As the year winds down, the top companies in the COVID-19 vaccine race are nearing the finish line in the United States and other countries around the world.
On November 20, Pfizer and BioNTech submitted an application for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration (FDA) for their COVID-19 vaccine. Yesterday, Moderna did the same thing. If all things go well, the Pfizer-BioNTech vaccine will receive EUA around December 10 or within a few days after, and the Moderna vaccine will receive EUA around December 17 or within a few days after. Pfizer and BioNTech, who are handling distribution themselves rather than through McKesson, which is the designated handler for the U.S. government’s Operation Warp Speed, have indicated they will begin distribution within 24 hours of authorization. Moderna has indicated a similar turnaround via McKesson.
Meanwhile, they are also continuing rolling submissions in Europe and other countries. Moderna has already begun a rolling review process with the European Medicines Agency (EMA), Health Canada, SwissMedic, the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA), Ministry of Health in Israel, and Health Sciences Authority in Singapore. Moderna also plans to seek Prequalified (PQ) and/or Emergency Use Listing (EUL) with the World Health Organization (WHO).
The EMA indicated today that it would issue an opinion on the Pfizer-BioNTech vaccine within weeks and has a meeting scheduled for December 29, at the latest. The rolling review process began on October 6, which allowed European regulators to evaluate the data as it was submitted.
The UK issued a special rule to allow its regulatory system to bypass the EMA, which might make it the first to issue Emergency Use Authorization for the Pfizer-BioNTech vaccine. If the EMA grants conditional clearance, the vaccines might be available in Europe before the end of the year.
The UK has placed a lot of their emphasis on the AstraZeneca-University of Oxford vaccine and the Pfizer-BioNTech vaccine. The AstraZeneca-Oxford product had demonstrated an efficacy rate between about 62% and 90%, but there were issues with the Phase III trial. In a group of about 2,800 patients, they were accidentally dosed with a half-dose of the initial shot. Oddly, that group had the 90% efficacy data, which is still not fully understood. One of the groups with two full doses a month apart demonstrated 62% efficacy. The combined analysis averaged 70%. These levels are still good, but far below the 94-95% efficacy seen in the other two vaccine products.
AstraZeneca has indicated it plans to conduct another trial to validate the 90% efficacy half-dose regimen. This particular disparity isn’t expected to delay approvals in the UK and European Union, but would probably slow it down in the U.S.
At this time, Russia and China have broadly distributed their own vaccines, but have not been very transparent about their processes. The Russian vaccine in particular, dubbed Sputnik V, has raised questions because it began wide inoculations before even beginning a Phase III trial.
Although the UK regulators tend to be tough and have refused to confirm the fast timelines by some politicians and officials, UK Prime Minister Boris Johnson said yesterday, “This could—could, if we’re lucky, if everything goes right—be available just in a few weeks.”
The UK regulators have begun analyzing the Pfizer vaccine data and is expected to begin evaluating the AstraZeneca product soon. They are already evaluating the Moderna vaccine, but don’t believe it would be available in Britain and wider Europe until spring.
Meanwhile, polls have suggested, in the U.S., at least, that anywhere from half to two-thirds of Americans are reluctant to get the vaccine.
Heidi Larson, director of the Vaccine Confidence Project and author of the book Stuck: How Vaccine Rumors Start and Why They Don’t Go Away, told NPR, that the distrust seems to broadly fall into people who believe a vaccine is “not natural,” and others that are afraid of its “newness.” She went on to say, “For something new and unfamiliar, particularly in this hyper uncertain environment where every day you wake up and you’re not sure what the guidance is going to be, that creates anxiety.”
Although no one has yet to have an approved product with the mRNA technology that it is using for the COVID-19 vaccine, Moderna has accumulated a significant amount of data on their approach’s safety with other pipeline vaccines. For example, in April 2020, they released promising early data from a Phase I trial of its experimental Zika vaccine. Zika virus is transmitted primarily by Aedes mosquitos. The interim Phase I data evaluated four different dose levels and demonstrated no vaccine-related serious adverse events (SAEs) or adverse events of special interest (AESI). Like the COVID-19 vaccine, the vaccine uses mRNA, two doses 28 days apart, and a similar nanoparticle delivery system.
As of April, Moderna had conducted early safety clinical trial success on nine vaccine candidates, including respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and parainfluenza virus (PIV3), influenza H7N9, cytomegalovirus (XCMV), Zika, Epstein-Barr, chikungunya, and now COVID-19.
Similarly, BioNTech, who developed the vaccine it is advancing with Pfizer, has a pipeline including vaccines for melanoma, prostate cancer, HPV16+ head and neck cancer and other cancers, and influenza, HIV, tuberculosis and or course, COVID-19.
The AstraZeneca and University of Oxford group had an early start back in April, largely because Oxford’s Jenner Institute had begun testing a vaccine for an earlier coronavirus in 2019, demonstrating the vaccine was not harmful to humans. It had also been tested in six rhesus macaque monkeys at the National Institutes of Health’s Rocky Mountain Laboratory in Montana. As early as 2014, researchers at Jenner had developed a template for mass production of the coronavirus vaccine. Once the pandemic gathered steam, the group shifted its previous work to focus on COVID-19.
The AstraZeneca-Oxford vaccine leverages a viral vector using a weakened version of a common cold (adenovirus) virus that contains the genetic materials of SARS-CoV-2 spike protein. The adenovirus is what is typically used in gene therapies.
Some vaccine skeptics are concerned that the entire process has been rushed, but Larson points out that what has been shortened in most cases are administrative steps. “We have new technologies, but the steps involving safety have not been shortened. They have not been compromised. And no vaccine will be delivered to the public before it really has enough confidence. And most importantly on the safety, no company wants a bad vaccine. No government wants a bad vaccine. No individual wants a bad vaccine. It’s not in anyone’s interest.”
In addition, most vaccine clinical trials require that people in the trials be diagnosed with whatever they are being vaccinated against. That’s relatively fast in a pandemic as widespread as COVID-19, but can be much more difficult and take far longer if there are few active cases of the disease in the population. Approvals for each phase of a trial can take weeks, months, or even years, but with the urgency of the COVID-19 pandemic, companies and regulators have moved to design and approve study designs as quickly as possible, which has significantly shortened the development process without compromising safety.
