The year 2020 has proven to be a defining year for the medical and biopharmaceutical fields across the world. Since the first half of the year, many countries across the world have been plagued with the COVID-19 pandemic. With countries now facing second and third waves of COVID-19 outbreaks and the total number of cases across the world reaching close to 60 million at the point of writing this article, biopharmaceutical companies race against time to search for a safe and efficacious vaccine that could help combat against the COVID-19 disease.

The last few months of 2020 has seen much promise in the area of vaccine clinical trials against COVID-19.  A number of bio pharmaceuticals companies have announced success in their Phase 3 clinical trials. These results bring hope to the potential of a vaccine against COVID-19 in the near future. At the time of writing, there are 60 COVID-19 vaccines in the clinical development stage and 172 in the pre-clinical development stage. This article will provide a summary of the notable biopharmaceutical companies that have released results from its Phase 3 clinical trial for the COVID-19 vaccine and national regulatory approval across the world. The information in this article is based on clinical trial results released as of December 2020 and companies mentioned here are not ranked in any order.

Moderna. Inc.

Vaccine Candidate: mRNA-1273, LNP-encapsulated mRNA

Vaccine Platform: RNA

Dosage: 2 doses, one at 0 and 28 days

Since the reveal of the genetic sequence of the novel coronavirus by the Chinese authorities on 11 January 2020, Moderna quickly kick-started its quest towards development of a vaccine against COVID-19. Within days, on 13 January 2020, Moderna finalised the sequence for mRNA-1273 with the intention of the National Institute of Allergy and Infectious Disease (NIAID) to begin Phase I studies for mRNA-1273 against SARS-CoV-2. Following the success of Phase I and Phase II, Phase III clinical trial study of mRNA-1273 began promptly on 27 July 2020, in collaboration with NIH (National Institutes of Health) and BARDA (Biomedical Advanced Research and Development Authority).

The Phase III study completed an enrollment of 30,000 participants on 22 October 2020. On 16 November 2020, Moderna released an announcement that its Phase III study has met primary efficacy endpoints based on first interim analysis. Together with this, the first interim analysis that included 95 participants with confirmed cases of COVID-19 found to show statistically significant vaccine efficacy of 94.5 percent. Having scaled up its manufacturing for preparation of the COVID-19 vaccine, Moderna mentioned in a media release that by the end of 2020, it expects almost 20 million doses of the vaccine ready to ship to the U.S.

The Moderna COVID-19 vaccine was approved by the US Food and Drug Administration on 18 December 2020 for emergency use authorization which allows the distribution in the US for use in individuals 18 years of age and older.

AstraZeneca and Oxford University

Vaccine Candidate: AZD1222, ChAdOx1 nCoV-19

Vaccine Platform: Non-Replicating Viral Vector

Dosage: 2 doses, one at 0 and 28 days

On 30 April 2020, AstraZeneca and Oxford University announced an agreement for the collaboration to develop and distribute the recombinant adenovirus vaccine aimed at preventing COVID-19 infections.

The vaccine candidate, AZD1222/ ChAdOx1 nCoV-19 was developed by Oxford University’s Jenner Institute, together with the Oxford Vaccine Group. It is a replication-deficient chimpanzee viral vector based on a weakened version of the adenovirus that causes infections in chimpanzees and contains the genetic material of SARS-CoV-2 spike protein. Following a vaccination, the viral vector will produce surface spike protein, allowing the immune system to produce antibodies to fight against COVID-19 should it infect the body later.

Interim data from its Phase I/II trial demonstrated strong immune responses in all participants. These results were announced on 20 July 2020. This Phase I/II COV001 trial, led by Oxford University, found that AZD1222 was well tolerated coupled with robust immune responses against SARS-CoV-2. The blinded, multi-centre, randomised controlled Phase I/II trial with 1,077 healthy adult participants, aged 18-55 years. Results published in The Lancet also confirmed a single dose of AZD1222 resulted in a four-fold increase in antibodies to the SARS-CoV-2 virus spike protein in 95 percent of participants one month after injection. In all participants, a T-cell response was induced, peaking by day 14, and maintained two months after injection.

On 30 August 2020, AstraZeneca released a statement on the enrolment of 30,000 adults aged 18 and over to assess safety, efficacy and immunogenicity of AZD1222 in the U.S. This Phase III randomised, double-blind, placebo-controlled multi-centre study tested participants two doses of either AZD1222 or a saline control, four weeks apart, with twice as many participants receiving the potential vaccine than the saline control. 

The Phase III trials were paused for a month from September to October 2020 due to unexplained illness that occurred in the UK Phase III trial. Following resumption, interim data analysis announced on 23 November 2020 from Phase III trials in UK and Brazil demonstrated the vaccine to be highly effective in preventing COVID-19 with primary endpoints met and no hospitalisations or severe cases of the disease were reported in participants receiving the vaccine. There were a total of 131 COVID-19 cases in the interim analysis. Interim analysis of the four randomized controlled trials conducted in Brazil, South Africa and the UK were published in the Lancet on 8 December 2020.

The vaccine by AstraZeneca and Oxford University has received regulatory approval by the UK medical regulators on 30 December 2020.

BioNTech and Pfizer

Vaccine Candidate: BNT162b2, 3 LNP-mRNAs

Vaccine Platform: RNA

Dosage: 2 doses, one at 0 and 28 days

In a media release on 9 November 2020, Pfizer and BioNTech announced its first interim analysis from the Phase 3 clinical trial study of its COVID-19 vaccine. Based on the announcement, the vaccine candidate was found to be more than 90 percent effective in preventing COVID-19 in participants without evidence of prior SARS-CoV-2 infection.

The Phase 3 of the clinical trial began on 27 July 2020, enrolling a total of 43,538 participants, according to the interim Phase 3 results, no serious safety concerns were observed. Of all the participants, 38,955 of which received a second dose of the vaccine on 8 November 2020. Following the release of these results, the study continued to collect safety and efficacy data for the final analysis. Based on current projections we expect to produce globally up to 50 million vaccine doses in 2020 and up to 1.3 billion doses in 2021. Pfizer and BioNTech plan to submit data from the full Phase 3 trial for scientific peer-review publication.

On 2 December 2020, the BNT162b2 vaccine received the world’s first authorization for a vaccine against COVID-19. Regulatory agency in the UK, Medicines & Healthcare Products Regulatory Agency (MHRA) granted this temporary authorization for emergency use. This decision was based on data from the Phase 3 clinical study, which demonstrated a vaccine efficacy rate of 95 percent in participants without prior SARS-CoV2 infection (first primary objective) and also in participants with and without prior SARS-CoV-2 infection (second primary objective), in each case measured from 7 days after the second dose.

This mRNA vaccine by Pfizer and BioNTech later received authorization on 22 December 2020 in the European Union (EU), granting conditional marketing authorization and representing a milestone in a joint global effort to advance the first authorized mRNA vaccine. The vaccine has now been granted a conditional marketing authorization, emergency use authorization or temporary authorization in more than 40 countries worldwide, including all 27 EU member states.

As part of the agreement between Pfizer and BioNTech to provide global commitment to help address the COVID-19 pandemic, the two companies project an approximate 1.3 billion doses of the vaccine to be manufactured by the end of 2021.

References:

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-phase-3-cove-study-mrna-vaccine-against-covid

https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19

https://clinicaltrials.gov/ct2/show/NCT04470427?term=vaccine&cond=covid-19&draw=5

https://www.astrazeneca.com/media-centre/press-releases.html

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/astrazeneca-and-oxford-university-announce-landmark-agreement-for-covid-19-vaccine.html

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/covid-19-vaccine-azd1222-showed-robust-immune-responses-in-all-participants-in-phase-i-ii-trial.html

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/development-of-covid-19-vaccine-azd1222-expands-into-us-phase-iii-clinical-trial-across-all-adult-age-groups.html

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/statement-on-astrazeneca-oxford-sars-cov-2-vaccine-azd1222-covid-19-vaccine-trials-temporary-pause.html

https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-supply-canada-their-bnt162-mrna-based

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

https://www.who.int/news-room/q-a-detail/coronavirus-disease-(covid-19)-vaccines?adgroupsurvey={adgroupsurvey}&gclid=CjwKCAiAxKv_BRBdEiwAyd40N6EMObda_8apVcrFe7AtK4GTWbXVAtO3m8Gq02R_KoRdKc3T_wOJURoCzCAQAvD_BwE

https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/moderna-covid-19-vaccine

https://www.nbcnews.com/news/world/astrazeneca-s-covid-19-vaccine-approved-u-k-n1252418

About the Author:

Deborah Seah is a contributing writer for a column on PharmaSources.com, Discovering Biotechnology. The column explores innovative technologies in the world of biotech and evaluates its impact on our future. She is also an editor for a monthly science and technology magazine, Asia-Pacific Biotech News.
Prior to her career in writing she worked as a research associate at a plant genetics laboratory of a multinational agriculture company. Following that she also had experience in a medical diagnostics start-up as a medical technologist. "