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Each week, Health Affairs Editor-in-Chief Alan Weil brings you in-depth conversations with leading researchers and influencers shaping the big ideas in health policy and the health care industry.
A Health Podyssey goes beyond the pages of the health policy journal Health Affairs to tell stories behind the research and share policy implications. Learn how academics and economists frame their research questions and journey to the intersection of health, health care, and policy. Health policy nerds rejoice! This podcast is for you.
00;00;00;00 - 00;00;28;01
Alan Weil
Hello and welcome to “A Health Podyssey”. I'm your host, Alan Weil. As the COVID-19 pandemic emerged, the biopharmaceutical sector quickly went to work on vaccines and treatments. Finding drugs to treat a rapidly emerging and spreading disease requires a combination of developing and testing new drugs, while also studying existing drugs to see if they're effective against the new virus.
00;00;28;25 - 00;00;59;14
Alan Weil
Now, the stakes for getting the science right are extremely high. Early enthusiasm for drugs like hydroxychloroquine, which was ultimately demonstrated to be completely ineffective against COVID, can cost lives and feed into conspiracy theories regarding the motivations of pharmaceutical companies. So how should we approach studying existing drugs when a new disease emerges? So-called drug repurposing? That is the topic of today's episode of “A Health Podyssey”.
00;01;00;09 - 00;01;24;04
Alan Weil
I'm here with Jennifer Kao, assistant professor at the UCLA Anderson School of Management. Dr. Kao and coauthors published a paper in the March 2023 issue of Health Affairs examining drug repurposing for COVID-19 treatments during the pandemic. They found testing of a large number of existing drugs, which evolved into more testing of de novo drugs as the pandemic progressed.
00;01;24;16 - 00;01;30;28
Alan Weil
We'll discuss what they learned about drug repurposing in our discussion today. Dr. Cao, welcome to the program.
00;01;31;12 - 00;01;34;24
Dr. Jennifer Kao
Thank you for having me, Alan. I'm delighted to be speaking with you today.
00;01;34;29 - 00;02;00;23
Alan Weil
So your paper covers a really interesting topic. There was so much attention to vaccine development, and the heroic efforts to get vaccine out to people quickly, much less focus on drug development for treatment and particularly drug repurposing. So why don't we start by just if you could give our listeners a little bit more of a sense of what it means when we talk about drug repurposing?
00;02;01;07 - 00;02;25;26
Dr. Jennifer Kao
So this is an important question because any discussion of drug development must be grounded in an understanding of how drugs are regulated in the United States. So in the United States, drugs are developed and approved for a specific condition. And drug repurposing is the use of a drug previously approved for one condition to treat an entirely different condition.
00;02;26;19 - 00;02;37;07
Dr. Jennifer Kao
And a large share of drugs are maybe great candidates for drug repurposing. So one study estimates that 90% of approved drugs have multiple therapeutic uses.
00;02;37;20 - 00;03;00;10
Alan Weil
And we hear sometimes about off label use. So drugs are approved for one thing, but they may be used for others with different, under a different regulatory scheme because that's not on label. Why is it, it may seem obvious, but why is it that it's worth looking at repurposing? And why might it actually be better for us to use a repurposed drug than a new drug?
00;03;00;16 - 00;03;28;03
Dr. Jennifer Kao
Absolutely. So policy makers and researchers are so excited about drug repurposing because it's believed to offer several key advantages that allow patients faster access to safe and effective treatments. So I'll mention three of them briefly. First, repurposed drugs are often considered to be relatively safe. These drugs have already undergone prior clinical studies and regulatory scrutiny for their approved condition.
00;03;28;12 - 00;03;59;21
Dr. Jennifer Kao
Second, repurposed drugs may be able to come to market more quickly. Trial sponsors may leverage their previous experience with a drug. They may also be able to skip early stage safety trials. And finally, repurposed drugs may increase patient access to affordable medicines. As Rena Conti and her coauthors have previously described, repurposing generics may increase the set of available treatments to patients at lower cost.
00;04;00;16 - 00;04;23;25
Alan Weil
So if you can find a drug that works that already exists, that does seem like it has significant benefits. Let's go into your findings. What did you find regarding efforts to identify existing drugs that could be effective against COVID-19? How many of these drugs were identified? What did they do with them? Just give us a sense of what this ecosystem looks like.
00;04;24;00 - 00;04;50;13
Dr. Jennifer Kao
So luckily for us, as researchers in the US, trial sponsors must register their clinical trials in a publicly available trial registry. And so using the data from this trial registry, we find that over a two year period there were around 485 clinical trials testing treatments for COVID-19. And of these, 44% tested at least one repurposed drug.
00;04;51;00 - 00;05;12;14
Alan Weil
There's a lot of activity going on. And let's just be clear, when you say you're starting a trial here, you mentioned earlier when it's a repurposed drug, some of the regulatory hurdles have already been overcome. And so you can sort of move into the field and say, let's figure out if this is going to work. Talk to me if you could about what these drugs were.
00;05;12;14 - 00;05;16;14
Alan Weil
What were folks looking for when they were considering repurposing?
00;05;16;15 - 00;05;47;13
Dr. Jennifer Kao
So typically we found that the repurposed drugs were actually originally approved for a wide range of diseases. The repurposed drugs in our dataset were most commonly originally approved for infectious diseases or musculoskeletal issues. So one example is dexamethasone, which is an anti-inflammatory agent that was first approved in 1958 to treat rheumatoid arthritis. Now, at the time of our study, dexamethasone had been tested in nine trials for COVID-19.
00;05;48;01 - 00;06;16;22
Dr. Jennifer Kao
Now, moving on to trial drugs that were a little bit more surprising. Some drugs were originally approved to treat diseases that were much more distantly related to viral infections such as opioid dependance. An example of that might be Naltrexone, which was first approved in 1984 to treat opioid dependance. And during the pandemic, Naltrexone has been investigated for its ability to reduce fatigue and pain in individuals with COVID-19.
00;06;16;28 - 00;06;46;06
Alan Weil
So the idea here is that folks are looking for drugs that treat something related to the symptoms that we see associated with this emerging disease and, you know, you don't know if you don't try. So they're out there testing these out. You mentioned sort of the timing here. Can you say a little bit more about sort of speed to trial for the repurposed drugs relative to the de novo ones?
00;06;46;17 - 00;07;14;01
Dr. Jennifer Kao
When we look at the timing of these repurposing trials, we find that repurposing was a really important complement to de novo drug development. So in the first half of 2020, two-thirds of COVID-19 trials were testing repurposing drugs. However, as the pandemic progressed, the tide of research efforts really turned to de novo drug development. Between the third quarter of 2020 to the end of 2021,
00;07;14;10 - 00;07;39;11
Dr. Jennifer Kao
the share of trials testing at least one repurposing drug fell to 30%. And this trend is really consistent with the idea that in context where the rapid development of treatments is necessary, as it was in the pandemic, trial sponsors may first turn to repurposed drugs because they're likely to be a little bit more safe and have these shorter clinical development time.
00;07;39;29 - 00;08;13;15
Alan Weil
So you're describing sort of an ecosystem here of urgency and what can you do quickly? You can take drugs off the shelf that have already passed a safety profile, already have indications. You see if they'll work. In the meantime, you're trying to develop new drugs that might be effective, but that takes a little longer and those then begin to dominate, particularly because it seems in the end, none of the repurposed drugs ever ended up showing as much of a positive effect for people with COVID as the new ones.
00;08;13;16 - 00;08;14;05
Alan Weil
Is that right?
00;08;14;13 - 00;08;48;05
Dr. Jennifer Kao
Absolutely. And so this really raises a policy implication of this work, which is when we think about drug repurposing policies more broadly and the value of drug repurposing, we really need to make sure that we have policy that help balance that tradeoff between moving quickly and also maintaining high scientific standards. And while repurposing trials may demonstrate efficacy quickly, if these initial repurposing efforts are poorly conducted, they may not hold up to future or further scrutiny.
00;08;48;05 - 00;08;59;26
Dr. Jennifer Kao
And there are real costs to that. And this can include drug withdrawals which can shake public confidence and also early off label drug use that can lead to dangerous side effects.
00;09;00;09 - 00;09;23;28
Alan Weil
Yeah, this is such a critical issue. Because we're trying to be at the front edge of the science, each trial by itself adds to our knowledge, but it's a trial and people are eager, looking for answers and they may move faster than our confidence. But when there are no other options, they may feel like this is what they need to do.
00;09;24;07 - 00;09;55;00
Alan Weil
I'm so glad you mentioned the issue of the policy context. Of course, we're a policy journal, not a clinical journal. So I want to talk to you a little bit more about the policies that need to be in place so that we can benefit as much as possible from these repurposed drugs. We'll have that conversation after we take a short break.
00;09;55;00 - 00;10;27;21
Alan Weil
And we're back. I'm speaking with Dr. Jennifer Cao about drug repurposing during the COVID-19 pandemic. Before the break, we learned a lot about how many of these drugs were tried out and how it evolved from looking at repurposed drugs to newer drugs. But as we entered the break, we started discussing the policy environment. And before we get into some of the policy issues, I think it would be useful if you talked about one of the findings in the study that we haven't covered yet, which is about who's sponsoring these trials.
00;10;28;02 - 00;10;37;10
Alan Weil
That seems really relevant. It's not cheap to put on a trial and the findings here are interesting. Can you say a little more about who conducted these trials?
00;10;37;17 - 00;11;05;26
Dr. Jennifer Kao
The findings really highlight the unique and economic incentives that shape drug repurposing and drug innovation more generally. So to keep things simple, I'll discuss the COVID trials sponsored by industry and academic institutions. When we first look at de novo trials or trials testing new drugs, we find that industry sponsored 60% of these trials, whereas academia sponsored just 13%.
00;11;06;10 - 00;11;27;04
Dr. Jennifer Kao
The percentages are almost reversed when we look at repurposed drug trials. Industry sponsored just 17% of repurposed drug trials and academia sponsored 60%. Academia plays an even larger role of We focused our analysis on trials testing repurposed drugs with generic competition.
00;11;27;14 - 00;12;05;15
Alan Weil
Okay, so this sort of seems like a perfect story of economic incentives, right? The pharmaceutical industry has a greater stake in a new drug. And maybe also, correct me if I'm wrong, access to the resources to undertake the study of a new drug which requires more testing. The academic institutions are less driven, presumably by the incentives associated with new drug development, although some are, but they're very interested in trying to find ways to move quickly with the repurposed drugs.
00;12;06;02 - 00;12;21;11
Alan Weil
If I'm getting that story right, what does that tell us? You've mentioned sort of the economic ecosystem. What does that tell us about what kind of incentive system we need if we're going to maximize the potential benefits associated with repurposed drugs?
00;12;21;17 - 00;12;52;11
Dr. Jennifer Kao
Our findings indicate that if we think that the regulatory approval of repurposed drugs provides more benefits than, for example, off label drug prescribing, then we need to support institutions that can help shepherd academics from successful clinical trials to formal regulatory approval. As an example for this, this can take the form of funding contract research organizations with special expert expertise and academic-led repurposing efforts.
00;12;52;22 - 00;13;16;04
Dr. Jennifer Kao
Alternatively, this can take the form of government initiatives that are directly funding repurposing trials, and there's been a growth of these initiatives in the U.S. and in Europe in recent years, largely in response to this concern about the dearth of economic incentives. And it will be really exciting to see and follow the results of these efforts.
00;13;16;17 - 00;13;42;13
Alan Weil
So are there other aspects of the regulatory environment that you'd want to bring up here in addition to sort of the basic financial incentives? I realize those are all tied to the regulatory environment. We made a quick allusion to off label use. Maybe you'd like to talk a little bit more about that or just more broadly, when you think about the regulatory environment, what comes to your mind as salient?
00;13;42;29 - 00;14;21;03
Dr. Jennifer Kao
The most important thing to know about the current regulatory environment for repurposing is that it creates a whole host of complex incentives and disincentives for quickly identifying effective treatments, new treatments of approved drugs. So we mentioned the incentives already. For example, earlier, being able to skip early stage clinical trials. And in addition to that, what incentive might be that if a manufacturer attempts an additional approval for the new condition, the manufacturer will be able to legally promote the use of that drug for that condition.
00;14;21;03 - 00;14;52;13
Dr. Jennifer Kao
At the same time, the regulatory environment creates a bunch of disincentives for firms to invest in high quality repurposing trials to support regulatory approval, for example, off label drug use or the use of a drug to treat a condition that is different from what it's approved for is legal and widespread. And while off label drug use may certainly allow patients faster access to new treatments, there are certainly potentially limitations and costs.
00;14;52;24 - 00;15;07;06
Dr. Jennifer Kao
And as researchers and policymakers, we are still really working to understand the overall benefits and costs of the current regulatory environment. It's a really complex issue, but that's what makes it so interesting to investigate.
00;15;07;18 - 00;15;40;07
Alan Weil
Yeah, which brings me to a question. You're in a school of management, which is not the place that many of our authors sit for their academic positions. And I wonder if that affects sort of the types of questions you ask. So, as I read this study, various questions come to my mind. But when you think about the next, out of the work you've done here, what questions it raises for you that you could imagine going in deeper or studying for your next topic, I wonder if you could say a little bit about where it leads you.
00;15;40;19 - 00;16;07;16
Dr. Jennifer Kao
Absolutely. So my background in policy and my current position within a business school context very much informs my work. I always think about, does the research that I'm doing speak to both types of audiences. And I'm also very excited and motivated by the fact that health care innovation is very much influenced by regulation and health care innovation is also very much driven in many respects by the private sector.
00;16;07;24 - 00;16;34;29
Dr. Jennifer Kao
Understanding the interactions between regulation and firm decision making is really important for thinking about how we might design policies that can ultimately lead to better health care outcomes. And when I think about my future research, I'm really excited to really get a better understanding of the role that drug repurposing can play because if done correctly, there are really a lot of economic benefits, health care benefits to be had.
00;16;35;04 - 00;17;02;07
Alan Weil
Well, that's so interesting because really at the end of reading your paper, you come away with this sense that the incentives for the private sector to pursue drug repurposing are probably inadequate. I realize that there are lots of trade offs here, but given the differences that you saw between who initiated the trials for repurposed relative to de novo drugs, it certainly suggests that there's something to look at here.
00;17;03;03 - 00;17;31;11
Alan Weil
And given the high cost of drug development and discovery, anything we can do to bring those costs down seems worthwhile. And yet we also have to be really cautious here because early results, I realize not all drug repurposing will occur in the context of a pandemic, but early results really can be very hard to take back and that can lead to very negative consequences as well.
00;17;31;11 - 00;17;40;24
Alan Weil
So we're balancing some very thorny public policy and public health issues here. I guess that's why there will be no shortage of things for you to study in the future.
00;17;41;19 - 00;18;17;00
Dr. Jennifer Kao
Absolutely. And we really found that given, you know, the pandemic, there were a lot of really interesting questions to be studied within that context. And one of the features of the pandemic is to really understand to what extent can drug repurposing really step up in a situation where there is this huge demand for effective treatments fairly quickly. And so understanding the trajectory of the response has been really informative for thinking about the role of drug repurposing, particularly in relation to de novo drug development.
00;18;17;00 - 00;18;25;20
Alan Weil
Well, Dr. Cao, thank you so much for the research you've done here, the contribution to our understanding of drug development and for being my guest today on “A Health Podyssey”.
00;18;26;04 - 00;18;31;16
Dr. Jennifer Kao
Thank you so much. It was a real pleasure.