Gianna is an associate editor of The American Journal of Managed Care® (AJMC®). She has been working on AJMC® since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey.
In the span of a few weeks, Pfizer, Moderna, and AstraZeneca all announced positive results from their respective coronavirus disease 2019 (COVID-19) vaccine trials, with Pfizer submitting to FDA for an emergency use authorization (EUA) on November 20.
In the span of a few weeks, Pfizer, Moderna, and AstraZeneca all announced positive results from their respective coronavirus disease 2019 (COVID-19) vaccine trials, with Pfizer submitting to FDA for an emergency use authorization (EUA) on November 20. To receive approval, the FDA requires coronavirus vaccines be at least 50% effective.
However, each vaccine is distinct when it comes to efficacy, storage, dosing, and production. In addition, according to the CDC, “vaccine doses purchased with US taxpayer dollars will be given to the American people at no cost. However, vaccination providers will be able to charge an administration fee for giving the shot to someone.”
Regardless of which vaccine gets approved, the first doses administered in the United States will be distributed to health workers, followed by vulnerable populations over 65 years old or with medical conditions and essential workers. At a time when COVID-19 cases continue to surge throughout the country, the announcements offer hope that the pandemic's end may soon be in sight.
On November 9, Pfizer and BioNTech were the first companies to announce results of their late-stage trial on more than 43,000 participants, which initially showed the vaccine was 90% effective. But final analyses of the phase 3 trial showed the vaccine was in fact 95% effective in preventing COVID-19, was safe and appeared to fend off severe disease, CNBC reported. The study evaluated 170 confirmed infections among participants recruited from over 100 clinical sites around the world. A total of 162 cases occurred in the placebo arm, compared with 8 cases observed in the vaccine group. No serious safety concerns have been reported to date.
The vaccine is administered in 2 doses 3 weeks apart while protection is achieved 28 days after the first shot. The EUA submission included safety data on about 100 children aged 12 to 15. Roughly 43% of global trial participants and 30% of US participants have racially diverse backgrounds, and 41% of global and 45% of US participants are aged 56 to 85. Depending on an approval date, the immunization could be available for high-risk US populations by the middle to end of December 2020.
The vaccine, BNT162b2, contains messenger RNA (mRNA) which is thought to provoke the immune system to fight the virus, but requires a storage temperature of –94° Fahrenheit (F). This could lead to logistical concerns during distribution as most doctors’ offices do not have freezers that go that low. The vaccine needs to be kept so cold because the mRNA is more likely to break apart at above freezing temperatures. To help mitigate these concerns, Pfizer developed specially designed temperature-controlled shippers which can maintain storage conditions for up to 15 days. After being thawed, the vaccine vial can be stored for up to 5 days in refrigerated conditions (35.6° to 46.4° F).
“Based on current projections, the companies expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021; the companies will be ready to distribute the vaccine within hours after authorization,” a joint statement reads. In July, HHS and the Department of Defense partnered with the companies, offering Pfizer $1.95 billion upon manufacturing the first 100 million doses should the vaccine be approved. The vaccine will be manufactured in-house by the companies.
A decision on the EUA could be made as early as December 10, CNN reported.
Following the Pfizer/BioNTech announcement, Moderna reported preliminary results from its COVID-19 vaccine trial on November 16. The phase 3 COVE study, which enrolled more than 30,000 participants in the United States, found the company’s experimental vaccine to be 94.5% effective. Results from the first interim analysis was based on 95 reported cases of COVID-19, of which 90 occurred in the placebo group and 5 in the vaccine arm. None of the infected patients who received the vaccine developed severe cases of COVID-19, compared with 11 participants in the placebo arm who did.
The vaccine is similar to Pfizer’s in that it also includes mRNA, but no mRNA vaccine has been approved or marketed for any disease, The New York Times reported. Moderna’s mRNA-1273 is also administered in 2 doses 4 weeks apart. No significant safety concerns have been reported throughout the trial. All participants are aged 18 years or older while more than 7000 are over the age of 65. Medically high-risk groups account for 42% of the population in the study and 37% of participants come from communities of color.
Although both candidates are composed of mRNA, Moderna’s vaccine differs significantly from Pfizer’s in that it can be stored in –4° F (equal to most home or medical freezer temperatures) for up to 6 months. In addition, the vaccine remains stable at 36° to 46°F, the temperature of a standard home or medical refrigerator, for 30 days. It will also last for 12 hours at room temperature. The 2 vaccines’ temperature requirements differ due to different proprietary formulations of fat used to encase and protect the mRNA.
Moderna plans to submit an EUA to the FDA in the coming weeks. Should the vaccine gain approval, Moderna estimates it will have approximately 20 million doses ready to ship in the United States by the end of 2020. In 2021, the company hopes to manufacture between 500 million and 1 billion doses globally.
The Biomedical Advanced Research and Development Authority (BARDA) “is supporting the continued research and development of mRNA-1273 with $955 million in federal funding,” according to a Moderna statement. The Authority is also “reimbursing Moderna for 100% of the allowable costs incurred by the company for conducting the program described in the BARDA contract. The U.S. government has agreed to provide up to $1.525 billion to purchase supply of mRNA-1273 under U.S. Department of Defense Contract No. W911QY-20-C-0100.”
AstraZeneca is the latest pharmaceutical company to release results from its COVID-19 trial. On November 23, the company announced its vaccine, developed by Oxford University, could be approximately 90% effective when administered as a half dose followed by a full dose at least a month later. According to Reuters, the vaccine prevented an average of 70% of COVID-19 cases in late-stage trials in Britain and Brazil. However, if the full dose was given twice one month apart, the efficacy was 62%. A total of 11,636 individuals of the 23,000 trial participants received a vaccine while the remainder received a placebo. No serious safety events or severe cases of COVID-19 were reported throughout the trial.
By the end of 2020 the company hopes to have 200 million doses ready, nearly 4 times as many as Pfizer plans to develop. AstraZeneca also estimated nearly 700 million doses of the vaccine could be ready globally by the end of the first quarter of 2021. Overall, the vaccine is cheaper than Pfizer's and Moderna’s as it uses more conventional technology. Specifically, it “uses a modified version of a chimpanzee cold virus to deliver instructions to cells to fight the target virus,” Reuters reported. It can also be transported and stored at normal refrigerator temperatures (36° to 46° F).
AstraZeneca has set the price at around $2.50 a dose compared with Pfizer’s $20 and Moderna’s $15 to $25, the Associated Press reported. Because it is cheaper and easier to store, the vaccine can be rolled-out faster in poorer countries and can be more widely distributed. Because the smaller initial dose is more effective than the larger dose, it may reduce costs and mean more individuals can be vaccinated with the vaccine supply already manufactured.
However, the preliminary data did not reveal how many individuals of the 131 cases of COVID-19 in the study received the smaller initial dose to form the basis of the 90% efficacy claim. Data presented thus far did not meet requirements set by US regulators. But the company plans to prepare regulatory submission of the data to authorities around the world for early approval. AstraZeneca also hopes to seek an emergency use listing from the World Health Organization so the vaccine can become available in low-income countries.