Remember human embryonic stem (hES) cells? We don’t hear much about them anymore. And so I was surprised to see an application…
On June 2, JAMA (the Journal of the American Medical Association) held a Q+A for the media with Dr. Anthony Fauci, director of the NIAID, accessible here. JAMA Editor Dr. Howard Bauchner frequently interviews leaders in the quest to understand and combat COVID-19. The webinar series has been a huge help to the science journalism community.
Dr. Fauci was considerably more upbeat in early June than he was on a JAMA webinar March 23, soon after he was present for a White House press briefing at which more than 10 unmasked people standing close to each other addressed more than 10 journalists on matters of public health and the pandemic. At that JAMA webinar, Dr. Fauci explained the vaccine timetable based on how things were done in the past, and predicted we’d have one in 12 to 18 months. He said, then, that there’s “no vaccine in the immediate future, which tells us we need to rely on public health measures.”
But overlapping and collapsing the traditional stages of vaccine and drug development – preclinical (non-human animals and cells), phase 1 clinical trial (safety), phase 2 (safety and efficacy in small numbers), and phase 3 (efficacy in large numbers) – was already becoming the catalyst behind the accelerated timetable of creating vaccines against SARS-CoV-2.
Here’s the vaccine part of the June 2 Q+A, my comments in parentheses.
Howard Bauchner: Can you tell us about the first phase 3 clinical trial for a vaccine?
Anthony Fauci: It’s going to be a randomized, placebo-controlled trial of the first of the vaccine candidates, which is the Moderna mRNA vaccine that was developed at the NIH Vaccine Research Center. They’ve now done the phase 1 study, and the company started phase 2 a few days ago. We’re preparing the sites now for the phase 3 trial, both internationally and nationally but predominately nationally. It will have 30,000 people. It’s going to be a big trial because we want to get as many data points as we can.
Very soon after or even simultaneously, the AstraZeneca candidate
that was developed in the UK based on work done at the University of Oxford is going to be very closely aligned in time with the Moderna study. (AstraZeneca AZD1222 candidate is a recombinant adenovirus now being tested on 10,260 people in the UK in a phase 2/3 clinical trial following 1,000 people given the vaccine in the phase 1 study. Developers foresee possible availability by September.)
Some other studies are going to start one to two months from now as we get towards the end of summer. We will have an array of 4 or 5 trials I’m aware of and am either directly or indirectly involved in, either in development or in providing some of the clinical support for the sites being used to do the clinical trials.
HB: What have we learned from the phase 2 Moderna trial?
AF: The phase 2 trial had a few hundred people and was a safety and immunogenicity trial. But the business end of it all will be the phase 3 trial that will start the first week in July.
HB: How long will it be to see efficacy?
AF: Requiring 30,000 people to see efficacy is based on estimates. Data will accrue as the study goes on to see if those individuals are seeing enough disease. It isn’t the duration of the trial (that’s important) if it happens to be in a situation with a lot of infections. But if you go in and you have dribs and drabs of infection, even though 30,000 people are in the combined placebo and experimental groups, it could take months and months and months to get an answer. But if you start phase 3 and a month or two into it get in an area that’s been highly vaccinated with a big outburst and surge of cases, you can get your answer pretty quickly.
HB: How diverse is the group in the phase 3 trial in terms of age, sex, and ethnicity? Or is it focused on healthy younger people?
AF: The participants are predominantly 18 to 55, but there also will be those who are elderly and those who have underlying conditions and co-morbidities. It’s going to be the entire spectrum.
HB: Are you optimistic? You wrote a Viewpoint a few years ago about acceleration in vaccine development. At that point even you didn’t see this particular pandemic coming and that we would be able to move to a phase 3 trial in 6 months. So are you optimistic?
AF: Yes, I’m cautiously optimistic that with the multiple candidates with different platforms, that we’re going to have a vaccine with a degree of efficacy that would make it deployable. The reason I think so is that one makes a good immune response against this virus. The overwhelming majority of people recover. Obviously the deaths are profound, over 105,000, but still the majority of people make an immune response that clears the virus. And that tells us that if the body can mount an immune response and clear the virus in natural infection, that’s a pretty good proof of concept that you’ll have an immune response against a vaccine.
However, you can never guarantee that you’re going to get an efficacious vaccine. I’m concerned more about the durability of the response than I am about whether you get a protective response. When you recover from one of the several benign coronaviruses that causes the common cold, the durability of protection is only a year or less, as opposed to some of the other infections where you can have 10, 15, or 20 years of protection.
HB: In the fall, a good vaccine candidate won’t be needed for 30,000 people, but for 20 million or 50 million. What happens with production of that vaccine?
AF: That’s what’s going on right now, and it’s something very unique in vaccine development. The companies and the federal government are doing this “at risk.” That means not at risk to the patient for safety, and not at risk for the scientific integrity, but at risk for the investment.
We are going to start manufacturing doses of the vaccines way before we even know that the vaccines work. The predictions and projections and statistical analyses indicate that we may know if a vaccine is efficacious or not by maybe November or December. Which means that by that time we hopefully would have close to 100 million doses and by the beginning of 2021 a couple of hundred million doses. So it isn’t as if we’re going to make the vaccine and show it is effective and then have to wait a year to rev up to millions and millions and millions of doses. That’s going to be done while we’re testing the vaccines. That’s what at risk means.
I’m very happy to admit that I likely have been wrong in my conservative views of when a COVID-19 vaccine would be available, basing my opinion, here at DNA Science and at Genetic Literacy Project, on the history of vaccine development.
The efforts to invent, test, and eventually distribute one or more vaccines against SARS-CoV-2 are truly unprecedented. Mea culpa.