The estimate, which is based on past vaccination rates of other vaccines, considered pricing and vaccination trends and expected demand for any new COVID-19 vaccine. It is a high "best case" estimate, the firm said. The high COVID-19 vaccination rate estimate, based on past influenza vaccinations rates, is 76% in the U.S and 21% in the global population. This accounts for generally lower vaccination rates outside the U.S., Europe, and Japan.

Bruce Carlson from Kalorama Information.

The firm also computed a low estimate of $12 billion, based on limited compliance with vaccination recommendations, which assumes a vaccination rate of 47% in the U.S. but only 9% in the global population.

Since the onset of the COVID-19 pandemic, many governments have started stockpiling orders for COVID-19 vaccines, creating a small "premarket" for the products ahead of regulatory approval, which is already valued at over $108 billion in late 2020. Kalorama analysts' caveat is that this is not money in the bank -- that the contracts are based on successful clinical development, emergency use authorization (EUA) approval, and manufacturing success. If any one of these factors fails, then manufacturers would miss out on market share.

There are currently no known vaccines or specific antiviral treatments for COVID-19. However, development activities in this area are unprecedented. There are over 200 confirmed COVID-19 vaccine candidates of which many have already entered clinical trials. Regionally, the U.S. shares 20% of COVID-19 vaccine development activities globally, followed by China with 8%, and France with 6%.

According to Kalorama's report, current COVID-19 vaccine candidates under development primarily use protein and non-replicating viral vector platforms. But there are also a substantial number of RNA-based, virus-like particle-based, and replicating viral-vector-based COVID-19 vaccines under development.

Despite ongoing clinical development, several countries have secured preorders of multiple vaccines – essentially covering several potential candidate approvals. Countries such as the U.S., U.K., Canada, and Japan have secured contracts well above the number of doses needed for each country's entire population, continuing to highlight the potential for some candidates to not reach market. For example, the U.S. leads in vaccine doses to population at 8.12 per capita, meaning that the country has secured eight vaccine doses per person.

The report authors noted that secured contracts may not be fulfilled, due to regulatory or manufacturing complications. Moreover, many COVID-19 vaccine candidates under development require a two-dose regimen. In this case, contracts will provide vaccinations for half of the total number of secured doses.

Listed below are recent development activities of the leading COVID-19 vaccine candidates.

Moderna offers its messenger RNA (mRNA)-1273, a novel lipid nanoparticle-encapsulated mRNA vaccine encoding for a perfusion stabilized form of the spike (S) protein. On October 22, 2020, Moderna announced it completed enrollment of its phase III Coronavirus Efficacy (COVE) study of the mRNA vaccine against COVID-19.

AstraZeneca, in collaboration with the University of Oxford, is evaluating the COVID-19 vaccine candidate AZD1222 in phase III clinical trials. AZD1222 was co-invented by the University of Oxford and its spin-out company, Vaccitech. It uses a replication-deficient chimpanzee adenovirus that contains the SARS-CoV-2 virus S protein. On September 9, 2020, the company announced a temporary pause for AZD1222 development, citing time to allow an independent committee to review the safety data of a single event of an unexplained illness that occurred in the U.K. phase III trial. On September 12, 2020, the committee concluded its investigations and recommended that trials in the U.K. were safe to resume. Trials resumed in the U.K., Brazil, South Africa, and India following the announcement. On October 2, 2020, trials resumed in Japan and in the U.S. on October 22, 2020.

In March 2020, BioNTech and Pfizer signed an agreement for the co-development and distribution (excluding China) for BNT162b2, based on BioNTech's proprietary mRNA technology and supported by Pfizer's global vaccine development and manufacturing capabilities. It encodes an optimized SARS-CoV-2 full-length spike glycoprotein (S), which is a target of virus neutralizing antibodies. The vaccine candidate is currently being evaluated in a global phase III study ongoing at more than 120 clinical sites worldwide. Throughout October 2020, BioNTech and Pfizer announced rolling submissions to various regulatory bodies, including Health Canada and European Medicines Agency, for the candidate.

Janssen Pharmaceutical Companies responded to the outbreak to develop a possible preventive vaccine candidate against SARS-CoV-2, leveraging Janssen's AdVac and Per C6 technology. On September 23, 2020, Johnson & Johnson/Janssen Pharmaceutical announced the launch of its large-scale, pivotal, multicountry phase III Ensemble trial for its COVID-19 vaccine candidate, JNJ-78436735. However, as of October 13, 2020, it had temporarily paused all dosing for its vaccine candidate due to an unexplained illness in a study participant. On October 23, 2020, Johnson & Johnson announced in an updated statement that it is preparing to resume recruitment in the pivotal phase III Ensemble trial of its investigational Janssen COVID-19 vaccine in the U.S. after the temporary pause.

GlaxoSmithKline (GSK) and Sanofi Pasteur signed a vaccine collaboration for COVID-19 technologies in April 2020 with a goal of commercializing a safe and effective vaccine in the second half of 2021. On September 3, 2020, Sanofi and GSK announced the initiation of a phase I/II clinical trial.

• In July 2020, GSK signed another development collaboration agreement with Medicago for a novel adjuvanted COVID-19 candidate vaccine. The agreement combines Medicago's recombinant Coronavirus Virus-Like Particles (CoVLP) with GSK's pandemic adjuvant system.
• In February 2020, GSK entered a research collaboration with Clover Biopharmaceuticals to evaluate Clover's protein-based coronavirus vaccines candidate, COVID-19 S-Trimer vaccine candidate with pandemic adjuvant system. Clover Biopharmaceuticals is a Chinese biotech company focused on novel biologic therapies and its protein-based coronavirus vaccines candidate, COVID-19 S-Trimer. In June 2020, the GSK/Clover vaccine candidate entered phase I clinical trials.
• Additionally, GSK entered into a collaboration with the Coalition for Epidemic Preparedness (CEPI) focused on the development of a vaccine for COVID-19. The first agreement to formalize this arrangement has been signed between GSK and the University of Queensland, Australia, which entered a partnering agreement with CEPI in January 2019 to develop a "molecular clamp" vaccine platform, intended to enable targeted and rapid vaccine production against multiple viral pathogens.

There are several uncertainties in this market segment which are continuing to change and evolve daily. However, Kalorama Information has evaluated the potential market beginning in 2021 using influenza vaccine models, current pricing trends and other factors which will be the key points shaping the market.

Bruce Carlson is the publisher of Kalorama Information, part of Science and Medicine Group.

Disclosure: Kalorama Information is a sister company of The Science Advisory Board.