As the coronavirus disease 2019 (COVID-19) pandemic continues to take a fearsome toll on human health, pharmaceutical companies, both old and new, raced to develop a safe and effective vaccine against the pathogen responsible, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Among the first to receive emergency use authorization by the US Food and Drug Administration (FDA) was the Moderna vaccine. Moderna is a pioneering firm in the area of messenger RNA (mRNA) therapeutics and vaccines. Using this platform, it has entered areas such as vaccines against infectious and cancer conditions, as well as delivery technology and manufacturing of therapeutics for chronic conditions.
The company plans to expand its production capacity to 3 billion doses in 2022. It already has supply contracts with many high-income countries and has already supplied millions of doses worldwide.
Timeline of the Moderna vaccine
The Moderna mRNA vaccine encodes a form of the SARS-CoV-2 spike that is stabilized in its pre-fusion conformation. This spike form was developed by scientists at Moderna collaborating with the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center.
The first batch of vaccine was prepared on February 7, 2020, and was analyzed before being shipped to the NIH on February 24. This marked less than 45 days from the selection of the spike sequence to a Phase 1 trial.
May 12, 2021, saw the vaccine change track to Vaccine Fast Track status, with the Phase 2 study beginning on May 29, 2020. This included adults above 18 years, in two age groups, split at age 55 years.
September 29 witnessed the publication of the second interim analysis of data from Phase 1 participants, aged 56-70 and 71+ years. By the end of November, Moderna filed for Emergency Use Authorization with the U.S.FDA, which was granted on December 18, 2020, for those aged 18 years or more.
A Conditional Marketing Authorization (CMA) application with the European Medicines Agency was also approved. It is now licensed for emergency use in the UK, Canada, Israel, the European Union, Singapore and Taiwan, among other countries. More are likely to follow as it is being reviewed in many other countries.
On April 30, 2021, Moderna reported that its mRNA vaccine had been added to the Emergency Use Listing (EUL) of the World Health Organization (WHO), as a tool to prevent COVID-19 in those aged 18 or over.
Booster vaccines against later variants
Moderna is also working on booster vaccines against COVID-19 that are specifically directed against the circulating viral variants that show partial or complete resistance to earlier antibodies. These include mRNA-1273.351, against the South African variant B.1351, and a multivalent mRNA-1273.211, which combines the original mRNA-1273 with mRNA-1273.351.
Preclinical trial data is available in preprint form on the bioRxiv* server, awaiting peer-review for publication. The Phase 2 trial is currently underway.
Importance of EUL
The EUL is an assessment aimed to examine new health products for safety, effectiveness and quality during a time of public health emergency to broaden their availability. The process makes use of both late-stage clinical trial data and independent assessments of the parameters mentioned above, carried out by WHO and independent examiners.
The current EUL followed a look at all the scientific data provided by the company, especially Phase 3 clinical study data. The analysis of this data was reported by the company on November 30, 2020, and emerging data will continue to be fed to the WHO. The delay by the manufacturer in providing the review data is responsible for the late date of EUL.
The WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) had already recommended its use in all adults in January 2021, with an estimated protective efficacy of 92% against symptomatic disease, beginning two weeks from the first dose.
The Moderna vaccine joins vaccines from Pfizer, which was the first to get EUL, Astra-Zeneca-SK Bio, Serum Institute of India, and Johnson and Johnson, while Sinopharm and Sinovac, from China, are under review.
The fact that the Moderna vaccine has been issued EUL will enable speedy regulatory approval for any country looking at the vaccine and thus accelerate its import and use. In addition, organizations such as UNICEF (United Nations Children’s Fund) can now buy the vaccine and distribute it to needy countries.
Moreover, the newly set up COVAX Facility, an UN-backed program to pool the buying and distribution of vaccines against COVID-19 for many low- and middle-income countries, requires an EUL from any vaccine supplier.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.