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Vaccine economics: how Covid-19 will disrupt the vaccine market

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Of all the products in the world you don’t want to use market-based prioritisation, it’s got to be vaccines.

There’s no technology known to man now that is faster than mRNA.

Because of this monopoly or duopoly position that the sellers are in, they tend to have a high amount of market power and ability to get higher prices.

Vaccines save two to three million lives every year. But bringing them to market involves huge investment, complex science, and secretive contracts. Before the Covid-19 pandemic few people paid attention to the business models behind vaccines. The global pharmaceutical market was worth $1.3tn in 2019. Vaccines made up just 3 per cent of that, generating around $33bn of revenue, that compared to $142bn from cancer drugs.

So how do the economics of vaccines work? Who funds them? How profitable are they? And will the Covid-19 pandemic and new technology disrupt the vaccine market forever?

Until recently, there have really only been four main players in the vaccine market, GlaxoSmithKline, Merck, Pfizer, and Sanofi. They represented 90 per cent of vaccine industry revenues in 2019. Even for these market leaders developing a vaccine is a costly and time-consuming gamble. The process often takes a decade.

Work on infectious diseases is often very obscure because the burden is so much out of sight in the rich countries and where the deep scientific and manufacturing power is.

Government is the main funder of the science. And that’s critical. And all of the benefits we have today, if you think about the sequence analysis or the mRNAs and the biotechnology, the new manufacturing, all of that came out of investments in basic science.

As you go into phase 1 trials these are taken over by industry. Maybe 1 in every 10 vaccines in a phase 1 trial goes on to be approved while 50 per cent to 70 per cent of vaccines in phase 3 trials end up being approved.

They will only invest once the market and the chances of success are well-known. This doesn’t mean there’s zero risk. But largely what we see is that the public sector takes on most of that. Indeed, this is what allows the business of vaccines to operate.

The cost of creating a vaccine varies widely. On average it ranges from several hundred million to a few billion dollars. Supply, demand, and pricing for vaccines are determined by a small number of actors.

On the buyers side, national governments and organisations like Gavi, the Vaccine Alliance, and Unicef are among the biggest purchasers. On the sellers side are the pharma companies. Because the development costs and regulatory barriers for vaccines are high, companies can maintain their monopolies for longer.

They tend to have a high amount of market power and ability to get higher prices than, let’s say, a generic small molecule drug or even a vaccine for which we have lots of competitors.

Up until Gavi was created, the global alliance for vaccines, in the year 2000, there was no purchasing power to get those new vaccines to the kids who needed them most. So that was this great irony that, for example, rotavirus and pneumococcus vaccines that now save millions of young children’s lives, they weren’t getting out in these countries.

Normally, what happens is when vaccines come out, they come out at a high price and a low volume. And over time, as the yield goes up, as other manufacturers begin to produce it, prices come down dramatically. To give an example, our vaccines that are the WHO-approved vaccines cost over $1,300, if you looked at it in the US model, and we pay $27 for those. So it’s a pretty dramatic difference.

Gavi typically negotiates procurement on behalf of 60 per cent of the world’s children. They try to ensure low and middle income countries pay significantly less for vaccines than rich countries do.

If the disease is in the rich world, one of the western companies will invent a new vaccine with huge R&D investments They’ll charge a reasonably high price, as much as, say, $100 in western markets. And then eventually, either they’ll make a cogs-oriented version or the Indian or other developing country manufacturers will come in.

By prioritising high volumes at low prices, the Serum Institute of India has become the world’s largest vaccine manufacturer by volume. It typically produces more than 1.5bn doses of vaccines every year, which are used in 170 countries. This year, it has increased capacity and is aiming to manufacture at least 1bn doses of Covid-19 vaccines alone, after signing deals with AstraZeneca and Novavax.

It is more expensive to make a vaccine in the US and Europe. Traditionally, those companies haven’t had large facilities because the volumes that they sell at are much lower, but at a very high price.

Well, these are proprietary products that the companies have spent lots of money and high risk in order to go through trials. They have to recover all of those and make their profit from the rich world market and the middle income market, knowing that those Gavi markets are not going to give them any meaningful margin.

But returns on investment are not straightforward. The lack of transparency around each company’s production costs makes it difficult to assess a vaccine’s profitability. We do know that at the top end, Pfizer’s pneumococcal vaccine Prevnar, which works against pneumonia, generated $5.8bn in revenue in 2019.

If you’ve invested maybe a few hundred million dollars in the R&D 10, 15, 20 years ago and you have a captive market, then you’re going to make a pretty good profit, a very, very healthy profit, some might even say an excessive profit.

At the other end of the spectrum are well-established, low-cost children’s vaccines like measles. Low profits drove several producers out of the market in the 1970s and ’80s. In the past decade an increase in vaccines for adults and those taken annually like the flu vaccine have helped make the market more profitable. But for governments, the health, societal, and economic returns are much greater. Gavi estimates a $21 return for every dollar invested in vaccine programmes for the 73 countries it typically supports.

Well, the most salient number is that in the year 2000 over 10m children under the age of five died every year. By 2016, that number was under 5m per year. That’s per year. That’s millions.

This is the way things were. Then came the pandemic. The outbreak of Covid-19 brought China and then Europe to a standstill. As the novel coronavirus spread to the US and across the globe, it wasn’t long before governments were betting billions of dollars on developing vaccines to fight the pandemic. A new vaccine market was about to emerge, where demand was unlimited and governments would do everything in their power to secure doses.

The total amounts involved relative to normal vaccine R&D, it’s tens of billions of dollars, maybe a total of $25bn or so. That’s gigantic in the world of vaccines. Now, relative to the economic damage of the pandemic, which is in the trillions, it’s truly a rounding error. This is the best money that’s been spent by governments during this pandemic.

The public sector, governments collectively, have really de-risked and subsidised the R&D process every step of the way, from the earliest stages of R&D oftentimes to the scale-up of manufacturing and of course purchasing.

Other big funders include the Bill and Melinda Gates Foundation and CEPI. The Coalition for Epidemic Preparedness Innovations is a public-private partnership that supports vaccine development to stop future epidemics. One recipient of a small grant from CEPI at the start of the pandemic was Moderna, a biotech company that had yet to bring a product to market. By the end of 2020, US federal funding for Moderna’s vaccine had swelled into the billions, and it was approved for use.

So Moderna took a huge amount of public money, up to $4bn from the US government. And that helped them build this proof of concept. The vaccine uses messenger RNA technology which the company spent a decade developing.

We invested around $3bn in the last 10 years to get the technology to this place. The pandemic has accelerated the company’s turning into a commercial company by three to maybe four years.

The first vaccine approved in a western country also used mRNA. It was made by US pharmaceutical giant Pfizer and Germany’s BioNTech. While Pfizer did not take public funding to develop and manufacture its vaccine, it did have an initial $1.95bn advance purchase agreement through Operation Warp Speed. The US government’s Covid-19 investment programme has surpassed $10bn, most of which has been spent on vaccines.

It’s not the only country that placed huge bets on vaccines. China and Russia funded their own vaccine candidates. And the German government gave BioNTech $445m. The UK government contributed £65.5m to Oxford university. And its vaccine manufacturing partner AstraZeneca received up to $1.2bn for trials and manufacturing from the US government.

Well, there was no point in us generating a vaccine in January of last year if it wasn’t going to be able to be taken all the way through clinical development and into emergency use licensure. And as a university we are able to do much of the early clinical development and get that taken quite a long way, but we were never going to be able to manufacture a vaccine that was going to be used as a licenced product.

The unprecedented public funding helped these companies develop vaccines in less than a year. Until now, the fastest vaccine ever created was a mumps vaccine developed by Merck in four years. The pandemic demanded an urgent response. But that also led to questions about the prices of Covid-19 vaccines.

We have a high degree of secrecy. We have governments really desperate for access to vaccine supplies and willing to sometimes pay very, very high prices. And things are happening very quickly under emergency conditions. So it’s, unfortunately, a perfect storm, where the risk of abusive pricing or unfair pricing is quite high.

I think pharma did hold a lot of power in this negotiation, but I also think that they could have gone higher. Plenty of investors actually would have liked them to have gone higher and didn’t make a secret of that.

Prices for Covid-19 vaccines vary widely. The Oxford/AstraZeneca vaccine is about $3 to $4 a dose. Along with Johnson & Johnson, they have committed to selling their vaccine on a non-profit basis during the pandemic. AstraZeneca say they will do so in perpetuity for low and middle income countries. Moderna said it has charged the US government as little as $16.50 per dose to return some money to taxpayers, but smaller orders for other customers range from $32 to $37 per dose.

We invested $3bn in this technology since the beginning. We’ve never made a penny of profit. We thought it was not appropriate not to make a small profit. The value that we are asking for the product is way under the value to the healthcare system. If you just look at the saving in just hospitalisation costs, they’re running much, much higher per inhabitant.

It’s very difficult to actually come up with an evidence-based judgement on the fairness of any price or the fairness of any profit margin.

Companies want to play countries off against each other and so aren’t very incentivised to want to make these contracts transparent. And democratic governments often don’t want their public to know that they’ve gotten a bad deal or they don’t want rival countries to know that they’ve gotten a good deal. And so there’s not very much incentive for making these public.

Before the pandemic, US pharma companies were under pressure over high prices for drugs. The industry looked ripe for reform.

So then we come into the pandemic and you have a situation where some companies say, look, this shows how important it is to invest in innovation, so you should pay us a good amount of money. But then on the other hand some companies said, ah, this is our opportunity to make a contribution by saying, we’ll offer these vaccines on a non-for-profit basis.

I think it’s reasonable to allow companies to make a profit from the high income countries, having put such a huge effort into this work, and also make sure that it will be available for low and middle income countries in perpetuity without profit.

Moderna said it expects to make $18.4bn from its Covid-19 vaccine sales this year. It has not revealed the profit margin for its Covid-19 vaccine. Pfizer said it expects to make about $15bn with a profit margin of more than 20 per cent. The profits will be split 50/50 with BioNTech. These forecasts have partly shaped the companies’ varied share price performances in the past year.

In previous pandemics, including Sars, the outbreak ended before companies could develop a vaccine. Those who invested in the endeavour made a loss. But Covid-19 is widely expected to become endemic. Analysts predict the annual vaccine market for the virus could reach $10bn a year or more, as producers tailor vaccines for new strains.

If the vaccines aren’t very successful but they do provide a very meaningful contribution to the fight against Covid then we’re likely to move to something like a flu model, where we sell more vaccines for the flu than we do for every other vaccinated illness in the world.

Then the question will be, are there so many competitors in the market that the price falls? Or the price may go up because it will be more of a natural, normal market, where people will perhaps choose a particular vaccine because it has a higher efficacy rate rather than a market where it’s controlled by these gigantic government contracts.

One big question is whether governments should have demanded more in these deals for subsidising development and guaranteeing sales.

It does feed into a larger debate that was already happening about what happens when governments fund science, especially really basic research. It goes on into the private sector and it makes the private sector a lot of money, but not much of that flows back to the government.

For governments of low and middle income countries, the return on investment calculation is entirely different. They are battling just to secure supplies of Covid-19 vaccines amid a flurry of bilateral deals between rich countries and vaccine producers and global disputes about controls over vaccine supply chains.

Of all the products in the world you don’t want to use market-based prioritisation, it’s got to be vaccines. Because if you went that way the rich people and the rich countries would buy all the output for quite a while and it wouldn’t be assigned according to who’s at risk of dying, for example, getting to the elderly and the healthcare workers.

Gavi, the World Health Organization, and CEPI set up the COVAX programme to mitigate this and provide equitable distribution for Covid-19 vaccines. The COVAX Advance Market Commitment, or AMC, has raised $6.3bn and aims to distribute 2bn doses this year with two-thirds of those subsidised for 92 lower income countries.

We also hoped that by having global supply it would reduce the number of bilaterals. And it looked like that might have helped for a while. But there really has been a global panic, given seeing doses being rolled out, people hoarding doses. And also, the new variants have made people nervous.

There are some governments that have said, yes, we politically support COVAX, we will put money into COVAX, it will subsidise other countries through COVAX, they are the very same governments that have turned around and said, we are going to basically eat up most of the world’s existing volume through advance purchase commitments.

Any head of state is going to think about, I have to protect my people. That’s a natural instinct. And that may be true in a normal situation. But in a global pandemic, you’re only as safe as everyone is safe.

Covid-19 has turbocharged normal market forces, from funding to the speed at which vaccines were developed and the subsequent international scramble to buy them. But are there more fundamental ways the virus will change the vaccine market?

I think the Covid-19 pandemic will completely shake up the vaccine market. And that’s because of these new technologies like messenger RNA and viral vectors. By accelerating them so fast, they’ve completely shaken up who’s on top, who has the potential to create the next vaccine.

The fastest vaccine ever [created] had been four years. The Ebola vaccine was around five years. And the fact that this happened in 303 days is extraordinary.

The pandemic was an opportunity to prove that mRNA, or messenger ribonucleic acid, technology could work. The synthetic mRNA delivers instructions to cells in the body to produce the viral protein, which stimulates an immune response. The success of Pfizer/BioNTech and Moderna’s mRNA vaccines mean the technology could be applied to a wide range of other vaccines and drugs.

The mRNA platform, we’re going to push that to the limit. And we should get a lot more vaccines. And a malaria vaccine or an HIV vaccine or a TB vaccine are miraculous things. That’s measured in saving millions of lives, not some economic thing. That is about life itself.

The speed at which mRNA vaccines can be tweaked to respond to new variants and then mass produced could also make vaccines more profitable.

We’re going to end up having technologies like mRNA enabling new vaccines that are going to be best in class and first in class, that are going to be able to maintain a high profitability.

I think platform technologies are the future of vaccine development, and messenger RNA is one of them. We haven’t really seen messenger RNA vaccines widely used at all before 2020. And in the last year they’ve gone from being something of a niche research area into having massive impact.

I believe we will end up, at Moderna, having the vaccine that will have a combination of a seasonal boost for flu and the new variant for SARS-CoV-2 and it’s going to be one shot. So how is that going to compete with a vaccine that only does seasonal flu? I believe those vaccines will have no future.

There are also reasons to be cautious about the future of mRNA.

Just because mRNA and the viral vector vaccines have been pretty successful for Covid doesn’t mean they’re going to be successful for everything else. And so I think that there will still be a debate inside some of these big vaccine players like GSK, Sanofi, and Merck about to what extent they should rush towards this new, shiny object and to what extent they should rely on their own reliable proprietary platforms.

I do think for the next pandemic we will be able to solve the problems of the mRNA platform. That is, we’ll fix the thermal stability, we’ll fix the scalability, and we’ll fix the cost. We caught mRNA halfway to prime time.

Analysts predict that 2021 vaccine sales from Moderna and Novavax will outpace those from three of the biggest vaccine producers who dominated the market before Covid-19 — Merck, GSK and Sanofi. All three have yet to bring a Covid-19 vaccine to market.

There are new players in charge. They’ve got a lot of capital. Investors are really backing them. And they can go into new markets, most obviously flu.

The big question, the billion dollar question, is, how many of those firms are going to find a business model that allows them to scale up production and global distribution?

Could the pandemic propel the vaccine segment into becoming a much bigger part of the global pharmaceutical market?

Vaccines probably save more lives than any other tool. If we can take vaccines and apply them more in the area of cancer, then that just changes the numbers completely. Because the cancer market is… it’s over 10 times the R&D, over 10 times the spend, potential for growth.

I do not think that we’re going to see the entire pharma industry switch to focusing on vaccines. It’s still a business where you often sell to governments, where there are often very large contracts and not that much competition and not that much growth.

With more than 113m cases of coronavirus confirmed globally and 2.5m known deaths, vaccines are widely seen as the key to ending the pandemic. Public investment in vaccines are dwarfed by the economic costs of this global health crisis. An estimated $6tn in economic output was lost in 2020 and another $4.4tn will be lost this year.

Public health experts have been telling governments and politicians for years that vaccine supply is a huge global strategic priority and that you should protect it. I think they’ve finally woken up.

Traditionally, when governments have tried to invest in that infrastructure it’s not worked out very well. It’s always been the private players and the private sector that’s been able to succeed, scale up, because of the entrepreneurship and freedom that a private sector company would have.

Obviously, if you want to have manufacturing facilities ready to go that are there in case of an outbreak, you’re going to need to make sure that there’s financing for that. Because from a for-profit company, the idea that you would have facilities that are available that are not being optimally used might not make business sense, but they may make public health sense. So I see this as a partnership between government and the private sector.

I’m very enthused that vaccines… all the standby capacity that we will have on it for the next pandemic, we may be able to use that when there’s not a pandemic going on to create lots of low-cost supply capacity for the entire world. Imagine that you’d had a vaccine back in the summer. You would have saved millions of lives.

Covid-19 has already changed the vaccine market, potentially irreversibly.

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