Following an initial outbreak in China, the novel coronavirus spread rapidly around the world. As of June 2020, over 7.2 million people worldwide have been affected, with a death toll of more than 410,000. These numbers continue to grow. Our guest today is Richard H. Kaszynski, who works as an emergency physician in Tokyo. As he treats coronavirus patients in Japan, he continues to conduct drug research as part of a healthcare innovation group out of Stanford University. Kaszynski spoke about an existing drug that is a candidate to treat COVID-19, as well as the importance of international cooperation in conducting clinical drug trials.

When we see coronavirus patients or when we see COVID-19 patients, a lot of them will present with symptoms that closely mimic the common cold. This is especially true for younger patients in their twenties or thirties, maybe in their early forties. They will come in here with a sore throat, maybe a little bit of a cough, slight fever. I think where COVID-19 differs significantly from seasonal influenza or the common cold, is that the progression, at least from what we have seen, is relatively rapid. Especially in patients who are in their fifties, sixties, seventies, eighties, basically the high risk demographic groups that we encounter, the progression is fairly rapid. And of course with that, as the age increases, we are seeing more dismal outcomes such as increased deaths as well.

An effective cure for COVID-19 has yet to be developed. Research is being conducted in countries around the world into the efficacy of existing medicines in fighting the virus. One of the drugs seen as a potential candidate is Favipiravir, which was originally developed to treat new strains of influenza. In Japan, it is known by the brand name Avigan. Kaszynski was one of the first doctors to recognize the drug's potential. However, the drug has yet to be approved for use in the treatment of the novel coronavirus. Recently, an observational study was conducted involving around 3,000 patients. Kaszynski himself has administered the drug to coronavirus patients in a medical setting.

From my personal experience in using the drug on patients and administering the drug, I think for the most part, I would say that in mild to moderate cases, the drug has been tremendously well tolerated and effective. There are a small fraction of patients that I have come across who have... You know, we administer the drug thinking that, okay, it should work on this patient, but for whatever reason, it does not, and the patient symptoms progress. This would be a ballpark figure because we do not have the exact data to show this, but I would be pretty comfortable to say that, you know, at least 80%, 70 to 80% of patients have shown very good results after taking the drug.

The idea to use Favipiravir to treat COVID-19 stemmed from Kaszynski's work in the Democratic Republic of the Congo, where he has been a senior medical advisor to the government since 2018. He had been conducting research into Favipiravir in an area struggling with an Ebola epidemic. Then in January 2020, he began hearing about a novel corona strain spreading from Wuhan, China. Learning that it shared a common enzyme with the Ebola virus, he began to see Favipiravir as a potential candidate to treat COVID-19.

But the virus began to spread more rapidly than he had anticipated. Cases in Japan began increasing dramatically in March. On April 7th, Japan declared a state of emergency. Some hospitals found themselves over capacity with COVID-19 patients.

Medical sites are truly in a critical situation.

Japanese doctors were struggling with how to best treat patients with mild symptoms.

Roughly 80% of the patients who contract the virus will be in a mild to moderate state of disease, meaning that these patients do not require any sort of hospitalization. What we want to do is we want to try to prevent this 80% from progressing to a stage that would require hospitalization. And right now, there is no drug out there that we could actually use in an outpatient setting. If you do have influenza, we do not say, okay, you have influenza so let us admit you to the ICU and get you treated. For the most part we say, okay, so you have influenza. What we want you to do is go home and take these pills. And then we would say, you know, get plenty of rest, take plenty of fluids, go home. And then if the situation gets worse, please come back.

If we have a drug in Japan that is approved for use, that could be used in the outpatient setting, then theoretically we could do the same thing.

Kaszynski says that one of the advantages of Favipiravir is that it comes in pill form. In other words, people with mild symptoms can take the drug themselves, without the help of doctors or nurses.

I think at the end of the day, we are not only preventing the progression of disease in that individual. If we are able to shorten the duration in which that there is ongoing viral shedding from that patient, then in essence, we are able to prevent secondary infections as well. So those are two benefits. The third benefit that an outpatient-based treatment would work is on the social level. So in the medical infrastructure level. If we are able to prevent the progression of disease in the individuals, and we are able to prevent the spread of disease in the community, then at the end of the day, this all trickles down into reducing the burden that we are imposing upon our health care facilities.

Kaszynski also points out that a drug's form is closely related to its medical costs.

When we look at the overall cost for a drug, you have to look at the exact cost for the drug itself. And of course the peripheral costs. So the peripheral costs would be, for example, how much is it going to cost to store the drug? How much is it going to cost to actually administer the drug? Is it a drug that you have to have a member of the medical staff come in and use a needle to inject you with? Or is it something that I can just come in and say, okay, here are a few pills, please take these at home according to this regimen? I think when we are looking at the pure costs associated with the peripherals. It is just very different for injectable solutions versus orally administered drugs.

In his work treating Ebola in the Democratic Republic of the Congo, Kaszynski felt the high cost of injectable solutions had the potential to be a strain on the country's financial resources.

The other drugs are administered... these are injectable solutions. Therefore they require certain types of management. Cold chain management that is not really required for pills like Favipiravir. We like Favipiravir on that level. We are looking at a situation where it is generally hot throughout the year. A lot of the places that we are active in, a lot of the regions that we are active in, are frequently encountering blackouts.

One of the lessons that we've learned in Africa is, if you're helping to combat something, a novel threat to humanity like Ebola, what is the point of saving people from Ebola if we are going to bankrupt that economy or if we going to bankrupt that local society with these new drugs and have people starving to death in six months or 12 months down the road. So, what we are looking at is the big picture.

A drug's potential side effects are always an important consideration. Some studies have shown that the drug has the potential to disturb the development of embryos.

Absolutely the last thing that we want to do with this drug is administer it to a woman of childbearing age who happened to be pregnant but did not know about it. Or even in males, the drug is also included in your sperm. So, you cannot actively have intercourse while you are taking this drug. So I think a proper informed consent is imperative. So it is our job to make sure that every single patient that we administered the drug to is properly informed. And I think that is the best way to mitigate those risks.

Kaszynski is currently working to build an international network to conduct clinical drug trials in the fight against the pandemic. In order to find an effective treatment in the face of the rapid spread of the virus, he believes international cooperation is crucial. In May, universities and government ministries from six countries answered his call. Among them, England has begun clinical studies of Favipiravir. Observational studies of the drug are underway in Japan, but the evidence is still insufficient to determine the drug's efficacy. A Japanese pharmaceutical company is also looking into the drug. However, with less than 100 participants, it's considered a small-scale study.

What we are trying to do with this international cooperation, international alliance is just trying to find a way to conduct these clinical trials in a more rapid fashion, because if we are doing same clinical trials the way we do this during peace time, it's going to take years before the drug is going to be approved for use. And we simply don't have that time. And so what we are trying to do is establish this alliance of like-minded individuals to try to help tackle this issue.

So for example, if we are doing a study at Stanford with a 120 patients. And maybe if they are doing a similar study in the UK and then Belgium, and again, let's say they are doing studies with 150 patients and another 100 patients. And all of these patients add up and what would originally amount to each individual institution conducting their own small-scale study, which has a slightly lower level of evidence, becomes empowered by this collaboration. The general consensus is that the drug is effective, does seem to be effective.

The only problem with the manner in which the drug is being administered in Japan is that it is being done on an observational basis. So it is an observational study, meaning that there is no proper control. Because again, it is not a proper RCT. Meaning that the argument could be made that well, you know, these patients were on the road to recovery anyway. So we cannot say for certain that it was because the patient took the drug that the patient survived.

RCT, or Randomized Controlled Trial, randomly assigns participants into two groups, one of which acts as a control group.

If it was a proper control, we could say, okay, one group gets the drug, the other group gets a placebo. And at the end of the day, we compare the results and say, yeah, in fact the Favipiravir group did display better clinical outcomes. The side effects were X, Y, Z, and we could actually do a proper comparison. As a result of that, your conditions may worsen. This is a risk that the patients have to take as well. Because of those sacrifices, a lot of patients are benefiting. It is not something that we take lightly at all.

This is not going to be the last pandemic that humanity faces. And there will be future pandemics. And I think one of the areas that we have not been prepared enough is the scrutiny, scientific scrutiny, and also the processes involved for approvals of drugs during pandemic times. This has never been adequately addressed. And I think that is what we are trying to start.

One study Kaszynski and his colleagues are conducting is scheduled to be completed in August. He says that international coordination is needed to overcome this crisis.

I think that humanity will triumph over this pandemic. It is going to take time and it is going to take the cooperation of everybody. Your personal actions have that much more of a ripple effect on the greater society and on the planetary level, in certain cases. My only request would be really to just try to work together. And this is at the community level, the family level, and also the international level, to help overcome this issue.