Medical research and development are in the center of everyone’s attention nowadays, and that includes politicians. This inevitably means that science becomes a subject of dangerous compromises.
These days biomedical innovation grabs everyone’s attention, it is the focus of politicians as well, which leads to disturbing compromises.
As the disease of COVID-19 transmitted from people to the national economies, drug development started to get politicized. For months, the pharmaceutical industry was holding the line as they are used to do and gave monotonous explanations of what is possible at the current level of medical technologies. However, in recent weeks they have surrendered to the pressure of the public and joined the auction of unrealistic promises.
US President Donald Trump made an announcement that the mass manufacturing of the vaccine would begin before the end of the year, or even by the fall. Many public pharmaceutical companies, as well as some small biotechnological developers, joined the race of promises. At the very same time, the chief infectious diseases expert in the USA Anthony Fauci has already promised a vaccine in 12-18 months, in other words, sometimes within the first three quarters of the next year.
But even 12-18 months will not be enough for a full cycle of research. The only thing that we may get in a year and a half might be an insufficiently tested vaccine that will likely be approved out of sheer lack of options and then used primarily in high-risk groups. In a number of countries, the first to get it will be doctors, seniors, and people suffering from chronic diseases. Then, when mass production gets set up (which is going to take many more months), deliveries into other countries, those capable of paying for it, will start. It will not be even close to everyone who will be able to get the vaccine within a year of its approval.
It is possible that this is all for the best. You shouldn’t rush to be first in line to get vaccinated. All of the new products that are being approved right now, the drugs and the tests alike, are of inferior quality, which is inevitable. The vaccine will have risks associated with it that will not be evaluated or checked.
Possible long-term effects are much better studied on a test group in a controlled clinical trial environment, not on millions of healthy people. The risks should not outweigh potential benefits, considering that for the vast majority of people COVID-19 is asymptomatic.
And in any case, one should not be in any rush to get sick for the sake of “herd immunity”, either. The later you get sick (if you get sick at all), the better treatment you will be getting. The clinical practice guidelines are getting updated every single day, we are constantly learning a lot of new things about the SARS-CoV-2 virus, as well as of the COVID-19 disease itself. It has already been established that it is necessary to monitor not just the lungs and that this new coronavirus infection is not only causing pneumonia but also creates blood coagulation problems and organ failure. Each type of pathology has its own dedicated drugs that are already being utilized. The first step in reducing COVID-19 mortality will be using sets of these existing drugs for treating particular issues. If you are to get sick in October instead of June, it would not only “flatten the curve” of the healthcare industry’s workload, but also increase your personal chances of being treated with those drugs whose effectiveness has been proven and whose side effects are less severe.
Why were we caught defenseless?
One of the major questions we are concerned with is why the world was not ready for the pandemic. After all, everybody knew that one was inevitable. Doctors and health care officials encounter dangerous viruses on a regular basis: the avian flu, the swine flu, Ebola, and the previous SARS and MERS coronaviruses. There have been many popular Hollywood disaster movies filmed about the risks of a pandemic, Bill Gates has used all available communication channels to talk about them.
The emergence of a new pandemic-causing virus or of a superbug immune to any existing antibiotics was only a matter of time.
Unfortunately, there is a problem with the lack of sufficient funding at all of the stages of development in the field of anti-infection medicine research. It is impossible to quickly develop a drug against a new SARS-CoV-2 virus unless there have been many years spent by the researchers, receiving a stable salary, on methodically studying hundreds of strains of coronaviruses. However, the research studies of the previous SARS and MERS coronaviruses were funded only during the time the epidemic was going on, accompanied by a barrage of publications in the mass media and the scientific journals. And, as soon as the infection would wane, without having affected the developed countries, the inflow of funding would dry up with it. The development of a high-quality vaccine would require more than 10 years, and the recent epidemics have not lasted very long, usually coming and going in relatively short waves.
Thus, what we have is a vicious circle: when there is an epidemic, there is no vaccine; when the epidemic is over,the vaccine is no longer needed, and along with it the fundamental studies of the pathogens are not needed anymore either.
In the case with SARS-CoV-2, we do have a chance to break out of the cycle and succeed in the development and testing of not just a vaccine but a fundamentally new technological platform for combating viruses, which would prove to be useful to the mankind even after the current pandemic curve subsides. We are talking about creating technological platforms for the manufacturing of vaccines based on the genetic code of the virus, which would include RNA vaccines. There are several companies working on the RNA vaccine now, including the Russian BIOCAD and the American Moderna, which is already conducting clinical trials of its RNA platform on humans.
Technological platforms of this kind can potentially be a game-changer in the fight against viral infections. There is a chance that future development of such vaccines would take less time than that of the traditional vaccines, and that they would turn out to be safer, more effective, and easier to manufacture.
It is not the viral proteins themselves that would be introduced into the body, but rather their RNA code. Human cells themselves would become a factory for manufacturing the antigen. And, should there appear yet a different virus with a different RNA tomorrow, theoretically, it should only be enough for the developer to change the RNA code of the vaccine and start manufacturing it at the very same facility, which is much easier than conducting research and setting up production of a new protein-antigen.
Thus far no one knows if this technology will work against SARS-CoV-2, but there is hope that the pandemic, with all its destructiveness, will deliver at least one service to humanity – it will provide humanity with a platform for the rapid development and production of a new type of vaccines.
The price of victory
Since the political noise in the media has convinced everyone, even seemingly politicians themselves, that the development of the vaccine is just a matter of months, many are already raising questions about its availability. How much will the vaccine be, which may perhaps save millions of lives as well as the overall health of the global economy, cost? Society is quite unanimous and uncompromising in this regard: “We need the pill right now, and we need it free of charge!” It is important to keep in mind that there are tens of thousands of people standing behind each and every pill, who are dedicating their lives to the fundamental science, clinical trials, biotechnological production, as well as the endless efforts to coordinate every step with regulators – all of it for the sake of an extremely limited chance of success. If there is no reward for all these efforts commensurate with the value created, if, in case of success, these people are vilified for the desire to “profit off someone else’s grief,” then, we can forget about further breakthroughs in the field of pharmaceuticals.
No one will conjure up any “miracles”, working under the conditions of a low probability of success for decades on end under duress, for a pittance, and while castigated. Governments should be prepared to pay a pretty penny for the vaccine and the drugs to treat COVID-19, and the societies should be demanding not price slashing for the drug, but rather adequate prioritization of the health sector in the budget.
I will share a telling story about an American company called Achaogen. We started communicating in 2012; at that time, the United States was trying to stimulate the development of antibiotics with new mechanisms of action, and our fund was keeping an eye on the companies that were emerging in that particular field. At the time of making our acquaintance, the company had been in business for 10 years, and they had already received $200 million of government aid for the development of a breakthrough antibiotic “of the last choice”, that is to say, of a kind that should only be resorted to if no other drugs have worked.
There were three serious risks in this potential investment: first of all, the new mechanism of action is already a risk in itself; secondly, there was an extremely high standard for regulatory approval (it was not only necessary to show that the drug was not inferior to others but that it also drives the mortality rate down better than all of the other previously approved drugs); thirdly, there was no market in place for the drug at that time. “The super bacteria that our drug will be fighting has not yet been introduced,” – said the head of the company, – “However, we presume that by 2018-2020 it may appear as a result of the global abuse of antibiotics.”
It must be said, however, that the price for that new drug promised to be quite low. The drug, naturally, would be used in extraordinary cases, when all other drugs did not work, potentially only once in a lifetime for a small number of patients, and, most importantly, only and if such an epidemic were to ever even take place. And, what if it never happened?
We did not invest in their development. It is important to realize the fact that these risks are not getting reduced but rather multiplied: even if the drug kills the super bacteria in vitro, it would have to undergo an extremely complex, expensive and absolutely necessary clinical trial among humans, and after all that, in the highly doubtful event it “survives” to the point of regulators’ approval, it could enter the marketplace where no one is waiting for it and nobody is ready to pay for it.
I had followed Achaogen for a long time – saw the volume of investments in the company reaching approximately one billion dollars, saw it go public, saw its capitalization grow several times over and catch up with the volume of the invested capital, and so on. I kept wondering whether I had made a mistake. Then, in 2018 their drug got approved. In the first few months, the volume of their sales amounted to less than $1 million, and a few months later the company had declared bankruptcy.
Thus, the question arises of why is it that governments stockpile warheads and their “delivery systems” in order to ensure the safety of their citizens, constantly update the reserve ammunition and spare no money at all for the most cutting breakthrough technology, but don’t procure antibiotics and the latest vaccines for storing them alongside the weapons in the very same bunkers?
It would become a humongous and guaranteed target market, a high-powered incentive for research and development, and at the same time a guarantee of security for the population of the said countries. But bureaucrats are more accustomed to providing support to “altruistic” science instead of paying handsomely for ready-made drugs and vaccines to the “greedy” big pharma companies. As it was illustrated by the example of Achaogen, it is apparent, that perhaps, just maybe, it would have been worth for the governments to simply adequately pay for a few working drugs that would have been developed through private investments, instead of pumping billions of state aid money into dozens of such companies.
A special path
Up until recently, it did not matter where you got infected with COVID-19 or in which country you were hospitalized. Everyone was treated the same way everywhere; that is they weren’t treated at all. The only difference would have been in the comfort of your stay and the potential risks of catching additional infections. Old Hepatitis B, malaria, and HIV medications were used everywhere, a practice that, according to the most recent data, has turned out to not only be ineffective but often one that worsened clinical outcomes. However, a significant discrepancy in the treatment protocols in various countries of the world may be emerging in the upcoming months.
Tens of thousands of small biotechnological developers, as well as big pharmaceutical companies, have joined in the work on testing, and now on developing drugs for each stage of the disease, both in the United States and in Western Europe. Dozens of private companies are involved in the development of the vaccine.
In Russia, there is more than a dozen state research institutes as well as a few large private companies engaged in the battle against the epidemic. As it was to be expected, the state sector has failed to come up with innovations. At the beginning of the epidemic, in addition to exploding ventilators, the government-supplied, in a monopolized marketplace, PCR coronavirus tests with extremely low sensitivity, producing many false-negative results that contradicted the obviously difficult clinical picture. And, as far as the Russian vaccine goes, it was “successfully” tested at the largest state institute of epidemiology – the Gamalei Center, sans any hearings in the ethics committee and without waiting for the completion of pre-clinical studies. It was been tested directly on the staff, which was announced by the head of the center on a major state TV channel. There is, obviously, no trust at all for this type of study.
But then again, Russia does have something to present to the world. There are world-class products that are being actively developed in the private sector. There is a Russian publicly-traded company HSCI, that has developed serological antibody tests for SARS-CoV-2, and it has been openly demonstrating the results of its studies throughout all of the stages of the research and development via social media.
There are three candidates from Russia in the WHO global registry of vaccines under development, two of which have been under development by the previously referred to a private company, BIOCAD. However, this does not cancel out the fact that in Russia there are now thousands of small private sector developers in Russia because there is no venture investment market in place that would allow for these companies to appear and grow.
At the same time, Russia in fact does have the money for the procurement of innovative foreign drugs and vaccines, but it is not being allocated for these purposes. As a result, the Russian pharma market is tiny and of little interest to the foreign players. On top of that, it carries risks for the public companies in conjunction with the Western sanctions. What this amounts to is that Russians are about to get any innovative drugs from the USA and Western Europe, which account for 90% of all innovative developments in the world, any time soon.
And nobody is particularly eager to lend a helping hand to Russia, as the country does not fall into the category of the poorest ones. An object lesson here is Gilead, an American manufacturer of Remdesivir, which, as of today, is about the only drug available that has shown a weak yet still positive effect throughout the clinical trials. Gilead has published a list of 120 developing countries where it is prepared to send Remdesivir at reduced prices. Russia did not make the list.
The root of the problem is deprioritizing public health issues which translates into an extremely low ratio of healthcare spending to the national GDP. In Russia, this indicator is less than 5%, in Europe, it is about 9%, and in the USA, it is approximately 18%. The difference is drastic even in relative numbers, and, in absolute terms it is colossal.
The chronic lack of funding in the healthcare system is the reason that neither the venture investment sector nor the innovative pharmaceutical industry can be established in Russia. On top of that, all competition has been eradicated in the process of “optimization”, nationalization, and the efforts to “support domestic manufacturers” for many years. One should always keep in mind that any restriction on competition hits the patients first and hardest, not the “bad” companies.
As luck would have it, Russia still has a unique technological capacity. There are scientists who have been integrated into the global scientific agenda and are ready to join in the creation of the new Russian pharmaceutical industry. Nevertheless, in order to translate scientific achievements into real drugs, it is necessary to have a venture investment market in place, which will necessarily appear as soon as there is an increase in spending in medicine. Otherwise, one can forget about top-quality health care in Russia.
There is a bill under discussion today in Russia that would simplify the access of venture capital funds to state pension funds, which is one of the pivotal sources of funding for venture capital investments in the United States. It is possible that this new regulation will turn out to be an incentive for the establishment of a competitive venture capital market. In addition, thanks to the pandemic, the leadership of our country has finally started talking of the necessity to increase expenditure in the healthcare sector, and not just by a fraction of a percent, but exponentially, to bring it to the level of the European average.
Thus, let us hope that one result of the pandemic will be new technological platforms for combating epidemics, giving the healthcare sector a higher priority in governments’ budgets and in the expansion of the countries’ “battle readiness” capacity. May breakthrough biotechnical developments for mass healthcare be added to the stockpiles of indestructible weapons of mass destruction.
Authored by Anton Gopka, General Partner and Co-Founder of ATEM Capital Biotechnology Venture Fund