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Infectious disease

Merdad Parsey on building a case for remdesivir amid the coronavirus pandemic

Gilead’s Chief Medical Officer talks about the challenges of clinical design in the time of COVID-19

by Asher Mullard, special to C&EN
April 10, 2020

 

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Credit: Gilead
Gilead's CMO Merdad Parsey

Merdad Parsey joined Gilead Sciences as chief medical officer in November 2019. Within weeks, he learned that an infectious disease crisis was brewing in China. By mid January it was clear that the killer pathogen was a coronavirus, and Parsey found himself at the center of the biggest pandemic in a century. He has been working flat out ever since to spearhead the development of the company’s antiviral remdesivir. Although Gilead first developed the RNA polymerase inhibitor for Ebola, it also has preclinical activity against coronaviruses. First results from this drug in COVID-19 are due within weeks. He spoke with C&EN about building an evidence base for COVID-19 drugs during the SARS-CoV-2 emergency, and realistic expectations for the first round of agents. Questions and responses were edited for length and clarity.

C&EN has made this story and all of its coverage of the coronavirus epidemic freely available during the outbreak to keep the public informed. To support our journalism, become a member of ACS or sign up for C&EN's weekly newsletter.

What were your key priorities when you first started thinking about getting remdesivir to patients?

The biggest thing for us was that COVID-19 was localized in China initially. There were not a lot of cases outside of China. So at first we were really working through how to get into trials in China as quickly as possible. Fortunately, we were able to connect with investigators there. And that was what we could do most efficiently: ship drugs and placebo to investigators there to do the trials.

These investigators are now running two trials in China, in 450 severe patients and in 300 mild or moderate patients. How have you since broadened the global trial landscape for remdesivir?

We’ve also opened up what we call simple trials. These are fairly light-touch studies. In [2,400] severely ill patients, we are studying for either 5 days or 10 days of therapy; and in [1,600] moderately ill patients, we are studying for 5 days and 10 days of treatment, or standard of care. We’ve worked rapidly to get as many sites open for these as we can.

We’ve also been working with the NIAID, who are doing a study in [400] hospitalized patients in the US and Europe. And there is the World Health Organization’s Solidarity trial, an umbrella trial that we are supplying drugs to as well.

And we have compassionate use studies.

WHO’s Solidarity trial, launched in March, is comparing the efficacy of four different therapeutic approaches: remdesivir, the antimalarials hydroxychloroquine or chloroquine, the HIV drugs lopinavir plus ritonavir, and these HIV drugs combined with the immunomodulatory agent interferon-β1a. They may yet add other drugs to this international study. What is the value of adaptive mega-trials like Solidarity, versus testing these drugs individually?

When we first started looking at setting up trials in China, there weren’t a lot of other studies going on. By the time we were up and running in mid February, it seemed like there were 10s if not 100s of other competing trials. This is not necessarily a problem, because no one really knows which medications will work. But it does create this dynamic where it would be ideal if we could understand whether one thing works before going on to test the next. That’s a challenge in this environment, with so many studies ongoing. And we’re not seeing the quality of data being generated that I think we would all like.

Umbrella trials [that test multiple drugs in a single disease] can be viewed as analogues to large-basket trials in oncology [that test a single targeted drug in related cancer settings]. There are pros and cons to these. And one of the cons is that the more questions you ask, the harder it is to answer any one question.

When patients are more precious—in that it takes longer to enroll patients—then being focused on one question at a time is in some ways easier. When there are a lot of patients that are sick all at once, you might be able to ask a broader set of questions simultaneously because you can enroll so many patients.

It’s hard. Everyone is really trying to answer questions as quickly as possible. On the one hand, you want to be coordinated. On the other hand, you don’t want to spend too much time getting coordinated because the pace of this thing is so rapid. Everyone’s doing their best.

When do you expect to be able to provide initial results for remdesivir?

We’ve been telling everyone the latter part of April for at least 2 months now. And we’re on track for that.

We have some data that have come in from our compassionate-use studies that I would say are observational in nature, and we are putting those data together and would like to submit those soon. So that could be publicly available sooner. But, the latter half of April for that larger, more robust, trial data. [These data, in 53 patients, have now been published in the New England Journal of Medicine.]

Everyone is really trying to answer questions as quickly as possible. On the one hand, you want to be coordinated. On the other hand, you don’t want to spend too much time getting coordinated because the pace of this thing is so rapid.

The history of antiviral research is riddled with clinical-trial setbacks, including the failure of remdesivir to prove beneficial in treating Ebola. Even the use of the FDA-approved antiviral Tamiflu for flu is controversial. What are your expectations for remdesivir and the other leading antivirals in COVID-19, and are these aligned with the general public’s expectations?

I’ve been doing this for a long time, and I think this is a very difficult situation. Even when you have the opportunity to design molecules for specific pathogens, it’s hard to be successful. And the timing of drug use can matter a lot. So there can be and probably will be a mismatch between what we’re going to be able to demonstrate and what the public’s expectations are.

But I’m doing my best to stay out of that prediction game, and will let the data speak.

Globally, over 180 COVID-19 trials are now recruiting patients. If you reflect on how this has played out, is there a need for a more active, coordinated, drug-development triage system?

I haven’t really had much time to reflect over the past months. What a novel concept.

I am prone to wanting to prioritize things. But what I’m seeing is that, right now, everyone is able to enroll quickly. This is a terrible statement on the state of things, but we are able to move down that list fairly quickly.

And no one’s prepared for this. Not everyone has stockpiles of investigational agents ready. So some agents are lower down on the priority list just for practical reasons: there is no drug supply yet.

I’ll add that from day one, we’ve had fairly broad outreach to other companies, in terms of anticipating the need for manufacturing help, and things like that. And more recently, there has been a group of R&D folks from around industry who are on telecoms usually once or twice a week to discuss COVID-19. Everyone’s been incredibly collaborative. We are all working through the different options and trying to help each other out. It’s really heartening.

UPDATE

This story was updated on April 10, 2020, to include a reference to Gilead's now published compassionate use data for remdesivir.

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