Summary of findings from Phase 3 trial evaluating the Moderna COVID-19 vaccine is available here. Data from this study were analyzed by the US Food and Drug Administration (FDA) before it issued an emergency use authorization for this vaccine.
Studies in Children
- February 25, 2021: Moderna announced that it has completed enrollment of 3,000 adolescents aged 12-17 in a Phase 2/3 study evaluating the safety and efficacy of the mRNA-1273 vaccine in this age group. All participants have been recruited in the United States. This study is called the TeenCOVE study, after the original COVE study conducted in people age 18 and over. The company is planning to begin a third study (KidCOVE) focusing on children between the ages of 6 months and 11 years in the near future.
Development of Variant-Specific Vaccines
- February 24, 2021: Moderna announced that it has completed manufacture of a vaccine candidate tailored to protect against the B.1.351 variant of the SARS-CoV-2 virus first identified in the Republic of South Africa. The variant-specific vaccine is called mRNA-1273.351. The Company has shipped doses of the variant-specific vaccine to the National Institute of Allergy and Infectious Disease (NIAID) at the National Institutes of Health (NIH). NIAID will perform a small clinical trial (Phase 1) to determine if the mRNA-1273.351 vaccine boosts immunity against the South African variant. Moderna envisions offering the mRNA-1273.351 vaccine as a booster for people who have already received the original vaccine or making a multivalent vaccine that would include the original vaccine and the variant-specific vaccine in a single shot. This type of multivalent (or combined) vaccine strategy is currently used for vaccines to prevent many other conditions, including influenza.
Efficacy Against Different Strains of SARS-CoV-2
- January 26, 2021: Moderna announced results from a recently conducted in vitro study demonstrating that the Moderna vaccine, mRNA-1273, is likely to be effective in preventing infection from variant strains of the SARS-CoV-2 virus identified in the United Kingdom (called B.1.1.7) and South Africa (called B.1.351). Both of these variants of the SARS-CoV-2 virus have caused concern because they appear to be more contagious than the original virus. Although Moderna believes that the mRNA-1273 vaccine will provide protection against all variants of the SARS-CoV-2 virus identified to date, the recent study found that the mRNA-1273 vaccine, produces fewer neutralizing antibodies in response to the South African variant of the virus than in response to the original virus. This suggests than the vaccine may provide less protection against the South African variant of the virus. Therefore, the company has started to evaluate strategies to enhance vaccine efficacy. These include: determining if an additional booster dose of the mRNA-1273 vaccine increases the production of neutralizing antibodies against emerging virus strains including the B.1.351 variant and testing the efficacy of a modified vaccine (mRNA-1273.351) against the B.1.351 variant.
Timeline for FDA Application and Availability of Vaccine to the Public
- December 17, 2020: The US Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that an emergency use authorization (EUA) be issued for the Moderna candidate vaccine, mRNA-123. The committee voted on the following question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” The vote was 20-Yes, 0-No, and 1-Abstention. (Note: Although Moderna recently started enrolling children age 12-17 into the trial, data from these participants are not yet available. That is why the question was limited to individuals age 18 or older.) It is likely that the FDA will issue the EUA tomorrow. The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) is scheduled to meet on Saturday and Sunday of this week to vote on recommended uses of the Moderna COVID-19 vaccine under the EUA. The agenda for this meeting can be accessed here. The meeting will be live streamed and can be viewed here.
- December 15, 2020: The US Food and Drug Administration (FDA) has released detailed findings from the Phase 3 trial of the Moderna candidate vaccine, mRNA-1273. An 84-page document prepared by Moderna is available here and a 7-page addendum to this document is available here. A 54-page document prepared by the FDA is available here. On page 11 of this document the FDA states: “FDA has determined that the Sponsor has provided adequate information to ensure the vaccine’s quality and consistency for authorization of the product under an EUA” (Emergency Use Authorization). On page 12, the FDA states that the vaccine is proposed “for active immunization for the prevention of COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older.” We plan to report summarized safety and efficacy findings for the full sample and for different subgroups within the next few days.
- November 30, 2020: Moderna announced that it plans to submit a request to the US Food and Drug Administration (FDA) today for an Emergency Use Authorization (EUA) for its candidate vaccine, mRNA-1273. In their primary efficacy analyses, 196 cases of laboratory-confirmed symptomatic COVID-19 occurred. Of these 185 occurred among people who received the placebo vaccine and 11 occurred among those tho received the mRNA-1273 vaccine, resulting in an estimate of vaccine efficacy of 94.1%. Of the 196 cases of symptomatic COVID-19 that occurred, 30 were classified as SEVERE COVID-19, all of which occurred in the placebo group.
- November 11, 2020: Moderna reported that it has enough data for the first interim analysis from the Phase 3 trial of its experimental COVID-19 vaccine (mRNA-1273). It had submitted trial data to the independent board monitoring its trial, a sign that results could be announced shortly. The company said it expects this first interim analysis to include “substantially more than 53 cases,” which was the targeted trigger point for the analysis.
- November 11, 2020: Dr. Anthony Fauci predicted that Moderna could have data from the Phase 3 trial of its COVID-19 vaccine (mRNA-1273) anywhere between “a couple of days” to “a little more than a week”.
- October 22, 2020: According to a CNN report, Moderna’s president, Dr. Stephen Hoge, stated that “if all the stars align”, Moderna will apply for an emergency use authorization (EUA) for its COVID-19 vaccine (mRNA-1273) from the Food and Drug Administration (FDA) in early December 2020.
Milestones to Reach Before FDA Submission
53 study participants must develop laboratory-confirmed, symptomatic COVID-19.
At least 40 of these 53 people (75%) must be in the control group (that is, they received a placebo vaccine).
At least 15,000 study participants (50%) must be followed for at least 8 weeks after receiving their second dose of vaccine to assess possible side effects.
- September 30, 2020: Moderna CEO, Stéphane Bancel told the Financial Times that Moderna will not seek an emergency use authorization for its COVID-19 vaccine (mRNA-1273) from the Food and Drug Administration (FDA) before November 25, 2020.
- November 30, 2020: Moderna announced that it has completed the primary efficacy analysis for the Phase 3 study (known as the COVE study) testing its COVID-19 vaccine candidate, mRNA-1273.
- A total of 196 people in the study developed laboratory-confirmed, symptomatic COVID-19. Of these, 185 had received the placebo vaccine and 11 had received the mRNA-1273 vaccine. Thus, they estimated that the vaccine reduces the risk of getting symptomatic COVID-19 by 94.1%.
- In addition, a total of 30 people in the study developed severe COVID-19. All 30 had received the placebo vaccine.
- No serious safety concerns have been reported.
- Today, the Company will submit materials requesting a Emergency Use Authorization (EUA) for the mRNA-1273 vaccine from the United States (US) Food and Drug Administration (FDA). The Company expects these materials to be reviewed by the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on December 17, 2020.
- The Company expects to have about 20 million doses of the mRNA-1273 vaccine available in the United States by the end of 2020 and remains on track to manufacture 500 million to 1 billion doses globally in 2021.
- November 16, 2020: Moderna announced results of the first interim analyses for its COVID-19 vaccine candidate, mRNA-1273. They reported that the vaccine was 94.5% effective in preventing laboratory-confirmed, symptomatic COVID-19. This study is known as the COVE study. More than 30,000 participants in the US are enrolled in the study. About half of these participants received the mRNA-1273 vaccine and the other half received a placebo vaccine. 95 participants in the study developed laboratory-confirmed COVID-19. Of these, 90 had received the placebo vaccine and 5 had received the mRNA-1273 vaccine. Of the 95 people in the study who developed COVID-19, 11 had severe COVID-19. All of the people who developed severe COVID-19 had received the placebo vaccine. No significant safety concerns were reported. The most common “severe” side-effects were: fatigue (9.7%), muscle pain (8.9%), and joint pain (5.2%). A “severe” side effect was defined as one that prevented a participant from doing routine daily activities on at least one day following an injection.
- November 16, 2020: Moderna announced new data showing that its COVID-19 vaccine candidate, mRNA-1273, is more stable than originally estimated. The new data show that the vaccine remains stable:
- At standard freezer temperatures (-4º F) for 6 months,
- At standard refrigerator temperatures (36º to 46º F) for 30 days, and
- At room temperature for up to 12 hours.
This better than expected stability will make it easier to distribute the vaccine to sites where it can be administered. It will also make it easier for doctors, nurses and pharmacists to store and administer the vaccine. In addition, the greater stability will likely result is less waste. The vaccine will come in vials than contain 5 doses. Once a vial is removed from the freezer, health care providers will have 30 days to use all 5 doses.
- October 22, 2020: Moderna announced that all 30,000 study participants have been enrolled in the Phase 3 study of its COVID-19 investigational vaccine (mRNA-1273) and that 25,650 have received a second dose. (Note: The study protocol requires two doses of vaccine, given four weeks apart.)
7,000 of the 30,000 participants are age 65 or older
5,000 of the 30,000 participants are under age 65, but have chronic health problems that increase their risk of severe COVID-19
More than 6,000 of the 30,000 participants identify as Hispanic or LatinX
More than 3,000 of the 30,000 participants identify as Black or African-American
Around the World
- November 25, 2020: Moderna announced that it has reached a tentative agreement with the European Commission to provide 80 million doses of its vaccine candidate, mRNA-1273. The first doses would be delivered as early as the first quarter (January-March) of 2021. The agreement gives the European Commission the option of ordering up to 160 million doses. European Union Member States are reviewing the agreement before it is finalized. Moderna is working with manufacturing partners in Switzerland and Spain, to create a dedicated supply chain for the vaccine in countries outside of the United States. Globally, Moderna expects to be able to manufacture and deliver between 500 million to 1 billion doses of mRNA-1273 beginning in 2021.
- November 17, 2020: Moderna announced that it has reached an agreement with the United Kingdom (UK) to supply its COVID-19 vaccine candidate, mRNA-1273, beginning in March 2021, pending approval by the Medicines and Healthcare Products Regulatory Agency (MHRA, the UK equivalent of the Food and Drug Administration in the United States). The MHRA began the process of reviewing data from early trials of mRNA-1273 in late October 2020. The company is working with manufacturing partners in Switzerland and Spain, to create a dedicated supply chain for the vaccine in countries outside of the United States. Globally, Moderna expects to be able to manufacture and deliver between 500 million to 1 billion doses of mRNA-1273 beginning in 2021.
- November 16, 2020: The European Medicines Agency (EMA) announced that it had started a “rolling review” of data from studies involving Moderna’s vaccine candidate, mRNA1273. The EMA is the equivalent of the Food and Drug Administration in the United States. According to a previous EMA announcement, “A rolling review is one of the regulatory tools that EMA uses to speed up the assessment of a promising medicine or vaccine during a public health emergency. Normally, all data on a medicine’s effectiveness, safety and quality and all required documents must be submitted at the start of the evaluation in a formal application for marketing authorisation. In the case of a rolling review, EMA’s human medicines committee (CHMP) reviews data as they become available from ongoing studies, before a formal application is submitted. Once the CHMP decides that sufficient data are available, the formal application should be submitted by the company. By reviewing the data as they become available, the CHMP can reach its opinion sooner on whether or not the medicine or vaccine should be authorised.”
- October 8, 2020: Moderna announced it would not enforce patents related to its investigational COVID-19 vaccine (mRNA-1273) while the pandemic continues. This will allow other drug makers to use its vaccine technology.