Hey, John: can you comment on the AstraZeneca/Gameleya cooperation agreement announced recently? As a virologist who works for Big Pharma, you might have insights, I figure.
One question that occurs to me: why bother? By the time they can validate a combined protocol of their two vaccines, won't there be 8 or so vaccines already approved and on the market? I figure two or three from China, J&J, Novavax, and at least three others.
Good question, but I do have to clear up that I don't really work in "Big Pharma." I work at a relatively small scale independent biopharma company. In the past I've been a supporting scientific services vendor for Big Pharma companies like Novartis and Pfizer, though.
I think this type of collaborative agreement is extremely common in the business. If you have a treatment that works well and someone else has a component that works well also, then it's not a difficult argument to make that you should try to see if they work better together. I expect to see a lot of these types of agreements made between various entities that are developing vaccines.
In the case of Gamaleya and the AZ/Oxford vaccine, the combination makes even more sense because it's clear that immune reactions to the scaffold virus used to build these chimeric vaccines interfere with the quality of the immune reaction to the presented SARS-CoV-2 antigens. By combining them, they might have a way to create double the SARS-CoV-2 signal with half the off-target signals, and hopefully improve both vaccines. Remember that AstraZeneca's vaccine worked best when patients were primed with a half-strength dose. Perhaps by working in combination with the Sputnik V vaccine, they can get an even better result built off that finding.
"Why bother" is a good question. Let's keep in mind that we don't really know for sure what the duration of immunity induced by these vaccines will turn out to be. COVID-19 is very likely here to stay, and if reinforced immunity is required every couple of years, a vaccine is going to be an in-demand product. What's more, it's possible that any of these candidates will induce longer-lasting immunity than the others. The ballgame isn't finished.
That said, it's important that these companies finish their trials soon. As the first-to-market vaccines get introduced to new populations, it will become ever more difficult to find patient groups that can still be ethically enrolled in placebo-controlled trials. Instead, whoever is latest to the party is going to have to conduct "noninferiority" trials in comparison with active vaccination. That will be a harder bar to pass. So the faster these companies get their agreements in place, the better, so they can get their trials finished. Also, there's the benefit that this gets vaccines to market for all of us to use a lot faster than if they could afford to wait.
That said, I think everyone is underestimating the way that the entire vaccination industry will change as a result of COVID-19. I'll note here that I have a long-term stock position in Moderna as well as Pfizer, which I initiated over the summer, partly because of the advance that these vaccines represent beyond just COVID-19. mRNA vaccines have the potential to completely change how vaccination works, especially routine vaccinations that are currently conducted using protein subunit vaccines. mRNA vaccines can be made quickly and cheaply and redesigned with ease. A lot of vaccines that are on the market right now could work much better in this format. I think that Pfizer and Moderna's unexpected magnitude of success with these two vaccines makes it very hard to predict "what happens next" based on the traditional assumptions that are made in the industry regarding vaccine development. I'm not sure I really can predict what comes next after this.
One thing I think we can bet on is that not all the vaccine candidates are going to do as well as the Pfizer and Moderna candidates have so far. As other candidates mature to results, we'll see how much need remains for additional vaccines and regimens. Clearly AstraZeneca and Gamaleya think that there will be quite a lot of need.
You aren't the first to say that mRNA vaccines can be made inexpensively ... but the Pfizer and Moderna vaccines are actually an order of magnitude more expensive than others, according to the general press.
I can't find any corroboration of this claim anywhere, I'm afraid. I was speaking about the development costs there, so I'll answer regarding development costs first, but we'll turn to another interpretation of your statement in a moment.
The Pfizer and Moderna vaccines, representing a breakthrough technology being brought to market for the first time, took on research investment and costs around $1-2 billion USD. This is on the expected order of magnitude for the development of a run-of-the-mill vaccine as estimated in these various sources:
Across those estimates, $1 billion USD seems to be the most reasonable number, but I'll note that the high end in the first article is around $5 billion. The Moderna and Pfizer vaccines definitely did not cost an order of magnitude more than this to develop, and what's more is that these were first-in-class vaccines proving an unproven technology. Normally, doing that sort of thing is substantially more expensive than reworking a proven technology. Now that this mRNA technology is proven, it will be substantially less expensive to develop the next RNA vaccine than it was to develop these first ones, in under a year, during a global pandemic.
If you mean that the cost per dose is an order of magnitude higher than for other vaccines, that's not a fair comparison. Most other vaccines have been on the market for a very long time and have been mass produced for years, with a lot of price competition setting in to drive their costs down. Even considering that, though, vaccines can be quite expensive. Moderna is currently offering its vaccine at the highest retail price (governments have negotiated this down, but let's use the high price) of $34 to $37 USD. For comparison's sake, an influenza vaccination typically costs between $30 and $100 in terms of what insurers pay. So that's at least the same order of magnitude in cost if not actually lower by an order of magnitude.
I'm afraid that any way I look at that claim I can't really corroborate it. I don't know where you read it but it doesn't appear to be correct.
I was speaking of cost per dose, yes. AZ's vaccine, $3 for a single shot. Moderna's, $30 per shot, 2 shots needed..
Saying they could potentially be cheaper in the future is not the same as saying they "are" cheaper.
I was being slightly hyperbolic, with the Novavax and J&J vaccines both costing something in between those values, but Moderna's vaccine is certainly not the least expensive. (Pfizer's is second-most expensive.)
Correction, AZ is also making a two-doze vaccine. I knew that. An earlier edit of that post was referring to the one-shot J&J vaccine. Knew it was wrong as soon as I hit "Post".
So, replying to all of this at once, it's clear you're talking about cost-per-dose. This definitely wasn't what I was talking about. However, all that being said, the competitive pricing that you're citing is artificial. AZ and J&J are both offering their vaccines at strict manufacturing cost, no profit, in what is essentially a goodwill PR move. They are not pricing in development costs (which incidentally were mostly paid for with public funds anyhow) and they are only doing this until an end is declared to the pandemic. This does not reflect the actual retail price of a course of their vaccine and doesn't at all compare to what vaccines typically cost. When you said "other vaccines" it wasn't clear that you meant "other COVID vaccines," but let's keep in mind that all the pricing for all of these vaccines is exceedingly distorted due to the funding sources, bulk buys, and a desire by large pharma companies to show how nice and friendly they are by offering the vaccine on the cheap.
Moderna, meanwhile, is a startup that has never been revenue-positive until this vaccine. They're charging a realistic price because they don't have money to burn.
I think it's a lot more appropriate to compare the mRNA vaccines to vaccines for other diseases for this reason, and by that comparison they are either similarly-costed or somewhat less expensive. Compared to the pneumococcal pneumonia vaccine Prevnar 13, which costs around $170, these are a bargain.
Either way, both in terms of development costs and in terms of cost per course, the Pfizer and Moderna vaccines are substantially less expensive than many vaccines have been in the past. And that's just for the first development cycle. mRNA vaccines are definitively cheaper to develop and cheaper to produce, and I'm not saying that as a forward-looking statement. It can cost up to $5 billion to develop a new biologic treatment, the class into which vaccines fall. Both of these mRNA vaccines were made for a lot less than that.
Development costs are the dominant outlay in pharmaceutical manufacturing, so this is a big deal. Production for almost any vaccine is a few dollars per dose, though I do expect RNA vaccines to be marginally cheaper given that you don't need finicky bioreactors like you do with protein synthesis.
So, speaking of development costs, yes, they're cheaper, already.
Hey, John: can you comment on the AstraZeneca/Gameleya cooperation agreement announced recently? As a virologist who works for Big Pharma, you might have insights, I figure.
One question that occurs to me: why bother? By the time they can validate a combined protocol of their two vaccines, won't there be 8 or so vaccines already approved and on the market? I figure two or three from China, J&J, Novavax, and at least three others.
Good question, but I do have to clear up that I don't really work in "Big Pharma." I work at a relatively small scale independent biopharma company. In the past I've been a supporting scientific services vendor for Big Pharma companies like Novartis and Pfizer, though.
I think this type of collaborative agreement is extremely common in the business. If you have a treatment that works well and someone else has a component that works well also, then it's not a difficult argument to make that you should try to see if they work better together. I expect to see a lot of these types of agreements made between various entities that are developing vaccines.
In the case of Gamaleya and the AZ/Oxford vaccine, the combination makes even more sense because it's clear that immune reactions to the scaffold virus used to build these chimeric vaccines interfere with the quality of the immune reaction to the presented SARS-CoV-2 antigens. By combining them, they might have a way to create double the SARS-CoV-2 signal with half the off-target signals, and hopefully improve both vaccines. Remember that AstraZeneca's vaccine worked best when patients were primed with a half-strength dose. Perhaps by working in combination with the Sputnik V vaccine, they can get an even better result built off that finding.
"Why bother" is a good question. Let's keep in mind that we don't really know for sure what the duration of immunity induced by these vaccines will turn out to be. COVID-19 is very likely here to stay, and if reinforced immunity is required every couple of years, a vaccine is going to be an in-demand product. What's more, it's possible that any of these candidates will induce longer-lasting immunity than the others. The ballgame isn't finished.
That said, it's important that these companies finish their trials soon. As the first-to-market vaccines get introduced to new populations, it will become ever more difficult to find patient groups that can still be ethically enrolled in placebo-controlled trials. Instead, whoever is latest to the party is going to have to conduct "noninferiority" trials in comparison with active vaccination. That will be a harder bar to pass. So the faster these companies get their agreements in place, the better, so they can get their trials finished. Also, there's the benefit that this gets vaccines to market for all of us to use a lot faster than if they could afford to wait.
That said, I think everyone is underestimating the way that the entire vaccination industry will change as a result of COVID-19. I'll note here that I have a long-term stock position in Moderna as well as Pfizer, which I initiated over the summer, partly because of the advance that these vaccines represent beyond just COVID-19. mRNA vaccines have the potential to completely change how vaccination works, especially routine vaccinations that are currently conducted using protein subunit vaccines. mRNA vaccines can be made quickly and cheaply and redesigned with ease. A lot of vaccines that are on the market right now could work much better in this format. I think that Pfizer and Moderna's unexpected magnitude of success with these two vaccines makes it very hard to predict "what happens next" based on the traditional assumptions that are made in the industry regarding vaccine development. I'm not sure I really can predict what comes next after this.
One thing I think we can bet on is that not all the vaccine candidates are going to do as well as the Pfizer and Moderna candidates have so far. As other candidates mature to results, we'll see how much need remains for additional vaccines and regimens. Clearly AstraZeneca and Gamaleya think that there will be quite a lot of need.
You aren't the first to say that mRNA vaccines can be made inexpensively ... but the Pfizer and Moderna vaccines are actually an order of magnitude more expensive than others, according to the general press.
I can't find any corroboration of this claim anywhere, I'm afraid. I was speaking about the development costs there, so I'll answer regarding development costs first, but we'll turn to another interpretation of your statement in a moment.
The Pfizer and Moderna vaccines, representing a breakthrough technology being brought to market for the first time, took on research investment and costs around $1-2 billion USD. This is on the expected order of magnitude for the development of a run-of-the-mill vaccine as estimated in these various sources:
https://www.passporthealthusa.com/2018/02/how-much-does-it-cost-to-develop-a-new-vaccine/
https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(18)30346-2/fulltext
https://www.washingtonpost.com/news/wonk/wp/2014/11/18/does-it-really-cost-2-6-billion-to-develop-a-new-drug/
Across those estimates, $1 billion USD seems to be the most reasonable number, but I'll note that the high end in the first article is around $5 billion. The Moderna and Pfizer vaccines definitely did not cost an order of magnitude more than this to develop, and what's more is that these were first-in-class vaccines proving an unproven technology. Normally, doing that sort of thing is substantially more expensive than reworking a proven technology. Now that this mRNA technology is proven, it will be substantially less expensive to develop the next RNA vaccine than it was to develop these first ones, in under a year, during a global pandemic.
If you mean that the cost per dose is an order of magnitude higher than for other vaccines, that's not a fair comparison. Most other vaccines have been on the market for a very long time and have been mass produced for years, with a lot of price competition setting in to drive their costs down. Even considering that, though, vaccines can be quite expensive. Moderna is currently offering its vaccine at the highest retail price (governments have negotiated this down, but let's use the high price) of $34 to $37 USD. For comparison's sake, an influenza vaccination typically costs between $30 and $100 in terms of what insurers pay. So that's at least the same order of magnitude in cost if not actually lower by an order of magnitude.
I'm afraid that any way I look at that claim I can't really corroborate it. I don't know where you read it but it doesn't appear to be correct.
I was speaking of cost per dose, yes. AZ's vaccine, $3 for a single shot. Moderna's, $30 per shot, 2 shots needed..
Saying they could potentially be cheaper in the future is not the same as saying they "are" cheaper.
I was being slightly hyperbolic, with the Novavax and J&J vaccines both costing something in between those values, but Moderna's vaccine is certainly not the least expensive. (Pfizer's is second-most expensive.)
Most convenient source: https://www.healthline.com/health-news/how-much-will-it-cost-to-get-a-covid-19-vaccine#How-much-each-dose-will-cost
Correction, AZ is also making a two-doze vaccine. I knew that. An earlier edit of that post was referring to the one-shot J&J vaccine. Knew it was wrong as soon as I hit "Post".
So, replying to all of this at once, it's clear you're talking about cost-per-dose. This definitely wasn't what I was talking about. However, all that being said, the competitive pricing that you're citing is artificial. AZ and J&J are both offering their vaccines at strict manufacturing cost, no profit, in what is essentially a goodwill PR move. They are not pricing in development costs (which incidentally were mostly paid for with public funds anyhow) and they are only doing this until an end is declared to the pandemic. This does not reflect the actual retail price of a course of their vaccine and doesn't at all compare to what vaccines typically cost. When you said "other vaccines" it wasn't clear that you meant "other COVID vaccines," but let's keep in mind that all the pricing for all of these vaccines is exceedingly distorted due to the funding sources, bulk buys, and a desire by large pharma companies to show how nice and friendly they are by offering the vaccine on the cheap.
Moderna, meanwhile, is a startup that has never been revenue-positive until this vaccine. They're charging a realistic price because they don't have money to burn.
I think it's a lot more appropriate to compare the mRNA vaccines to vaccines for other diseases for this reason, and by that comparison they are either similarly-costed or somewhat less expensive. Compared to the pneumococcal pneumonia vaccine Prevnar 13, which costs around $170, these are a bargain.
Either way, both in terms of development costs and in terms of cost per course, the Pfizer and Moderna vaccines are substantially less expensive than many vaccines have been in the past. And that's just for the first development cycle. mRNA vaccines are definitively cheaper to develop and cheaper to produce, and I'm not saying that as a forward-looking statement. It can cost up to $5 billion to develop a new biologic treatment, the class into which vaccines fall. Both of these mRNA vaccines were made for a lot less than that.
Development costs are the dominant outlay in pharmaceutical manufacturing, so this is a big deal. Production for almost any vaccine is a few dollars per dose, though I do expect RNA vaccines to be marginally cheaper given that you don't need finicky bioreactors like you do with protein synthesis.
So, speaking of development costs, yes, they're cheaper, already.