The first human data of the most advanced COVID-19 vaccines have been disclosed over the past couple of months (see references in our tracker of the European "COVID" biotechs), but the first pre-orders have even been registered without having seen any data. The preliminary immunogenicity and safety data have been sufficiently promising to keep this "first wave" of pre-orders going on. These pre-orders are from various countries across the world, but the most important in quantities -and in value- reasonably come from the Western countries and Japan.
The US Federal Government has deployed important financial means to secure and prioritize the delivery of such vaccines for the US people (almost 10 billion USD to date), notably through the "Operation Warp Speed". This program was launched by the current US administration in the middle of May, and already includes a number of deals with the most advanced Pharma or biotech companies (Table 2 below), with the first deliveries hoped by the end of this year for the most advanced candidates.
In Europe (Table 1 below), a group of four countries -Germany, France, Italy, Netherlands- had started to play solo (June 15th agreement with AstraZeneca), but eventually played the collective card, after the irritation of other EU Member States (agreement finalized on August 14th, expanded to all the EU Member States). We received the clarification from the EC, that the European organization had "received a request of the group of four countries to the Commission to take over the contract and finalise it on behalf of all Member States. There will be no other contract for advance purchase of COVID-19 vaccines between AstraZeneca and EU Member States".
With yesterday's disclosure from Moderna Therapeutics (up to 160 million doses for the EU Members), the European Commission would have already signed initial pre-orders for more than 1.1 billion doses of various COVID vaccines, or more than 1.6 billion doses with options for additional doses. The only financial terms disclosed for a European deal so far are those from the group of four countries mentioned before, with a consideration of 750mEUR or ~843mUSD for 300 million doses (2.5 EUR or approximately 2.8 USD per dose). In the US, the figures disclosed so far let us estimate an implied price per dose of 9 or 10 USD (weighted average), or 18-20 USD for a vaccination course of typically 2 doses, as it is the case for the leading vaccine candidates, as of today. Of note, the estimates take into account external funding for the R&D, the clinical trials, and the manufacturing of these vaccines (particularly for the scale-up), which potentially leads to large overestimates versus the actual billed prices. Bill Gates, who is involved in the development of vaccine with the Bill & Melinda Gates Foundation, mentioned last week, during an interview with The Economist, that the estimated price per dose would likely be in the 2-3$ range for the candidates not using the new mRNA approach (AstraZeneca, J & J, Sanofi / GSK, Novavax). This estimate probably assumes no profit, but is in line with the terms of the AstraZeneca deal inked by the group of four European countries, the British pharma having mentioned to provide the vaccines at "no profit".
You will find below a summary of the COVID vaccine supply agreements for the main territories (number of doses, and if disclosed, some contract or funding amounts), starting with Europe, since we are basically focused on the European biotech landscape. We also included the data for the UK, as well as the data for Switzerland (Table 1). We also provide the data for the US and Japan (Table 2).
As of 25/08/2020, the UK government has secured initial orders for approximately 2.5 courses per British inhabitant (6 agreements), which is by far the most important booking per person in our selected countries/areas. However, nobody really knows today at which level the attrition will be for the current vaccine candidates, as it seems unlikely that all of them will get to the finish line, at least for the tens or hundreds in development.
Indeed, one has to keep in mind that the vaccine candidates still have to prove their safety and efficacy in large-scale randomized clinical trials. The approvals of these vaccines are still to be granted (where will be "the bar"?), and that the availabilities in enough quantities remain to be determined (likely rising initially over months). Also, the first vaccines will probably be reserved for the care givers and the populations at higher risks, starting with the elderlies. Some vaccines are expected only later in 2021 (e.g. Sanofi / GSK or Valneva), in contrast to the first ones potentially being delivered as soon as Q4 2020 (AstraZeneca). One may also ask how the concurrent orders from the US, Europe, Japan, and other geographies will be arbitrated by each company in terms of priority (all eyes on the "US first"). Whereas some companies have pledged for simultaneous availability of their vaccines everywhere in the world (Sanofi, after a controversial statement), it remains to be seen how it will materialize. As the pandemic is global, it requires a global answer.
Concerning the rest of the world, two Chinese companies are among the most advanced (Sinovac, Sinopharm), whereas some of the pharma names mentioned for the developed countries have already signed deal with local players to supply China (e.g. AstraZeneca with Kangtai Biologics). Russia recently made a highly publized announcement on its own Sputnik V program. For the low & middle income countries, some of the most advanced companies have already inked important deals to bring a worldwide equitable access to their COVID vaccines (e.g. AstraZeneca with Serum Institute of India, with the support of CEPI & Gavi). We will finally mention the COVAX initiative, "a global initiative aimed at working with vaccine manufacturers to provide countries worldwide equitable access to safe and effective vaccines, once they are licensed and approved", with a press release out yesterday. It is co-led by CEPI, Gavi, the Vaccine Alliance, and the World Health Organization (WHO). 172 countries have engaged discussions to potentially participate in the COVAX initiative, representing more than 70% of the world's population. Some key agreements are also mentioned in the WHO's press release.
A collaboration between Serum Institute of India (SII), Gavi and the Bill & Melinda Gates Foundation announced earlier this month will ensure up to 100 million doses of AstraZeneca or Novavax's candidate vaccines, if successful, will be available to low- and middle-income economies through the COVAX Facility at just US$ 3 per dose. The arrangement also provides an option to secure additional doses if COVAX sees a need for it. Separate agreements between Gavi, CEPI and AstraZeneca, announced in June, guarantee a further 300 million doses of their candidate vaccine, if successful, for the COVAX Facility.
So far, Japan has booked between 1 and 2 course per inhabitant so far, only focusing on a few players (3 agreements). The US have signed initial contracts for approximately 1.5 course per inhabitant (6 agreements), versus around 1.25 course per inhabitant for the EU Member States (5 agreements, including the one announced yesterday between Moderna and the EC). The Swiss Federal State currently lags, with only around 0.25 course secured per inhabitant.
In terms of pre-order quantities (Table 3) from the developed countries -approximately 1 billion people-, the clear winner so far is AstraZeneca, collecting the largest number of initial doses of their vaccine ("up to" 820 million), far ahead of the vaccine experts' duo composed of Sanofi and GSK, with 460 million doses. AstraZeneca made an early and opportunistic move when they licensed "the Oxford vaccine" late in April, since they are not a vaccine-oriented pharma company. Moreover, the ChadOx1 platform was never used in an approved vaccine. Seeing Sanofi / GSK so high might come as a surprise, since they have not even entered the clinics yet, but the developed countries are probably "playing the security" as these are experienced companies in the vaccine area, but also because of the manufacturing capacities of these two companies, which could lead to a faster manufacturing ramp up than with other candidates that would be approved before them. Moderna Therapeutics is currently the laggard in the leading group, with "only" around 185 million doses in the order book, despite being one of the most advanced candidates, timing-wise. However, Moderna could catchup with the optional orders ("up to" 480 million doses), more or less on par with those from both Sanofi / GSK and Pfizer / BioNTech ("up to" 500 million doses each). Globally, the maximum total doses are unsurprisingly ordered from the largest pharma companies: between 900 and 1 billion doses for AstraZeneca and Sanofi / GSK, and around 750 million doses for Johnson & Johnson and Pfizer / BioNTech.
Overall, this is not less than 2.7 billion initial doses that could be confirmed in the next months, with a grand total of almost 5 billion doses. While some analysts have recently pushed the market size estimates for the COVID vaccines up to 100 billion USD, this estimate seems nevertheless very optimistic.
Beyond the purpose of just making a statement on an approval of a vaccine before a given date, namely the US Presidential elections, the actual availability for the general public will not be instantaneous, even in the US. And this despite the efforts of the companies to start "at risk" production as soon as possible. Though, one might already anticipate a flood of videos in the media of people receiving a vaccine, especially if it comes before the elections. Therefore, the authorities will also have to manage the expectations of the public who, at least for some, will want a vaccine right after approval. The strategies to address the deployment of the vaccination policies have to be determined and communicated in advance to educate the public. By the way, is there even a consensus on who will have to be vaccinated (e.g. down to which age)? One of the big challenges might also be to convince the most people to get vaccinated, praying for an absence of any bad buzz on the safety and tolerability. But as mentioned by several experts (see the Bill Gates interview above mentioned), we would not need everyone to be vaccinated to stop the exponential proliferation of the virus, providing that the vaccines actually provide a protective immunity. It seems that a 30-60% "herd immunity" would be enough to reach that goal, but it does not mean that we have to stop vaccinations once we reached these levels. Moreover, despite early promising immunogenicity data, there are still question marks about the level of protection of the vaccines (to be determined from clinical trials), and on the durability of protection (what are the surrogates, given that we will not have long-term data at the time of approvals?). Lastly, if it happens one may have the chance to pick between a vaccine and another, which one would be the best choice?
Conflict of interests: at the moment of initial publication (25/08/2020), the author of this post, Bertrand Delsuc, owns shares in some companies mentioned in this post (Valneva - no significant ownership). The data in this post are no investment recommendations.