The COVID Vaccine Race

Competitors, current progress and the EU’s position

It has now been several months since the COVID-19 pandemic took the entire globe by storm. One after the other, the world’s countries saw themselves compelled to shut down, freezing their economic activity and locking their people at home, with seemingly no other protection against the uncontrollable spread of the new virus than to curl up in defence like a hedgehog and wait for a vaccine to come. And today, after months of wait, fear and hope, it finally seems that a COVID-19 vaccine could be coming soon. Indeed, in the past weeks a number of big pharmaceutical companies have stepped up and declared they now are in an advanced phase of the development of a vaccine: from one day to the next, we were flooded with news on clinical trials, Phase 1, 2, 3, and continuous relaunches of higher efficiency percentages from all sides – in what now is a full-blown “vaccine race”.

Let’s try to shed some light on this seemingly chaotic race, by illustrating who are the different competitors, which development phase their respective vaccines are now at, what are the future projections for a vaccine to be available globally, and, last but not least, where the European Union stands in all of this.

The Main Competitors

Oxford University / AstraZeneca PLC: The world-famous university and the British-Swedish multinational biopharmaceutical company headquartered in Cambridge first announced their collaboration for the development of a COVID-19 vaccine in April 2020.

The research phase, developmental studies and trials are being carried out by a team of experts from both parties at the Jenner Institute and the Oxford Vaccine Group, while AstraZeneca will be responsible for the worldwide manufacturing and distribution of the chosen formula.

BioNTech SE / Pfizer Inc.: BioNTech SE is a German biotechnology company founded in 2008 and headquartered in Mainz. Up until it stepped into the limelight with the COVID vaccine race, its main research area was cancer immunotherapy. Pfizer Inc. is an American multinational pharmaceutical corporation headquartered in New York City, among the world’s largest in reach and revenue.

The two companies officially announced their partnership for a COVID-19 vaccine development in March 2020. BioNTech takes care of the development and trials in Germany, while Pfizer of trials in the US, large-scale manufacturing and global distribution.

Moderna: an American biotechnology company of relatively young foundation (2010) based in Cambridge, Massachusetts. It develops drugs and vaccines based exclusively on mRNA techniques. Moderna first announced it had started working on an RNA-based vaccine against COVID-19 in late January 2020.

CanSino Biologics: a Chinese vaccine company founded in 2009 and headquartered in Tianjin. It is already known in the medical world for having played a key role in the development of the Ebola vaccine during the 2013 epidemic (in collaboration with the National Research Council of Canada).

They first announced their commitment to the development of a COVID vaccine in February 2020, with the Chinese Academy of Military Medical Sciences as a research partner.

Gamaleya: the Gamaleya Research Institute, a branch of the Russian Ministry of Health. It joined the race relatively late, in June 2020. Its vaccine project was dubbed “Sputnik V”.

The 6 Phases of Vaccine Development

Pre-Clinical Trials: Scientists firstly develop the new vaccine in vitro, using natural or synthetic antigens, then test it on single cells and then on animals – especially mice and Rhesus monkeys – to verify if it produces the immune response sought in humans.

Phase 1 – Safety Trials: the vaccine is given to a small sample of adult human subjects. The main aims here are to test correct dosage, to confirm that it stimulates the human immune system in the sought way, and to test first reactions and safety.

Phase 2 – Expanded Trials: the sample is expanded to at least a few hundred people, split in different age groups (often just separating the elderly) to see if the vaccine elicits a different immune reaction in them. The final aims are to determine the most effective dose, identify common side effects and try to limit them.

Phase 3 – Efficacy Trials: the sample is further expanded in the order of thousands, and randomly split into two groups as per the technique of Randomised Control Trials, or RCT: treatment group, who receives the vaccine, and control group, who receives a placebo. For obvious reasons of bias prevention, participants do not know which group they were randomised into. The aim of Phase 3 trials is to issue final results on the effectiveness of the vaccine, while having precise information on its effects on different age groups and keeping side effects to a minimum.

In June, the FDA advised that vaccines submitted to it for authorisation had to show robust results of 50% effectiveness at the very minimum.

Limited or Early Approval: can be granted by the health authorities of a certain country for early limited use within it, just under special circumstances or under the request of “emergency authorisation”.

Final Approval: allows licensing for general use. Needs to begranted by the health authorities of all countries the vaccine is going to be distributed in, by the regulatory authorities implementing internationally recognised standards (e.g. the FDA) and by global health authorities (e.g. the WHO).

Source: The New York Times

The Competitors’ Progress

Oxford / AstraZeneca:

Pre-Clinical Trials – At the moment of the announcement in April, AstraZeneca stated that pre-clinical trials had already proven successful to an encouraging degree, and that they were already set to move on to Phase 1.

Phase 1 and 2 – First updates were issued in late July. 95% of the participants who were administered at first one and then two doses showed a robust immune response with “a four-fold increase in antibodies to the virus”. Side effects included headache, strong fatigue, chills, some feverishness and diffused muscle ache, but nothing that couldn’t be countered with rather basic painkillers and paracetamol treatments.,

In Phase 2, particular attention was devoted to the effect of the vaccine on the elderly, with 240 out of 560 people in the first Phase 2 sample being over 70. The vaccine was found effective in raising immunodefences not only against COVID-19, but also against other immune diseases.

Phase 3 – Phase 3 studies broke down the volunteer pool into several age groups, studying in detail how each responded to the vaccine. Results were very promising until global trials had to be brought to a halt for safety checks in early September, after a British volunteer developed a severe inflammation and a Brazilian one died. Shortly after, studies resumed, and preliminary results encouragingly showed that older volunteers produced as many antibodies against the coronavirus as the younger ones.

On November 5th the CEO of AstraZeneca, Pascal Soriot, stated that official Phase 3 results are expected by the end of this December.

BioNTech / Pfizer:

Pre-Clinical Trials – The first results came in April, one month after the announcement of the partnership. They proved close to 100% effective in preventing respiratory infections and creating a sufficient amount of antibodies.

Phase 1 and 2 – Launched in May, it included studies on two versions of a mRNA-based vaccine. They found that while both versions caused volunteers to produce strong antibodies against the virus, only one of them produced significantly fewer and milder side effects (fatigue, fever and little else). Thus, the other version was dropped, and only the latter was carried into Phase 3.

Phase 3 – Slowed down by the rather chaotic period of the US presidential elections (with President Trump often instrumentalising Pfizer’s vaccine and spreading incorrect news on its future availability), Pfizer was finally able to publish preliminary results of over 90% effectiveness at the beginning of November: no other company had achieved such results before.

Eventually, on November 18th they issued triumphant final results, according to which the vaccine was 95% effective on average, with the percentage dropping only by 1% (94%) among over-65 years old volunteers, who often have the weaker response to vaccines. Additionally, no serious side effects were detected.

Limited Approval – On the basis of these strong Phase 3 results, BioNTech/Pfizer has now submitted a request for an “emergency use authorisation” to the FDA, which would allow a first limited pool of Americans to get the vaccine by the middle of December. Negotiations for European authorisation are currently underway.

Moderna:

Pre-Clinical Trials – Three different techniques were adopted: low dose, high dose and, peculiarly, the insertion of drops of virus directly in the nose, to simulate the situation in the airways of gravely infected people. Trials were completed at the beginning of March.

Phase 1 and 2 – Phase 1 began in late March, with the partnership of the US National Institute of Health (NIH) and the aid of substantial US government funding – nearly $1 billion. Volunteers were administered 2 shots each, in high, medium or low dose. After the second dose, all participants showed high levels of antibodies and virus neutralisation, with the best results in the high-dose group; however, more than half of the participant reported persistent side effects, and 3 had severe ones. Moreover, after the publication of the results, governmental experts accused Moderna of not disclosing more specific critical data.

Phase 3 – Moderna brought forward to this phase only the low-dose vaccine, deemed the safest since it caused the fewest side effects. 30,000 volunteers were divided into two groups: a treatment group who received two doses of the vaccine, and a control group receiving a placebo.

On November 16th, Moderna announced preliminary results of more than 90% effectiveness, joining BioNTech / Pfizer at the forefront of the race only a week later. Just a few days later, they officially confirmed 94.5% effectiveness. The vaccine also appears to prevent the disease from developing in its most severe forms. Moreover, a comparative advantage the Moderna vaccine has with respect to BioNTech / Pfizer is a longer expected shelf life and storage temperatures not as low: -20 against -70 degrees Celsius.

Limited Approval – Similarly to BioNTech / Pfizer, Moderna is planning to submit to the FDA an application for “emergency use authorisation” in the next few weeks. Officials talked about 20 million doses for the United States being available by mid-December, with high-risk groups being the priority.

CanSino Biologics:

Pre-Clinical Trials – led in relative silence, without many updates being published. The company preferred short early efficacy tests and was eager to move on to Phase 1, also because of its closeness to the epicenter of the pandemic in Wuhan.

Phase 1 and 2 – Phase 1 began in mid-March, interestingly in Wuhan itself, with trials on 108 healthy volunteers aged from 18 to 60. A single dose of the vaccine led to sufficient antibody production within 2 weeks; however, since the volunteers were all healthy people from Wuhan, it was argued that they could well have developed powerful antibodies prior to the vaccine. Phase 2 extended the sample to more than 500 volunteers, who were divided into treatment and placebo group. The first results, issued in July, reported that 85% of the participants successfully produced and maintained antibodies; however, 70% also showed some degree of adverse reaction.

Phase 3 – Starting from early August, CanSino began delocalising Phase 3 trials to Saudi Arabia, Pakistan, Russia and Mexico. The first results are awaited by the end of this year.

Special Approval – In an unprecedented move, the Chinese military approved the vaccine on June 25th as a “specially needed drug.” CanSino would not say whether vaccination would be mandatory or optional for soldiers.

Gamaleya:

Pre-Clinical Trials – similarly to CanSino, led in relative silence, under the label of “governmental project”. In June, Russian health minister Mikhail Murashko publicly announced that a vaccine was indeed in the works and that clinical trials had been completed successfully, ready to move on to Phase 1.

Phase 1 and 2 – Gamaleya reused a vaccine design that they had previously developed and tested for MERS, a disease caused by a virus of the same strain. The results showed acceptable levels of antibodies and only mild side effects. However, it was not proven whether vaccinated people are less likely to become infected in the first place than those who aren’t. Moreover, there were leaks on doctors testing the vaccine on themselves, an extremely risky practice if true. Finally, Russian President Vladimir Putin also added fuel to the fire by announcing in early August that Russian healthcare regulators had approved the vaccine for distribution, before Phase 3 trials had even begun.

Phase 3 – begun in late August, with a sample expanded from 2,000 volunteers to 40,000, through recruitment campaigns also launched in Belarus, the UAE and Venezuela. The sample was again split into a treatment and a placebo group. The first results were published on November 11th, declaring 92% effectiveness. However, the most part of the scientific community remains skeptical, on one hand believing that such results are just partial, rushed out to match the announcements of competitors BioNTech / Pfizer and Moderna, and on the other still harbouring doubts on the transparency and ethics of the whole process.

The EU’s Position

On November 11th, the European Commission officially announced that it had approved “a contract with pharmaceutical companies BioNTech and Pfizer, which provides for the initial purchase of 200 million doses on behalf of all EU Member States, plus an option to request up to a further 100 million doses, to be supplied once a vaccine has proven to be safe and effective against COVID-19”.

Such contract is already the fourth one stipulated by the Union to order for large-scale production and distribution of a COVID vaccine in Europe, after the preliminary ones with AstraZeneca, Sanofi-GSK and Janssen Pharmaceuticals.

On November 19th, after the EU Leaders’ videoconference held on that day, President von der Leyen confirmed that a fifth contract has also been struck with CureVac, while negotiations with Moderna are now approaching their final stage: we can thus expect the number of contracts to increase to six very soon.

The reason for signing so many contracts is simple: the EU is seeking to have the choice between a series of vaccine alternatives as varied as possible, produced with different processes and technologies. Indeed, the far-sighted goal for the future is to be able to pick the one that will prove safer and most effective once all the trial periods will be concluded and comparable effectiveness results will be available.