In this week’s episode, we speak with Andrew Dunn from Business Insider to discuss the COVID vaccine timetable; who are the players, who are the front runners, and when will a vaccine be made available to the general public.


Jeffrey Freedman: Hello and welcome to the RP HealthCast by RooneyPartners. I am your host Jeffrey Freedman.

With the election cycle in full swing, the pandemic is obviously front and center of both parties’ talking points. But one of the only things that both sides can agree on is the need for a vaccine. The unfortunate part of these vaccine discovery discussions is the potential for turning science-based decisions into political ones. I think as a country or even globally, we believe a safe and effective vaccine is in our near future. But knowing that these vaccines have been safely vetted and not rushed to the market for someone’s personal agenda is really what concerns us. Even after getting a vaccine approved, we have drug makers, we have our local and federal governments, healthcare insurers, even the militaries, they all get to need to collaborate on mass production, collaborate on creating a fair and orderly distribution plan, and then even collaborate to convince the public that it is safe and necessary for everyone to get vaccinated. The speed that all this is happening is unprecedented and there are so many different players involved. It is really tough to keep track of who is getting close to product approval and with different companies approaching these vaccines in different ways, it is hard to tell if one therapy is going to be better than the other or work differently on different people. To make sense to of all this we have our guest this week, Andrew Dunn. Andrew is a healthcare reporter at Business Insider covering the pharmaceutical and biotech industries. Since the pandemic began Andrew has been reporting exclusively on coronavirus vaccines and therapies. His stories have taken an in-depth look at vaccine discovery and clinical trials for these potential therapies. Andrew, it is great to have you back.

Andrew: Thanks for having me, Jeff. I am happy to be here.

Jeffrey: Let us just get right into it. What is going on with what you write about? Every day, we either hear a different story from a different person. Either the vaccine is coming as early as the end of the month or sometimes we hear we are not going to see one until next summer. Your job here today with us is to separate fact from fiction. Is it just wishful thinking or is it hyperbole for political gain? Let us start with how many vaccines are currently under development and how many are in the final stages? Who are they?

Andrew: Overall, there is a ton of work going on around the globe. There are well over two hundred vaccine research projects ongoing. Obviously, two hundred is a lot to keep track of. A lot fewer are in human testing so that is a sort of the first barrier I think of is, are these vaccines on lab benches still being optimized, still being tested in test tubes and beakers, and animal models, that type of stuff, or have they actually entered the clinic and started human testing. When you think about human testing, there are a few dozen. The number keeps going up every week but maybe thirty to thirty-five vaccine candidates that had started human testing. Obviously, the basic steps of the drug development vaccine development process you have phase one testing small numbers, making sure it is healthy, and the healthy people making sure it is relatively safe. Then you start phase two, phase three testing, where you go from dozens of people to hundreds to thousands of volunteers. Eventually these phase three trials, these are the ones we are really focused on right now in our effectiveness driven study. They are actually looking to see does this vaccine actually prevents infection, does it prevent disease. Actually, it answers the question do these shots work? As far as phase three vaccines, there are about half a dozen across the globe that are in this final stage of testing. Most of them centered around the U.S. Some doing global trials. With that as sort of the way of the land then I think it is probably helpful to get a little bit into who are the front runners, who are the ones we always keep hearing about these companies, and where they are at currently. There are sort of three leading efforts for these past few months that have been generating most of the tension and sort of leading the pack, those are Moderna, Pfizer, and AstraZeneca. Moderna, there were the first to start human testing back in March. They started their phase three study in late July. Again, this is a study that is recruiting thirty thousand volunteers, randomizing them between Placebo, and getting two doses of Moderna’s vaccine, and then following them up to see when there is a meaningful difference between that Placebo group and the ones getting Moderna’s vaccine. The same thing is going on with Pfizer and Beyond Tech. They have a very similar timeline, they also started phase three trial in late July. They expanded that trial from thirty thousand to forty-four thousand volunteers. They are also looking at pretty similar endpoints as far as what they hope to see from their vaccine. The main difference here between Pfizer and Moderna, as far as the timeline expectations their CEOs have put out, Pfizer’s CEO has been a little more bullish. He said over and over for the past few weeks that he expects results in October, showing it is effective, which is by far the most aggressive timeline out there. Speaking with Stéphane Bancel, who is the CEO of Moderna, he sees a base case scenario of November for results. He calls it unlikely but potentially possible to see results for Moderna in October. But again, base case scenario in November and he says, if the virus starts to spread less, if we see less cases within the people in the study, it could extend out until December as kind of his worst-case scenario.

Jeffrey: You name the top three or the three that have been in the news every day. Obviously, we have J&J Janssen, we also have Novavax, so that is five, right? You also said that there are a hundred ninety-five other companies working on vaccines. It is hard to believe that these frontrunners could be out by the end of the year. We are hoping the entire world gets vaccinated within a year from that or two years from that. Are two hundred vaccines even necessary? Is it physically irresponsible? But I guess that is a question for another day. But with two hundred different vaccines going on and certainly the top four or five, how can they be different? What is so different? Is one going to be better than the other? I mean, is one going to be better for a certain demographic, like one better for the elderly versus pediatric. Do they even know anything about pediatrics? Or across ethnic or gendered lines?

Andrew: Yes, it is a great question. I think that is what on everyone’s mind. If you have two hundred vaccine candidates or whatever the number is, how do you distinguish between these and prioritize them and actually craft a coherent plan on who gets what vaccine. I think a big part of this is waiting for the day that speaks for itself. Waiting for phase three results to be published with specific data and hopefully, some of those answers become self-evident as far as if we are talking about a subpopulation of the elderly, or particularly young people, or people with comorbidities. If you look at those individual subpopulations, is one vaccine just clearly better than the other? That would make some of these decisions a lot easier. If for whatever reason vaccine B works well in for the elderly let us make sure vaccine B goes to the elderly. People say unprecedented, it feels like every day around the pandemic but there is nothing I have seen like it or read about in the history books or in previous clips that compares to finding this balance of just the overwhelming urgency for an answer to this pandemic and getting something A.S.A.P. to people. When, whatever the number is, eight hundred, nine hundred, a thousand people are dying a day in the U.S. and around the globe. I think, we just passed the one million death marker. There is an outstanding urgency to get something as soon as possible when you see the calamity that is going on around us. At the same time, you want to make sure you get it right. You want to go through this rigorous scientific process that requires time. If they are going to approve something early as an emergency use authorization, even if they are going to give an emergency approval for a small group of people early on this year, they still want to see a median safety follow-up time of two months, which is super, super long, but at least that is something as far as if you have sixty days of data on most people to see for side effects, and safety, and tolerability, that gives the FDA some level of confidence in saying, okay, the risk-benefit calculation here, we feel confident enough to issue an emergency use authorization. Even something that basic has become controversial with President Trump saying this is a political decision or this sounds political and that this might slow down getting access to vaccines down the line. It is really two compelling balances as far as the urgency to get something to people as soon as possible, but you also want to make sure it is safe, and you want to make sure it is effective.

Jeffrey: A couple of things that make this political is a few folds. The names that you mentioned they are in the news every single day. Our government made a huge bet, huge bet, financial bet, on these companies and backing these companies. It is in the country’s best interest, obviously, for all of these products to work out, and that was through something called Operation Warp Speed. From a very high level, can you just talk about it and why these vaccines, in particular, are so important to it and how does Warp Speed affect them both from financially and operationally to the market?

Andrew: Operation Warp Speed, that is the U.S. government’s coronavirus vaccine initiative which is basically this very broad sweeping public-private partnership that is pulling together people from HHS, the Defense Department, the few people from the CDC alongside the drug industries, the largest drug makers, and other stakeholders, sort of bringing them all together with the goal of as fast as possible getting a safe and effective vaccine out to Americans. There are also no mRNA vaccines on the market so some people raised concerns as far as this is an unproven platform and it is a pretty big bet to go with Moderna and Pfizer both on that. AstraZeneca, Novavax, Sanofi, Johnson & Johnson, those are all more proven platforms of either protein-based or vector-based vaccines that have generally been approved before as far as how you go from start to finish. Overall, you have these six vaccines under Warp Speed. To accelerate the process, one is doing multiple clinical trials simultaneously. Instead of sequentially doing phase one, waiting for that study to finish, reviewing the data, deciding if we should go to phase two, repeating that process in an orderly fashion, basically, these studies are running simultaneously. The phase one study with Moderna is still technically running. They are still following those patients that were dosed starting in March, getting that long-term safety follow-up, all of that is still going on. But at the same time Moderna started a phase two trial, they started a phase three trial, all of these are running simultaneously. The same thing is going on for Pfizer. The same thing going on for AstraZeneca. Johnson & Johnson just started a phase three trial remarkably quick with basically starting the phase one study in late July, September starting a sixty thousand-person phase three trial. I mean, Warp Speed is the accurate name for it as far as how fast that is going compared to typical vaccine development. One thing to bring up that I have asked about is the idea of you do have a diversity of different technologies that these are using but I think it is also worth noting that they are all going after the same protein of the coronavirus. It is called the spike protein. It is the spiky points, the stick out when you see the graphic, or the cartoon of the virus. From the signs that I have talked to you, they are very confident in it. They think that that is what a vaccine should target. If you have antibodies that neutralize and bind to that spike protein it will be really hard for that virus to get into people and cause disease at the end of the day. Operation Warp Speed is essential to all the work that is going on in the U.S., and sort of trying to coalesce it into an accelerated process and also get manufactured going at the same time. If one of these vaccines does show it works and is effective, there should be at least a few million doses scaling up very rapidly into tens of millions, hundreds of millions of doses throughout the course of the rest of this year and into 2021.

Jeffrey: That is great. Very interesting about the spike protein, I have not heard that before, but it makes sense. I guess with Operation Warp Speed, it is a twelve billion-dollar investment, that is a lot of money but I think it is going to the right places. It is a rush or it is a warp speed to approval, and I do not want to say rush, because that makes it sound like there is no scientific method here, and there is a scientific method. Something you pointed out also that is not looked at, I think, is the fact that Moderna, they did go into phase one, many many months ago and they are still following those people. I think that is helpful, but granted it is only probably twenty or thirty people as opposed to the thirty thousand that we are hoping for. Let us say the end of October or beginning in November, phase three data comes in, what does approval mean? We now have a vaccine that a few people have deemed great in the clinical trial, what does it mean to be approved? Is it FDA approved officially or they are going to say, we saw enough data that we are going to allow you to use it through an emergency use authorization, what is the difference?

Andrew: It is widely expected that any regulatory decisions around a vaccine in 2020 are going to be under the emergency use authorization. We ensure people call that emergency approval. You can contrast that with full approval which is going through a biologics license application. When you hear BLA, so think EUA or BLA, and EUA is most likely going to come first. That is what everyone seems to expect. It would be a stunning surprise if it was just a full approval right off the bat. Basically, with an EUA, it is a lower regulatory bar to allow the FDA to authorize something for use in the public. EUA also lets the FDA craft an approval or tailor an approval test to start in a subpopulation. A lot of the things with my talk to vaccine experts are it is very realistic to expect. If you have Pfizer or Moderna, one of these leading companies, if they have a positive readout that shows, hey our vaccine is effective, here are our two-month safety follow-up data on most of the people. That is a decent chunk of clinical results all around, as far as you get a good amount of short-term safety follow-up, you have that initial effectiveness result. Now, you still do not know what you do not know. You do not know the durability protection, you do not know if this vaccine is going to last three months, six months, a year, or longer. You do not know any long-term safety events and some of the rare serious adverse events. Even with the history of vaccines, you only figure those out honestly, when they are rolled out to the general public, overall. It is a one-in-a-million safety event. Even a thirty thousand person trial will have trouble picking that up just given the rarity of it. But accepting that uncertainty there will be most likely a EUA discussion whenever these results come out if they are positive. That will probably be limited, thinking of groups that are especially vulnerable, where the risk-benefit calculation of getting a vaccine might be more weighed to them, you think of the elderly or people with comorbidities, frontline workers or healthcare workers who are in hospitals with just above-average exposure to the virus. Those people might be tailored to that group specifically. In the EUA, that is going to be the conversation to debate around 2020. If any of this data does come this year and a BLA would come further down the line, I think it is still being worked out what to look for, but a reasonable estimate would be thinking six months of safety follow-up data on tens of thousands of people in the study, to have a real good sense of confidence before you roll it out to hundreds of millions of people that this is surely safe over a fairly long period of time.

Jeffrey: Let us say we do get Pfizer at the end of the month, Moderna a month later, J&J in December, do you think the FDA would wait on an emergency use authorization until all three or four of the first ones the data comes in or do you think it is first one in first one out type of thing?

Andrew: The FDA has committed to having an independent group of scientific experts called an advisory committee, meet, consider each individual coronavirus vaccine when the data supports that type of meeting. I would expect once the data is available for those meetings to be scheduled very quickly after. It is another thing where it is hard to say exactly how quickly this process will work because if you think of a normal application process, it normally takes six or ten months after a company has submitted their data package. The FDA will take six or ten months to look it over, review it, discuss it internally, and make a regulatory decision. It seems inconceivable that they would have that much time just given the urgency here.

Jeffrey: Right.

Andrew: But they have committed to having that independent expert group. I would expect each vaccine to get their own, once that data is ready, I would expect an advisory committee meeting to be scheduled promptly thereafter. There would not be a gating factor as far as wait for the first three. If that first vaccine, if there are enough merits in that data alone to approve it, I think the FDA would make that decision.

Jeffrey: Okay. Pfizer is at the end of the month, immediate meeting and they could be off to the races. Let us combine that thought with the topic of Warp Speed and layer on top of that the question of getting everyone vaccinated, and how all is that going to work. I have a number of questions for you to walk through. Whether it is Pfizer alone, or Pfizer and Moderna, is the government going to grab millions of doses of those first couples of vaccines and just start inoculating as many people as they can whether it just be all the elderly or all the frontline workers. If we find out that, let us say, the J&J or Janssen vaccine in December, has much better clinical trial data than Pfizer that was approved several months earlier, do you think they would stop giving out the Pfizer one and move to J&J? How do you think this is going to work?

Andrew: It is a great question. I have been asking people a lot smarter than me that question for the last few weeks. I think it is just going to be fascinating. I do not know for sure how it is going to work out. I do not think anyone knows a hundred percent how this will all play out. I can say that one thing that we know for sure is these Warp Speed contracts, they basically pre-purchased vaccine supply for all six of these. So for Moderna, Pfizer, whatever company, if it does work, the U.S. government has agreements where they have already bought. For most of these, talking a hundred million doses, most have options where the U.S. government could extend that to buy several hundred million additional doses of those vaccines. So, there is a supply already set up, there are agreements with these companies to get some doses basically immediately once the data supports an approval if it does. What that means as far as if one is superior to the other vaccine, that is a really interesting question that I do not know. There is a lot of ethical considerations in that as far as if you are sitting on, imagine if you have vaccine A and vaccine B, you have data on both, you have pre-purchased supply agreements for a hundred million doses of both that have already starting to be made, and vaccine B look superior, who in the right mind would want to get vaccine A. At the same time, it is an extremely supply constraint where the option for these people might be vaccine A or no vaccine at all. It is really complicated. I do not have a clear answer. I have asked Moncef Slaoui, the head of Operation of Warp Speed, a very similar question maybe forty-five days ago or so when I last spoke with him and he basically sorts of punted on it and just said hopefully, the clinical data, subpopulations, will be enough distinctions where that will work itself out. I mean what you want to see here and this is sort of playing out in real-time is the FDA set clear guidelines on what they want for this data before we see the data. I think that is the fairest way of doing it and that is what I have been talking with experts about is what would you actually like to see in the data? What does a good vaccine look like? What does an adequate vaccine look like? What does an excellent vaccine look like? As fas as getting the idea of six thousand people who have received two doses and been followed for at least two months. If that is the safety database, what does that tell us? What would not that tell us about the vaccine? The American public has to feel confident in the regulatory process and the fact that these decisions are made by science instead of politics. If they are going to even consider getting a newly approved vaccine and it has been remarkable to see some of the tension play out in public between the FDA and the White House. That has really surprised me. The FDA several months ago, this was a really good job by them, as far as when you look at hindsight, they put out guidance around that full BLA. So thinking about that full approval and they basically said, we are not going to approve any vaccine that is less than fifty percent effective, and they outline the safety data they would want. That has sort of established this idea of, okay, to get that, these companies are going to run studies with thirty thousand people and then you see that number reflected in the studies and so on and that has worked well as far as those goalposts were established. They are very clear, they are publicly available, it is transparent. The emergency use authorization that is what is being caught up in this controversy within the government to some extent, especially around this two-month safety follow-up data. We are talking goalposts there, those have not been publicly stated formally yet by the FDA for EUA. So, that is something to watch these next few weeks, if they are able to do that or if we are just going to roll into data, it will be a little more free-flowing to sort of think about it as far as — You could imagine if something comes out that is fifty-five percent effective, it cleared the bar for BLA approval, and get FDA approval, but that would still leave a lot of room for improvement for future vaccines to be more effective.

Jeffrey: Right, and getting people excited about taking that vaccine that is only fifty-five percent effective. It is going to be tough as well.

Andrew: Right. I think the other point that is still not really as evidence to the public as it probably needs to be, in terms of expectation setting, is the idea that even when you get a vaccine, especially it is most likely going to be partially effective to some effect, it is not going to be getting a vaccine and you cannot go throw away your mask the next day and start going to bars, and stop social distancing, and whatnot. Getting out of the pandemic, it is a kind of a vaccine is an incredibly valuable tool and the toolkit here against the pandemic. It is seen by experts as yes, you get the vaccine, and you wear a mask, and you socially distance. When enough people do multiple of these measures that is how the pandemic ends much more quickly.

Jeffrey: Right.

Andrew: It is kind of a bummer to here as far as you here all the time. Until we get a vaccine XYZ, when there is a vaccine, even when there is a vaccine, there is a good chance we are still wearing masks and socially distancing as that distribution goes out. You need hundreds and millions of people to really have a sense of community protection.

Jeffrey: Andrew, thank you so much. This has been, as usual, your insight knowledge of this area is fantastic and we very much appreciate you sharing that with us.

Andrew: Thanks so much for having me on, Jeff. I really appreciate it and I love the podcast. Keep doing it.

Jeffrey: We hope you enjoyed this week’s podcast. If you have any questions, comments, or future story suggestions, please reach out to us on social media. Thank you, and we hope you enjoyed the RP HealthCast.

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