Anthony Fauci, the director of the National Institute for Allergy and Infectious Diseases, has seen the photos of bars packed with mask-less patrons. He was not impressed.
That said, these days, Fauci sees reason for cautious optimism about Moderna’s vaccine, and others. The idea of having a vaccine by the end of the year is “aspirational, but it’s certainly doable,” he told STAT in a wide-ranging interview.
One of the most visible faces of the U.S. response to the coronavirus pandemic, the NIAID director also acknowledged the world will have limited data on the new vaccines when they are deployed, and may have to balance the need to save lives with the possibility of some adverse events.
A transcript of the interview has been lightly edited for length and clarity.
A lot of states are moving to open up really quickly, trying to get their economies back in gear. We’ve seeing pictures of crowds on beaches and in other settings; many people aren’t wearing masks. Are you worried that we’re setting ourselves up for a boomerang effect in the next few weeks?
I certainly have sensitivity for the need of the public to start getting to some form of normalization, given that we’ve been through more than three months of a very difficult time. But it’s a big country and the dynamics of the outbreak are different from one part of the country to another. If people want to get out, they’ve really got to gauge it with the level of the outbreak in their particular area.
When I see a situation where there is a region, a state, a city, a county where there’s a considerable amount of viral activity there, and you see people crowding around bars — and there were several pictures of that, that was quite striking over the last couple of days — or on boardwalks, where they’re very, very close to each other, I do get concerned.
Let’s talk about vaccines. In a recent interview with the Financial Times Merck CEO Ken Frazier effectively questioned the assertion — which you have made — that we could have Covid-19 vaccines within 12 to 18 months. Merck has a ton of experience developing vaccines. Are you at all worried that expectations for the timeline to vaccines have been set too high?
I am not really very concerned about the timetable of this for the following reasons.
The general trend on the part of the pharmaceutical companies, because of the enormous investment that goes into the development of a vaccine, is that you don’t go to the next step until you’re fairly certain that the step you’re in is going to be successful. The other thing is you don’t start manufacturing anything until you have a pretty good idea that you have a successful efficacy signal. That protracts out the time frame. But what we’re doing is something that’s called developing “at risk.”
What it means is that at the same time you’re finishing your Phase 1 trial, you’re preparing your Phase 3 trial sites, which is very expensive, and then you’re starting to manufacture the vaccine even before you know it works. All of that cuts months off.
We’re now completing the Phase 1 [with the Moderna vaccine]. The initial data look very promising from the neutralizing antibody standpoint. And so they’re planning to start the Phase 3 in the first week or so of July. Not only with the Moderna vaccine, but also very likely with the AstraZeneca vaccine. And then as we get later into the summer, we’ll get the Johnson & Johnson in clinical trials.
You need a few months at least of having vaccinated individuals getting exposed. So let’s say it’s July, August, September, October. By November, you should have an efficacy signal.
If you do and you’re already manufacturing doses, by December and January, if you’re lucky and if in fact it is effective, you can have a significant number of doses available by the end of the year, the beginning of 2021. So I think it’s aspirational, but it’s certainly doable.
The only thing that’s the big unknown to me is that, is it going to be effective? I think we could do it within the time frame that I’ve outlined. But there’s no guarantee that it’s going to be effective.
Let’s talk a bit about what you’ve seen so far in terms of data. When Moderna recently released some the information on the vaccine they are developing with NIAID, they showed neutralizing antibodies in eight people. Are there more data? And what are the antibody levels like? Because they didn’t give us any kind of scale against which we could assess what they were saying.
I know. I didn’t like that. What we would have preferred to do, quite frankly, is to wait until we had the data from the entire Phase 1 — which I hear is quite similar to the data that they showed — and publish it in a reputable journal and show all the data. But the company, when they looked at the data, as all companies do, they said, wow, this is exciting. Let’s put out a press release.
The thing that made everyone be cautiously optimistic is that we didn’t just see binding antibody. It was clearly antibody that was neutralizing live virus, at levels that you would predict would be protective — if in fact neutralizing antibody, which is a reasonable assumption, is going to be a correlate of immunity.
Have you been at all concerned about adverse events? They had some Grade 3s. [Grade 3 adverse events are serious, but not considered life-threatening.]
At the high dose. Of course, whenever you get adverse events at high doses, you’re hoping that you can get the protective effect that you want at a dose that’s considerably less than that. And it looks like we can. [Moderna has discontinued study of the highest dose.]
What about what you’re seeing about the other vaccines in the clinic already? Do you think things are looking good for multiple vaccines to come through?
Well, the Oxford University vaccine [developed in partnership with AstraZeneca], the data in the animals, you know, some of the animals got infected. They didn’t get sick. I would have liked to have had protection against infection. But then again, it depends on what you’re looking for with the vaccine. That vaccine doesn’t look like it’s a knockout for protecting against infection, but it might be really very good at protecting against disease. So I withhold judgment on that.
You’re asking me an opinion of things, but there’s still little data. The Pfizer one is very similar to Moderna’s. It’s an mRNA vaccine. I’m sure that Pfizer is going to get results that are as good as the Moderna vaccine. There’s no reason to believe one is going to be any different than the other.
What I like about the whole thing is that there are multiple candidates that we’re involved with. It just feels good to be directly or indirectly involved in four or five candidates, to do it in a way that I refer to as sort of harmonized, where you come to an agreement, which we did, that we’re going to do things where the trial protocols will be quite similar, where the laboratory tests that we’re going to ask for are going to be quite similar, so that you can extrapolate results from one study to another.
Now, why is that important? If one vaccine proves efficacy in a clinical trial and another vaccine is behind it but it’s getting the same correlate of immunity you could bridge data and facilitate the approval of the second and the third one based on the efficacy of the first one.
You said vaccine could start to be administered in late December or January. Is that the time frame President Trump is looking for? It sounds like he’s hoping for something sooner.
I think that the president and the administration would be really very happy if we had a vaccine that we could deploy by the end of this year.
Does the president talk to you about the vaccine work often?
We used to have task force meetings every single day, including Saturday and Sunday, and about 75% of the time after the task force meeting we’d meet with the president. So I was meeting with him four times a week back, a month or so ago.
But as you probably noticed, that the task force meetings have not occurred as often lately. And certainly my meetings with the president have been dramatically decreased.
With such a compressed timeline for testing the vaccines, how much do you think we’re actually going to know about them before we start to deploy them? If you’re only getting a few months worth of data, we won’t know much, if anything, about the durability of the protection. And, you know, we may not have a ton of information about efficacy or safety.
So when you design a clinical trial, there are a certain number of events that will give you a definitive answer as to whether or not your vaccine is effective. That is set in stone. So we’re not going to declare efficacy or even begin to think about efficacy or not until we reach that predetermine statistically sound number of infections that either occurred and/or were prevented. I mean, whether we do the trial over 10 years, or we do it over four months, the endpoint is still the same. It’s certainly statistically significant difference. So I don’t worry about that.
On durability, you’re absolutely correct. We’re not going to know what the durability is. But we’re going to have to live with that. The first thing we’re interested in is: If we vaccinate you in the late summer, early fall, are you protected through that fall, that winter and then going into the spring? If the answer is yes, wonderful. Then we’ll worry about durability.
And in terms of safety, you are facing the same thing. I mean, obviously, the concern with a vaccine, with a virus like this, is what are you going to get enhancing effect, [where the vaccine actually makes some recipients develop worse illness if they contract the infection]. We’ve seen it with a couple of other viruses that we had reasonably good vaccines against, dengue and respiratory syncytial virus.
We’ve designed the Phase 3 trial, to very carefully look at safety, even more so than is done in a regular trial.
Is a trial of 30,000 people large enough to see that kind of a signal if it exists?
Yeah, I think so. But then again, someone would say, appropriately, but what happens when you give it to 5 million people?
Or 5 billion?
And then if that’s the case, then you’ve got to balance — you balance the lives saved from the vaccine with the enhanced detrimental effect. So if for everyone that has enhanced illness, you save a thousand lives, I’ll take that, right?
There’s a lot of interest in developing vaccine as quickly as possible, but there’s also a lot of concern about the speed at which this is being undertaken. Should there be major adverse events associated with use of these vaccines, it could really damage trust in vaccination in general. Is that something you are worrying about?
Yes, I am.
But I just realized that I have to phone into an Operation Warp Speed meeting. I’m already late. I’ll talk to you later.