Three weeks, two drug trials: An update on the Therapeutics Accelerator with Trevor Mundel

Trevor Mundel, President of the Bill & Melinda Gates Foundation's Global Health program, discusses the first trials funded through the Therapeutics Accelerator. The Accelerator was established three weeks ago to develop drugs and other antiviral treatments.

It’s been about three weeks since the foundation announced the COVID-19 Therapeutics Accelerator. What progress has been made?

Yes. There’s been a lot of progress. First, we’ve seen additional funding coming into the Accelerator from a range of governments, philanthropies and individuals. This speaks to the importance we all see in moving as quickly as possible to find solutions to prevent or lessen the impact of the disease moving forward. New donors include the U.K. Government, Chan Zuckerberg Initiative, and the artist and philanthropist Madonna.

We’re also seeing progress on the science. There are two trials starting pretty much simultaneously, using chloroquine and a drug with a slightly different structure, hydroxychloroquine. Now, you may have heard of the WHO SOLIDARITY Trial that was announced two weeks ago, which will look at chloroquine as a treatment for people who are sick, to see if it shortens the duration of their sickness. The two Accelerator studies are looking instead at prophylaxis — stopping people exposed to the virus from getting sick.

From the existing data, which need validation in a trial, it looks like hydroxychloroquine could be a good agent for prophylaxis. It actually blocks the entry of the virus into the cell, so the hypothesis makes a lot of sense: if you have the drug in your system and you get exposed, you won’t let the virus get into your cells and you won’t get onset of disease. That is what the trials are aimed at showing.

The first study is looking at post-exposure prevention, so giving the drug to somebody who’s been in close contact with someone infected with the virus. We want to see if it can stop the infection or shorten the length of it. That study going to be run by the University of Washington School of Medicine, in collaboration with NYU’s School of Medicine and it will be done in Western Washington and in New York, since those are two hotspots right now. It’s being funded by the foundation through the Accelerator.

It has now begun and will involve around 2000 individuals in an 8 week trial. Close contacts of ill patients will be treated for 2 weeks and closely followed for evidence of infection. We’ll likely have the read-out of this study in early summer.

The second study is investigating pre-exposure prophylaxis, just like what we do for HIV — the equivalent of PrEP but for coronavirus. This would be for highly at-risk individuals: front-line healthcare workers, first responders and others who work in situations where they’re coming in contact with people.

This trial will be done by the University of Oxford and is being funded by Wellcome through the Accelerator. It will be a much longer study — two years.

There are two pieces to the Accelerator. One is drugs, and the other is biologics.

The drugs piece is basically small molecules. These are things that could easily be synthesized in a lab. Chloroquine’s a small molecule. It exists. We know how to make it, we know how to synthesize it quickly, and we can scale it up.

Biologics are things like a lot of the rheumatoid arthritis drugs that you see advertised on TV in the United States. They’re not synthesized in the same way. They’re made using living organisms that produce proteins. Which is another way of saying, they’re not very easy to make, and they’re not going to be as fast. We won’t have them for this outbreak, but we’re still looking at them because we don’t know how long this will last. If COVID-19 becomes endemic, we might need them. And again, they could be a good thing for health workers and people who are on the front lines to use.

That’s right. We’re not expecting to find a 100-percent-effective solution right off the bat. HIV is the paradigm that we’ve used in other viral situations: We treat it with a mixture of drugs. The same is true for TB. The pan-TB regimen is three drugs.

That’s why the Accelerator is looking to identify a shortlist of about 50–100 FDA-approved drugs, and then narrow this down to a few that could be scaled up. And what this will look like is, first trying to use individual drugs, and then of course combinations of those individual drugs.

It looks more and more likely that there will be a combination that is more beneficial. But the difficulty in drug discovery is that building combinations is a body of work; to reach the right combination takes time and a lot of data.

But even with a combination of drugs, there probably won’t just be one. There will be different segments of patients. The combination more suited to a severely ill patient probably won’t be the same as the combination that you want to go into your outpatient, those mild to moderately ill individuals who are transmitting in the community. The target product profile differs.

This means all the things the Accelerator looks at could be useful in different ways.