Georgia Today: The Emory University lab behind what could be a gamechanging COVID-19 pill

Drug company Merck is awaiting word on its emergency use authorization application for its recently announced drug molnupiravir. If approved, the anti-viral drug developed at a lab at Emory University could become the first-ever pill to treat COVID-19. The latest Georgia Today podcast examines the journey that led to this potential breakthrough and its connection to Emory.

RELATED: In the race for a COVID-19 pill, a little lab plays a big role

TRANSCRIPT

Steve Fennessy: You're listening to Georgia Today. I'm Steve Fennessy. On the podcast this week, another leap forward in the battle to curb the coronavirus pandemic: Drugmaker Merck announced that an experimental pill it was developing could cut the risk of COVID-19 hospitalizations and deaths by half. Dr. Anthony Fauci called Merck's preliminary results for molnupiravir good news.

Dr. Anthony Fauci: It's an orally administered drug that's really very important. It was compared to a placebo. In the placebo group, there were eight deaths and in the treatment drug group there were zero deaths.

Steve Fennessy: If health regulators authorize it for use, it would become the first pill shown to successfully treat COVID-19. My guest on the podcast has been following the Emory University scientists behind the drug's development. Patrick Adams is an Atlanta-based journalist who writes about the pharmaceutical industry. He's written about molnupiravir for the New York Times and how it came to be. So when we're talking about molnupiravir, it sounds like it's this kind of brand-new invention, this brand-new creation, a miracle of the pharmaceutical industry. But in fact, the origins of this drug actually go back a number of years, right?

Patrick Adams: That's correct. This drug has been in development for some years. Molnupiravir is a nucleoside analog. It's a — it's a class of antivirals that inhibits the replication of RNA.

News tape: 4WWL: It works like Tamiflu, the antiviral for influenza viruses. Take the pill at home when you catch the virus, and Merck says it keeps the coronavirus from replicating so you have a lower viral load. One being used now is remdesivir, but it's given by I.V. in a hospital setting.

News tape: PBS NewsHour, Dr Nahid Bhadelia: If you can give something by mouth quickly after diagnosis, you're improving the access, you're keeping more people from getting into the hospitals and you may also reduce the time that people are contagious, which could reduce transmission as well. So an oral antiviral has been the missing piece in a way that we respond to this pandemic.

Steve Fennessy: I recall in the early 2000s, Emory, you know, made huge headlines because of the development of an AIDS cocktail drug. And I think that the university made something like $525 million — some insane amount of money — for developing this AIDS cocktail, which has since become instrumental in fighting HIV infections. And some of the same people who were involved in the development of that are also involved, right, in the development of molnupiravir?

Patrick Adams: That's correct. That was a huge development in academic drug discovery.

News tape: Mayo Clinic, Dr. Stacey Rizza: In the last 20 years, we've gone from people taking multiple medicines with lots of side effects to the majority of my patients with HIV now take a single pill a day that's a combination of medicines co-formulated — one pill a day that's extremely well tolerated and completely suppresses their virus.

Patrick Adams: So in 2003, the drug Emtriva was approved for HIV, and that drug was developed by researchers at Emory, Dennis Liotta and Raymond Schinazi, and Woo-Baeg Choi, I should say as well.

Steve Fennessy: We hear about, you know, private laboratories investing, you know, millions and millions of dollars in developing drugs. But then we also hear about academic institutions, research institutions that are also doing the same thing. So how does all this collaboration happen?

Patrick Adams: Most people, when they think of where drugs come from, it's from large pharmaceutical drug makers, right? You know, market forces really shape how drug discovery happens, and that skews investments that they make in R&D toward diseases with, you know, the highest financial returns and away from those with low or negligible commercial potential for diseases, you know, neglected diseases. And at one time, that was HIV and other diseases like malaria and tuberculosis.

Steve Fennessy: You mentioned this term neglected diseases. What's a neglected disease?

Patrick Adams: Usually it characterizes a disease that affects a lot of people around the world, mostly poor people, doesn't result in a lot of death, more sickness and disability, and because of the population that it affects, does not have a large commercial return. So companies are unlikely to invest in the research and development that is required to bring that drug to market. And so therefore, you have a group of diseases for which there are very few treatments available.

Steve Fennessy: So Dennis Liotta is one of the people who helped discover sort of these this drug cocktail to combat HIV infections in the early 2000s. What was his sort of philosophy when they reap the rewards of that in terms of developing new drugs?

Patrick Adams: Denis Liotta, after he invented Emtriva along with collaborators and sold that drug to the pharmaceutical industry, was able to use royalties that he made from that drug to invest in research around neglected diseases. I mean, he wanted to to do something that would change the paradigm, as he put it at the time. They came up with a new business plan, and that was DRIVE. DRIVE is a acronym for Drug Innovation Ventures at Emory. And it's a nonprofit, wholly owned subsidiary of Emory University. But it's a little different than an academic drug discovery center that you might think of when you think of a university. This is something that has a bit more autonomy and that allowed them to pursue drugs for neglected diseases and strictly those resulting from an infection with an RNA virus. And the reason they focused on that was that they have this really deep expertize in virology at Emory. They had a portfolio that included at least three drugs that I know of. They had one for hepatitis B, they had one for rhino and intero viruses that was in development. And then they had what was known as EIDD-2801.

Steve Fennessy: That's a mouthful.

Patrick Adams: Which became molnupiravir, exactly.

Steve Fennessy: Another mouthful.

Patrick Adams: That's right. And that was initially for a biodefense threat called Venezuelan equine encephalitis virus, a virus that had been actually weaponized by both the United States and the Soviet Union and was considered a threat. So there was defense money to pursue development of that drug as a countermeasure.

Steve Fennessy: Is there anything more you can tell us about Dennis Liotta himself? What is it that sort of motivates him and people like him? Because a lot of times they're they're chasing drugs that never pan out. You know, there's a lot of dead ends here.

Patrick Adams: Soon after Dennis came to Emory in the late Seventies, AIDS became a problem and was killing lots and lots of people. And I think that he wanted to do something about it, that he wanted to use his skill set to try to intervene. I mean, you know, it's pretty incredible what that laboratory and he and his colleagues managed to do in terms of curbing AIDS. But with the development of two of the most widely prescribed AIDS drugs that there are, that made possible a once-daily — the first once-daily pill for HIV.

Steve Fennessy: AIDS was, by and large, a death sentence. And now an HIV infection is not necessarily a death sentence at all if you have the right medication.

Patrick Adams: That's absolutely right. For people who had access to those anti-retrovirals, it was transformed from what was a death sentence to a manageable chronic disease. And it was really, I think, compassion, and I really believe that he wanted to address diseases of the poor with, you know, the resources that he had in the wake of those successes. And he tried to do that.

Steve Fennessy: We have this active research and they're developing these drugs and then the pandemic comes along and they have molnupiravir. So I'm curious, at what point did they say, Hey, this could be something that would actually help fight coronavirus?

Patrick Adams: Yeah, with colleagues at Georgia State University, you know, when when SARS-CoV-2 emerged, they quickly redirected research to look at that, and they subsequently published in Nature Microbiology, a journal. The first demonstration that molnupiravir is active against that virus in an animal model. So they established the proof of concept that this treatment completely suppresses the virus transmission, which is an important finding.

Steve Fennessy: So they see the potential and molnupiravir. What does it need to do to sort of like, say, OK, this is something that we need outside help with to see if this has a real prospects?

Patrick Adams: DRIVE is unique in that, unlike I think most academic drug discovery centers, it can take a compound pretty far along this development pipeline and de-risk it. As they like to say, for a biotech or pharmaceutical company to come along and say, we're willing to make the investment to take this across what's known as the Valley of Death. That's a euphemism for part of the development pipeline that's very costly. That involves clinical trials, things that a small group at at a university just can't do doesn't have the resources or in many cases, the expertise or the infrastructure to do. You know, you can have trials with thousands of patients, certainly. Obviously, the larger the number, the better. In order to see potential side effects, they partner with researchers all over the world to perform the studies that can move this along. And so that's for the biotech comes in. That's what in this case, Ridgeback did for DRIVE. So Ridgeback is a biotech company that licensed the drug from DRIVE and took it to the next stage of development for a pharmaceutical company like Merck to come along and decide to purchase it.

Steve Fennessy: Ridgeback licenses the drug from DRIVE. What's Merck's involvement here?

Patrick Adams: With Merck, you were able to take the compound to the next phase —Phase Three — and they showed in this in this latest trial, that they've halted, a 50% reduction in risk for hospitalization and death. It's a huge finding.

Steve Fennessy: Why did they halt it? Why would you halt it?

Patrick Adams: That's because they decided that it would be unethical to continue giving patients the placebo when the drug is found to be as effective as it is now.

News tape: 11Alive: The drug owned by drug maker Merck, has shown to be effective in humans during Phase Three of its clinical trial results, so encouraging it stopped its trial early to seek emergency FDA approval of the drug.

Steve Fennessy: And does the clinical trial indicate if there are side effects to taking this?

Patrick Adams: You know, they found more side effects actually in the placebo group, which indicates that perhaps this group is getting COVID-19 and feeling the effects of that. So it seems right now that there are not significant side effects to the peer review.

Steve Fennessy: There were concerns early on in the development that there were some potential toxicity issues with it. What were they and how have those been addressed? Is that still a concern to some degree?

Patrick Adams: Early on, I knew that there was a concern that molnupiravir might be mutagenic, meaning that it that it could cause a mutation to change in the DNA of a cell. That could manifest in something like a birth deformity in pregnant women. Now my understanding — and we don't have access to the Merck data right now — is that had they seen something, they would not have continued the trial. And I think Merck is known for abandoning drugs that that have been shown to be dangerous at all. So I think there is some confidence in Merck.

Steve Fennessy: So the development of molnupiravir has not been without a little bit of controversy, right? I recall that there was some whistleblower complaint that was at last year, earlier this year or something or last year, I guess.

Patrick Adams: That's right. Rick Bright, who is the former director of BARDA, which stands for the Biomedical Advanced Research and Development Authority, blew the whistle on, you know what he felt was cronyism in pursuit of government funding for drugs, including for molnupiravir. And in that case, he wrote that the CEO of Emory Institute for Drug Development in DRIVE, George Painter, had requested funding without having first shown human safety data. I know that he had published some emails in his whistleblower complaint. And I'm not sure that his allegations have been independently corroborated. But my understanding is that DRIVE was still looking for money to — to continue development and believed in the drug and felt that through rich bank, they were able to request this money. Now, whether that was improper? I really don't know.

Steve Fennessy:Next, how molnupiravir might be used to treat diseases beyond just COVID-19. This is Georgia Today.

[BREAK]

Steve Fennessy: You're listening to Georgia Today. I'm Steve Fennessy. Joining me is freelance journalist Patrick Adams, who's been covering Emory's role in the development of a potential COVID-19 drug called molnupiravir. The federal government, just like it did — it placed orders, you know, with all kinds of vaccine makers early on in the pandemic —so it’d have a number of vaccines, a significant number in case others didn't work out. Have they placed orders for molnupiravir?

Patrick Adams: They have, yeah. In September, BARDA purchased 1.7 million courses of the regimen for, I think, was $1.2 billion.

Steve Fennessy: They're paying, they're paying much more than a dollar a pill.

Patrick Adams: They're paying a lot more. And 699 more than a dollar a pill. I think it's still unclear, you know, what the price for a five-day regimen will be. I think that the government will certainly negotiate that. But yeah, I mean, because, you know, federal funding did support the development of this. I'm sure the government will have a say.

News tape: Dr. Scott Gottlieb: Merck is going to start filing the data and it's just a question of how long the FDA's drug review division takes to review this. I suspect they won't be as fast as the vaccine division has been. So this could be a one- to two-month review. You could see an emergency use authorization within one to two months.

Steve Fennessy: Patrick, take out your crystal ball. OK, so we we've got this pandemic; we’re almost two years into it now, and by all accounts, this is going to become an endemic disease, much like the flu. So let's say that the FDA approves molnupiravir as a treatment for COVID-19. How does this potentially sort of change the scope of the disease for us?

Patrick Adams: You know, I've heard all along from experts that, you know, while it's critical and what a miracle that we have the vaccines that we do, it's also important to have orally available drug, while as we have seen, vaccines can prevent infection. Many people still are infected and don't have access to vaccines.

Steve Fennessy: And are resistant to vaccines, and that's an interesting sort of wrinkle with this, right?

Patrick Adams: That's true. The skepticism around the vaccines has been, I think, really unfortunate development and one that I don't think that health authorities fully anticipated to the extent that it has happened. But it shows how important it is that we also have this intervention as well.

News tape: PBS NewsHour, Dr Nahid Bhadelia: Compared to monoclonal antibodies, this is something that you can take by mouth, and the use of monoclonal has been limited is because it requires intravenous infusion and that requires a clinic.

Steve Fennessy: What does all this mean for Emory, for DRIVE, for the neglected diseases that Dennis Liotta and his colleagues, you know, have been devoting much of their professional life to developing drugs for?

Patrick Adams: I spoke with Dr. Liotta the other day. He mentioned that they have been working over the past several months to expand DRIVE into new therapeutic areas, including oncology and neurodegenerative diseases. I expect we'll see a larger DRIVE. I mean, more activity and probably more collaborations with universities like Vanderbilt, like UNC, elsewhere. And you know, we have a lot more funding going into antiviral drug development today as a result of this pandemic. The government has invested, I believe, $3 billion as part of the American Rescue Act for antiviral drug development.

Dr. Anthony Fauci: And it aims to catalyze the development of new medicines to combat COVID-19. And importantly, to prepare for other pandemic threats.

Patrick Adams: That funding will be available to groups like DRIVE and other academic drug discovery centers. To for that, antiviral drug development is something that is, you know, relatively young in drug development as a whole. There's such an interesting space. I mean, I think the development of molnupiravir is obviously huge. Should it be authorized and should it be approved? I do think that the the business model is something we should pay attention to. And I don't think doctors Liotta or Painter are saying that DRIVE is the only way to do this, of course, or that it's going to work everywhere. But is it something that might yield additional therapeutics down the road that we might need? Yeah, perhaps. You know, we've seen a decline in innovation in the pharmaceutical industry at large. No major pharmaceutical companies. In response to that, academic drug discovery centers have stepped up and tried tried to fill the gap. And some have been able to do some things. You know, there have been other really important drugs to come out of academia, but to do that in a sustainable way is very challenging, and I think DRIVE may be one answer to that.

Steve Fennessy: This is a potential game changer in a pandemic, the likes of which we haven't seen in 100 years. And so if you have potentially a pill that you can take after being infected, that reduces your chance of being hospitalized or dying, and you're one of the guys behind the development of this. That's — that's amazing.

Patrick Adams: I have to say he he's one of the most soft-spoken people I've ever met. For all of the success that he and his colleagues have had together, he really is — is amazingly just humble about it. I think he's very excited about the possibility for molnupiravir to really have an impact on this pandemic, absolutely.

Steve Fennessy: To what degree was the pandemic sort of an accelerant for this kind of innovation or would have happened anyway?

Patrick Adams: I think it did. I think that it was a bit of luck, maybe. But I think one lesson from this is that we really do need these broadly acting antivirals, things that can target a bunch of different things. The traditional approach to antiviral drug discovery had been sort of “one bug, one drug.” But I think increasingly the the holy grail of antiviral drug discovery is finding something that's really broadly active and that's what they may have in molnupiravir. It's really too early to say whether it actually is something that will be useful against other viruses, but I think there's a great hope that it might be.

Steve Fennessy: I've been speaking with Patrick Adams. Thanks to him for sharing his reporting. Enthusiasm is growing about molnupiravir as potential as both the COVID-19 drug and as a big moneymaker. One recent estimate projects sales could reach $5 billion next year if the drug is approved. For more Georgia Today, go to GPB.org. Georgia Today is a production of Georgia Public Broadcasting. Subscribe to our show anywhere you get podcasts. And don't forget to leave us a review on Apple. Jess Mador produced this episode. Our engineer is Alex Word. Thanks for listening. See you next week!