The Second Coronavirus Vaccine to Receive FDA Emergency Use Approval: Moderna mRNA-1273

Important Development: Moderna’s Vaccine Received FDA Emergency Use Authorization on December 20

As expected, the US Food and Drug Administration (FDA) granted emergency use authorization to Moderna’s coronavirus vaccine mRNA-1273. Thus, in the United States, a second vaccine made using the same technology (mRNA) as BioNTech and offering 95% protection has entered use. Moderna is beginning distribution of around 5 million vaccine doses in the first week. 

Moderna’s Vaccine Reports 94.5% Efficacy

On October 22, Moderna announced that enrollment in its phase-III COVE study was complete. According to results announced on November 16 from its study of 30 thousand people, the mRNA-1273 vaccine developed against coronavirus was 94.5 percent effective.

According to the analysis reported by the company, among participants receiving placebo, 90 developed illness caused by the novel coronavirus, namely COVID-19, whereas among volunteers receiving at least 2 doses of mRNA-1273, only 5 developed the disease.

The study’s second endpoint was severe COVID-19 infection. The vaccine was also reported to prevent severe coronavirus infection. Compared with 11 severe COVID-19 cases in the placebo group, among those receiving mRNA-1273 no severe COVID-19 was reported.

Moderna’s statement was as follows: "The vaccine developed was generally safe and well tolerated; adverse effects include muscle pain, headache and fatigue."

The phase-III COVE study has important strengths, including:

• 64% of participants were aged 45 or older, and 25% were aged 65 or older (showing that the vaccine is also effective in older people),
• 36% of participants had diabetes, 25% severe obesity, 19% significant cardiovascular disease and 18% chronic lung disease (showing effectiveness in people at high risk because of additional illnesses).

This protection rate looks better than the interim results announced last week for the BioNTech / Pfizer vaccine, which showed 90% protection.

How Does the mRNA-1273 Vaccine Work?

It all began with a person infected by the novel coronavirus in China...

The novel coronavirus’s genetic map was determined and uploaded to a public database. Scientists from the US National Institutes of Health and the biotechnology company Moderna worked together to identify the genetic code of a key protein on the virus, called the spike protein, and think it is a good vaccine candidate. Instructions for producing the spike protein are provided through a messenger RNA (mRNA) molecule, and mRNAs can be given directly to patients as a vaccine. This vaccine is injected in the same way as others. The mRNA reaches immune cells and instructs them to produce the spike protein. Our immune system then sees those cells as coronavirus cells. Immune cells examine these spike proteins and develop defenses against them. When someone encounters the actual coronavirus, the immune system is thus ready to protect them. How does this approach differ? Developing the vaccine does not require using the virus itself, which would take considerable time and involve many processes. Instead, we can use the information in the virus and transfer it directly to the patient. Ultimately, the patient develops their own vaccine. Using this approach, the US National Institutes of Health and Moderna managed to prepare a vaccine that went from genetic coding to testing in a record 42 days.

What Is the Price of Moderna’s Vaccine?

Moderna announced an anticipated retail price of 32-37 dollars for its mRNA-1273 vaccine. Under its BARDA agreement, it announced that it would sell the first 100 million doses to the United States for 25 dollars.

Moderna has so far announced agreements with the United States (100-400 million doses), Japan (50 million), Canada (20-36 million), Switzerland, Israel, Qatar and the European Union (80-160 million doses).

Moderna promises to produce 20 million doses by the end of 2020.

What Are the Storage and Transport Conditions for mRNA-1273? How Much Cold-chain Support Is Needed?

It can be stored at -20 degrees Celsius for up to 6 months. It can be kept in a refrigerator at 2 to -8 degrees for up to 30 days. After removal from refrigeration, it can be used at room temperature for up to 12 hours. It was announced that the vaccine would come in a ready-to-use syringe requiring no dilution.

Details of Moderna’s Potential Vaccine Study Against COVID-19

Moderna is one of the many groups seeking a solution to the COVID-19 Pandemic and is developing the mRNA-1273 vaccine candidate whose mechanism we described above. Its milestones are as follows;

Progress Up to November 16, 2020

• January 11: Chinese authorities shared the novel coronavirus’s genetic sequence.
• January 13: The US National Institutes of Health (NIH) and Moderna’s infectious disease research team finalized the sequence of the company’s novel coronavirus vaccine mRNA-1273. At that time, the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, announced its intention to use Moderna’s mRNA-1273 vaccine in a phase-I clinical trial.
• February 7: The first clinical batch, including vial filling and finishing, was completed in a total of 25 days from sequence selection to vaccine production. The batch then went for analytical testing.
• February 24: The first batch was shipped from Moderna to NIH for use in phase-I clinical trials.
• March 4: The US Food and Drug Administration (FDA) reviewed the application submitted by NIH for mRNA-1273 and allowed the clinical trials to begin.
• March 16: With the first participant dosed, the trial is expected to involve 45 healthy adult volunteers aged 18 to 55 over approximately six weeks.
• March 23: Moderna prepared an updated report, including information on the vaccine’s potential development path. The company reported that the phase-I study was progressing according to the protocol specified by NIAID. Although a marketable vaccine would take at least 12-18 months, it also reported possible emergency use in some people, probably including healthcare professionals, in the autumn. Any emergency use would require authorization from the relevant regulators. The company has also expanded its manufacturing capacity to produce millions of doses each month in individual or multidose vials. Capacity will increase depending on investment.
• March 27: NIH announced that healthy adult volunteers aged 18 to 55 would be enrolled at Emory University in Atlanta for the phase-I study of mRNA-1273.
• April 16: BARDA awarded Moderna up to 483 million dollars to accelerate development of mRNA-1273 for pandemic response and large-scale manufacturing in 2020.
• April 27: Moderna submitted an IND to the US FDA for a phase-II study of mRNA-1273.
• May 1: Moderna and Lonza announced a worldwide strategic collaboration to enable production of up to 1 billion doses of mRNA-1273 annually.
• May 12: Moderna received FDA Fast Track designation for mRNA-1273.
• May 18: Moderna announced positive interim phase-I data for mRNA-1273.
• May 29: The first participants in each age group were dosed in Moderna’s phase-II study of mRNA-1273.
• July 8: Moderna completed enrollment in its phase-II study of mRNA-1273.
• July 14: Interim results from the NIH-led phase-I trial were published in NEJM.
• July 26: BARDA expanded the agreement to support the larger phase-III programme for mRNA-1273.
• July 27: The phase-III study of mRNA-1273, conducted in collaboration with NIH and BARDA, began.
• August 11: Moderna announced a supply agreement with the US government for the first 100 million doses of mRNA-1273.
• September 8: Moderna signed a pledge to continue making vaccinated individuals’ safety and well-being the top priority in developing the first COVID-19 vaccines.
• September 29: Interim results from older age cohorts in the mRNA-1273 phase-I study (ages 56-70 and 71+) were published in NEJM.
• October 22: Moderna completed enrollment in its phase-III study of mRNA-1273.
• November 16: Moderna announced that its mRNA-1273 vaccine provided 94.5 percent protection against COVID-19.
• December 16: The FDA announced that it had granted Moderna’s vaccine "emergency use authorization."

Note: New treatments are tested in four stages (phases) for patient safety. Each stage is designed to answer different research questions. 

• Phase-I research involves a small number of people. Here, we try to find a safe dose, determine how and when the new medicine should be given, and establish how the new treatment affects the body. 
• Phase-II research determines the intervention’s effects on particular diseases (therapeutic or preventive).
• If a treatment shows potential benefits, it proceeds to phase-III research. This stage involves large numbers of patients, and researchers use them to compare new treatments directly with standard treatments, thereby developing new standards.
• Finally, phase-IV research aims to assess a treatment’s long-term safety and effectiveness further.

Information About the Technologies and Platforms Used by the Biotechnology Company Moderna

mRNA is an emerging platform. Over the past few years, Moderna has studied these vaccines in clinical trials involving more than 1000 participants. It has launched 9 clinical trials of mRNA vaccines in the last four years.

Its most advanced vaccine programmes (CMV) are in Phase 2 clinical testing, and it has no approved medicines to date.

The company previously collaborated within NIH on a vaccine for MERS-CoV, another coronavirus type.

The vaccine’s rapid production was enabled by the following: mRNA is an information molecule, and mRNA vaccines are designed using the viral sequence rather than by working on the virus itself. The mRNA platform therefore offers significant advantages.

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