More than fifteen hundred clinical trials are underway worldwide related to the coronavirus disease. Many of these experiments are focused on developing new drugs and therapies to treat patients. Along with public health measures, those are an important line of defense against COVID-19 until a vaccine is created. In KNAU’s weekly update on the science of COVID-19, Melissa Sevigny spoke with infectious disease expert Dr. Paul Keim about what’s promising and what’s not.
Melissa Sevigny: Tell me what’s going on in the world of drug development?
Paul Keim: So COVID-19, we’re just at the beginning of this whole process of trying to identify drugs and therapies…. One of the strategies that is being explored in the short term is repurposing other drugs. The number one drug therapy right now is remdesivir. Remdesivir is a drug that attacks the virus, the COVID-19 virus, as it’s replicating its genome. Its genome is made out of RNA, unlike the human genome that’s is made out of DNA, so it’s a little bit unusual. But there are lots of RNA viruses out there, and Ebola is another example. Ebola was actually a virus remdesivir was tested on. It didn’t work as well as they hoped, and didn’t work as well as some of the other therapeutics, so it was pretty much shelved. But now it’s been brought back. It had already gone through some different phases of human trials, Phase 1 and into Phase 2, so we knew a lot about its toxicity, we knew about doses, how much you give to people and how long it lasts in this system. So this repurposing of a former drug is seen as a shortcut for getting a drug into the clinics to treat COVID-19.
Now there’s another example of drug that’s been repurposed that’s become infamous and notorious. That’s hydroxychloroquine…. In the laboratory, in these in vitro tests where we look at virus replication in the laboratory in cell cultures, it works. From there, some physicians actually took it into clinical trials, and one of the most well-publicized ones was in Marcé, France. In that study, it was pretty small, it wasn’t really a well-designed study in the fact that it didn’t have good control groups… That study’s been discredited but other studies have been initiated…and the clinical trials will be trying to show whether first off is there a toxic side effect of this, and secondly does it do any good?
And all of these treatments, it’s really too soon to know how well they’ll work or if they’re going to work?
Yeah, and again the hydroxychloroquine is a lesson to everybody. There were anecdotal stories about how that drug was working, but they weren’t well controlled, so it turns out that drug does not work out as well as people thought when they first started talking about it. With these new drugs it’ll be the same thing, we need to go through Phase 1, Phase 2, Phase 3 trials. Phase 1 they will try to establish that these drugs are safe…and in Phase 2 you increase the number of people involved in those and hopefully get up into the hundreds. Then Phase 3 is where we really establish what the drug is good for, what type of COVID-19. You have people on ventilators, you have people with mild colds. When do you use a drug? How does it help improve the severity of disease in all those different situations?
Under normal circumstances how long does that process usually take?
It can take decades… When we’re talking about what we call pre-clinical trials, which are where we’re testing these in the laboratory or in animal studies, those studies can take several years by themselves, and most of the drugs we try in the pre-clinical studies never make it into humans. So that Phase 1, or first human study, becomes really important. They’re very expensive. To take a new drug from start to finish is certainly in the billions of dollars.
What’s the failure rate? How many of those are likely to result in an effective treatment?
The failure rate is very high, certainly better than 90 percent. Part of that is because if you get a good therapy than the ones that are only half as good don’t make it. Right now the best practice we have is the remdesivir, so everything will be compared against that, and if they don’t do better than remdesivir, they’re not going to make it through the FDA approval process. I’ll make a prediction that in two years we’ll have things much better than remdesivir and in fact remdesivir wouldn’t have made it through the process. So it’s the best thing we have right now, but it’s not a magic wand, it’s not going to just cure you instantly.
Do you think there’s concern in the scientific community that the pressure of this situation is rushing the process of getting drugs to the market, or are their safeguards in place to make sure the science is good?
I think that is a big fear. We’ve already seen that happen with some of the testing. The FDA relaxed the regulations and there was a plethora of bad tests came onto the market, and now they’re having to pull back. It’s just a matter of speed verses quality. There are safeguards, but we also see that there’s politics involved, too. Pressure to get something done, that is political, right? In some cases that pressure is good because it makes sure everybody’s attention is on the problem, on the other hand it can mean people will take shortcuts.
What’s the main takeaway you want people to know about drug development?
I guess the bottom line here is, for the next few months, maybe 6 months to 12 months, the major thing we have against this disease is hygiene and behavior. Especially as governmental regulations shift people still need to be very, very careful from their behavior, because it’s not going to be solved in the short term. I can tell you, my personal mantra is: “don’t get sick, get vaccinated, and then get on an airplane and go someplace fun.” That’s absolutely what I’m going to do.
Paul Keim, thank you so much for speaking with me today.
You’re very welcome, Melissa.