
Are these "sham medications" as harmless as one might think? Unlike real worthless drugs causing the placebo effect, they contain active ingredients. So, Cagocel contains gossypol, a highly toxic natural substance derived from cotton. As it is known, the difference between a poison and a drug is in the size of the doze, and a lot of drugs are made of poisonous plants.
Therefore, studies in animals have shown that while gossypol diminishes resistance of the human body to infections and the effectiveness of vaccines, it still has an amount of potential properties that can be used to treat severe pathologies, including oncology. But “the immunotoxicity of gossypol has not been fully studied; extensive research is needed to develop more effective and reasonably priced technologies to reduce toxicity of gossypol,” a group of foreign scientists said. In 2014, they published the results of their research in The Scientific World Journal (the article was posted on the website of the National Library of Medicine of the National Institute of Health.)
Therefore, the evidence-based medicine still does not know any drugs developed on the basis of poorly studied and toxic gossypol. There are only two countries, Russia and Uzbekistan that produce and sell drugs which are derivatives of gossypol. Moreover, they are used for treatment of chlamydia and herpes in Uzbekistan, and only in Russia, Cagocel, the derivative of gossypol, is prescribed to everyone, even to children from three years old as a prevention of ARVI.
The fact that the widely advertised Cagocel which was sold over the counter and prescribed to children might be toxic, was first mentioned in Russia about eight years ago. The information that the "harmless" Cagocel contains gossypol, which may cause male infertility, appeared mostly in blogs. The substance was said to be so efficacious that in China it was scrutinized as a potential contraceptive and an alternative to vasectomy. However, as the study progressed, it became clear that when used for a long time, gossypol leads to irreversible changes in spermatogenesis, and it also affects the reproductive function of women and the development of pathologies in embryos. These publications had no impact on the production and sale of Cagocel. Its victorious march was only gaining momentum.
Stages of a Long Journey...
Cagocel was developed by Felix Yershov, an academician of the Russian Academy of Medical Sciences and director of the N.F. Gamaleya Research Institute of Epidemiology and Microbiology, and Vladimir Nesterenko, the head of the immunology department at the same institute. In 1989, they set up the company Niarmedik on the basis of the Institute.
In 2003, Cagocel was registered and its production came on stream.
Since 2005, Cagocel has been produced as an over-the-counter medicine.
The Ministry of Health includes Cagocel on a regular basis in clinical guidelines for influenza and ARVI.
Since 2010, Cagocel has been included in the List of Vital and Essential Drugs which gives it direct access to the public procurement market. The drug must be purchased by hospitals, psychoneurological boarding schools and health centers.
Since 2011, the health authorities permitted prescription of the drug for children as of the age of three years old to treat influenza and ARVI.
In 2011, Niarmedik Group and the government-run corporation for nanotechnologies development Rusnano signed an agreement on cooperation in the Niarmedik Pharma project for building a plant to produce the drug in the Kaluga region. Rusnano has invested 1.2 bln rubles in the project, the total area of the compound amounted to 22,000 square meters. In 2013, Rusnano left the project.
Niarmedik Pharma was built in Obninsk, Kaluga region, with Rusnano money. In September 2019, it produced 200 millionth package of Cagocel.
From one year to the next, the medicine gets top awards: the Product of the Year in the category of Antimicrobial drugs for systemic use, Russian Pharma Awards in the category The Most Prescribed Drug for Treatment of ARVI and Influenza, and the Green Cross in the category The Best for Prevention and Treatment of ARVI and Influenza According to Pharmacy Chains.
In 2017-2019, law enforcement agencies became the largest purchasers of Cagocel. The Ministry of Internal Affairs, the National Guard of Russia, the Ministry of Defense and the Federal Security Service purchased 117,000 packages of the antiviral drug. The National Guard of Russia bought the most -- almost 56,000 packages. Given that the active substance of the drug is proven to cause infertility, the impact of those purchases will certainly affect the population of the country over time.
What Is Your Evidence?
In December 2019, Federal Service for Surveillance in Healthcare (Roszdravnadzor) officially announced that the antiviral drug Cagocel is absolutely safe. This statement was made in response to a request from Lilia Shakirova, Sputnik FM radio host. Many media reprinted the news without verification. Meanwhile, you can listen to what Shakirova said on air on the website of radio Sputnik FM. She read out a written reply of Roszdravnadzor which follows that (quotation):
"Preclinical studies of reproductive toxicity conducted by the developing company of Cagoсel did not reveal the impact of the drug on the animals’ reproductive system.” According to the developers of the drug as well as the Health Ministry and Roszdravnadzor that are actively promoting it, the testing on laboratory rodents is enough to prescribe the medicine to everyone, including 3-year-old children, to sell it over-the-counter in all pharmacies in the country, as well as to buy it for the army and other law enforcement agencies in large dozes.
In 2015, the Dozhd TV channel (TV Rain) hosted a live debate between Anatoly Chubais, the Rusnano board chair, and Alexei Navalny, founder of the anti-corruption fund. The inefficient spending of funds was Navalny’s main claim. Most questions concerned support of the dubious drug Cagoсel, which Chubais called the "pearl" of Rusnano's achievements. In response, Chubais published a list of preclinical and clinical trials of the medicine in his blog, but it caused even more questions. For example, how do drugs get to the market without clinical trials, and even more, to the List of Vital and Essential Drugs?
The global research standard for a new medicine has several mandatory stages: preclinical, clinical and post-registration studies. Each next stage is possible only after the previous one has been successfully completed.
Preclinical trials include laboratory examination of biological, microbiological, pharmacological, chemical, physical and toxicological properties of a new drug on isolated human tissues in a test-tube -- in vitro -- and on laboratory animals - in vivo. However, at the stage of preclinical studies it is impossible to understand how the medicine will function in the human body, as the body of a laboratory animal is very different from the human one, so after the successfully conducted preclinical studies clinical trials are necessarily conducted on human volunteers. They consist of several phases. In any of them, the clinical trial can be terminated, and the drug can be prohibited if it is dangerous to the health of the test persons. The main principle of clinical trials is voluntary participation in them.
There is a visual table of clinical trial phases below:
Phase III is the most important. Only a drug that has successfully passed this stage gets the right for registration and can be released to the market. It is carried out by a double blind random placebo-controlled method, which means that the participants are divided into two groups in randomized ways: one group is given a real medicine and the other – an innocuous medication. Neither the test persons nor the experimenters know who is receiving a drug and who is taking a placebo. Sometimes in order to show that the new drug is superior to its existing counterparts (otherwise, why is it needed?), the controlling group is given another drug with proven effectiveness instead of a placebo.
Before the registration and entry into the market, Cagocel (as well as other domestic "unique" drugs) had only preclinical trials. That is, in a test tube and testing on animals. There were no trials on human beings. In 2015, this was found out by physician-therapist and cardiologist Yaroslav Ashikhmin, a candidate of medical science and a member of the American Heart Association and the European Society of Cardiologists. He studied the list of trials and publications on the drug provided by Anatoly Chubais. Ashikhmin wrote an article about his investigation.
From the article by Yaroslav Ashikhmin:
"All English-language articles (including those in Anatoly Chubais' post) are not clinical studies but Cagocel's reviews and trials of immune response modifiers carried out on cell cultures and laboratory animals. They only cover the very early stage of the drug creation process. The whole history of pharmacology shows that a simple transfer of their results to people might lead to numerous complications.
Most of the publications mentioned by Chubais are just literature reviews, studies of poor quality without any randomization, or sometimes even outright agitation. There are several randomized clinical trials but none of the entire pile of materials meets rigorous evidential criteria.
The "most convincing" trials of the records were carried out as "masked clinical ones". In other words, the researchers knew who got Cagoсel and who got placebo. This knowledge might have affected the results. Only 81 people were included in the first research and 60 children, in the second one.
The trials say nothing about what methods of statistics were applied. There were no initial characteristics of the studied patient groups, on the basis of which the conclusion about their comparability was made. The errors are so grave that no respected medical magazine, either Western or Russian, has accepted these studies. That is why all of them were published in the "second league" media, which may have neither a scientific editor nor reviewers at all.
[...] no phase III studies have been conducted on adults (without which registration is practically impossible) and no phase II studies on children (necessary for safety assessment and dose calculation). It is impossible to find the results of the mentioned key phase II influenza treatment and prevention studies that included 262 and 719 adult patients with influenza and ARVI respectively. Most likely, they have not been published at all.
By the way, all the main reviews of Cagocel's studies refer to the unpublished (!) article written "on the platform of the Influenza Research Institute of the Russian Academy of Medical Sciences, the Virology Research Institute and the Institute of Virology of the Russian Academy of Medical Sciences n.a. D.I. Ivanovsky and the Kirov Military Medical Academy in St Petersburg in the period of 2000 through 2003,” which included Cagocel and placebo groups of exactly 550 patients each.
Alas, today, the situations similar to the one around Сagocel, where a drug which has not passed the mandatory tests, is not only released to the market, but also gets into the List of Vital and Essential Drugs, are becoming typical for Russia. There is an absolute chaos in the local pharmaceutical business. Other well-known "antiviral" drugs are no better than Cagocel. Some of them have been studied even worse than that and quite possibly they are even more dangerous.
In December 2019, Ashikhmin told the Daily Storm publication that nothing has changed in recent years. "And why would they change anything if business already brings in billions?" His words fully match the Roszdravnadzor official response quoted above.
The Black Box of Healthcare Ministry
Only 16 years have passed since Cagocel appeared on the market, and the Russian Academy of Sciences finally doubted the effectiveness and safety of domestic medicines. Academicians tried to find on the official website of the Healthcare Ministry the results of examination of the efficiency and safety of these medicines. And they failed. Then Alexei Khokhlov, the curator of the Russian Academy of Sciences’ committee to counteract false scientific research and vice-president of the academy addressed the ministry with a question: where are the conclusions? The ministry replied that it publishes them in the private part of the website so only the producer has access because if the conclusions of the examination are published with an open access, it can violate commercial confidentiality.
This answer puzzled the academicians. “Experts know that if there is no information about the research, it means that either there was no research itself, or the results were negative,” Peter Talantov, the press secretary of the Academy of Sciences’ committee told reporters.
"Drug registration should not be a "black box": the government, the professional community and consumers should clearly understand on the basis of what scientific data about the effectiveness and safety of a particular drug is used,” says Talantov. “Transparency makes it possible to double-check the information, identify violations and sound the alarm on time. If the information is not open to the public, the drug registration process becomes a black box for public safety and budget rationality.”
The editorial staff of wek.ru sent official letters to the Healthcare Ministry and Niarmedik Plus with the question "Where can we see the results of clinical trials on the effectiveness and safety of Cagocel?” Despite numerous promises made by officials, there is no response after four weeks since then. Following examination of the information available, we understand why we have not received an answer: it seems such studies have never been conducted.
It turns out that neither the Ministry of Health, nor Roszdravnadzor, nor the producer itself can guarantee that the drugs sold in pharmacies and prescribed in hospitals treat but do not harm people.
The absence of reliable information about Cagocel is going along with massive and aggressive advertising of it. In the next article we will tell you how Niarmedik drives false information about its product into consumers' heads.