The search for new Covid drugs — and a researcher’s reason for optimism

David Fajgenbaum is a physician and scientist at the University of Pennsylvania. He is best known for his personal battle against Castleman Disease, which nearly killed him before he discovered a treatment that saved his life.

Now, however, Fajgenbaum’s research lab at Penn is now working to catalog and analyze drugs that might prove effective against Covid-19.

He recently joined STAT’s podcast, “The Readout LOUD,” to discuss that work and more. Excerpts of the conversation are below, lightly edited for clarity.

When the pandemic hit, your lab created the Corona Project, a database of drugs being used to treat Covid-19 patients. What’s the goal of this project?

The goal is to collect data on all of the various treatments that are being tried for Covid-19. So in one place you can find all drugs reported to be used for Covid-19.

We use that information and subjective qualitative data on whether drugs look promising or not to help to prioritize which drug should move forward to randomized controlled trials. Because you can’t determine if a drug works against Covid unless you’ve actually studied it in a well-designed large RCT, so we use this as an early place to get a sense for what looks promising. We provide that data to funders and then we also look to identify drugs that should move forward to trials.

So what kind of progress are you making on the second half of that goal, on actually testing these things out in a rigorous way?

So we made the data publicly available. It’s been accessed by, I think, 20,000 users at this stage. What we’re hearing is that drug makers are able to go there and get a sense for which drugs in their portfolio are being tried for Covid and they can use that as some kind of preliminary data to determine whether they want to move forward with the trial.

But we’re also being proactive. We’re not just trying to make it a resource. We’re actually working directly with the FDA to launch a large-scale trial. And so we’re in the early stages of putting together a large, randomized controlled trial of those most promising agents.

So the U.S. government has invested about $8 billion to find drugs for Covid. Most of that went to research into manufactured antibodies, according to a recent story in The New York Times. That’s less than half the money that was spent on vaccine development. The U.S. also lacks a centralized network of hospitals to run randomized clinical trials. Is the Biden administration proposing any changes?

We haven’t gotten too much clarity on on the specific changes that need to be made. We’re all aware of the shortcomings within our system. People say, you know, we don’t have one U.S. health care system. We have thousands of U.S. health care systems, all in one country.

But I’m hopeful, because on the second day of the Biden administration, there was an executive order specifically around the idea of advancing treatments through appropriate clinical trials. So we don’t have details yet on how, but we certainly have an early signal that there is interest.

In the early days of the pandemic, there was a lot of optimism for the antiviral Remdsivir. We’ve since learned that the drug only has a modest benefit for patients and it has not been shown to meaningfully improve survival. What are you thoughts about the potential for the next wave of novel antiviral treatments?

And as we dove through data on over 400 drugs given to now over 270,000 patients that are in our database, it’s become clear that we can’t just think about treating Covid with antivirals. There isn’t going to be one drug that works no matter what time in your disease course it’s going to be. And it’s actually already been shown that certain drugs are effective at certain time points. And some of those drugs that are effective at one time point are actually harmful if give it another time point.

So we haven’t mentioned hydroxychloroquine yet, which is probably for the best. But more recently there’s been a similar controversy stirred up over the parasitic drug ivermectin. Again, politics seem to be intruding into the debate a little bit here. What do we know or don’t know about the role that ivermectin might play in treating Covid?

There was a lot of excitement early on with hydroxychloroquine because there were large observational studies where a large number of patients got the drug and a large number of patients survived and did well. And so the assumption was that, oh, the drug helped those patients to do well. But actually, what we know from Covid is that the vast majority of people get infected with Covid will survive and will recover.

And so the same thing has happened here with ivermectin, where there’s been some really exciting and promising retrospective observational studies. There were actually a number of Latin American countries where large numbers of the population were given ivermectin. And then there were subsequent declines in the numbers of cases of patients in those particular cities. And again, the the assumption is made that it’s the drug that is actually improving outcomes. But we can’t make that assumption because there are other public health measures that can also cause your infection rates to go down, like social distancing and masking. And so you can’t just assume because people were taking it and the rates went down, that it’s the drug. And so that’s where you have to do large, randomized controlled trials.

There is a pre-print of a randomized controlled trial from Egypt that does suggest that there is a benefit of ivermectin, but it has not completed its peer review. And we need to see these sort of results in multiple studies.

When you look ahead six months or even a year from now, what do you think the landscape of Covid drugs will look like once we’ve had more data to actually make decisions? Are you optimistic that that new treatments will be available, that we’ll have discovered the virtues of older treatments that might help?

When the pandemic first started, I was very optimistic that there were going to be a number of drugs that would be helpful because there were some really nice early data that suggested that. And then over the summer, I became really pessimistic as a number of large trials came out and didn’t show benefit from some of the early drugs that we thought were really going to be effective. But I would say I’m becoming a lot more optimistic right now as I look to the future.

And that’s because their drugs like fluvoxamine, which is an obsessive-compulsive disorder drug, drugs like baricitinib developed for RA [rheumatoid arthritis] and colchicine for gout that actually have shown benefit in randomized controlled trials, were waiting for the really big trials to make us feel totally confident in the results. But there are drugs coming down the pipeline and understanding, timing, and the fact that a drug that might be helpful at one stage could be harmful to another is really informing the way we do these trials.

So I’m actually quite optimistic about where we’ll be looking at in five months. As I look to the future, I can’t help but think to myself, how can we learn from this Covid experience? I mean, over 400 drugs have been repurposed. We’ve proven that we can repurpose and we’ve proven that we can also systematically track it in a very short period of time. And I’m hopeful that as a society and as a medical system, we think to ourselves, OK, we’ve got 2500 drugs already approved for something. How many other diseases could those drugs be helpful for?

This is a lightly edited transcript from a recent episode of STAT’s biotech podcast, “The Readout LOUD.” Like it? Consider subscribing to hear every episode.