Medicine PharmaceuticalsCOVID-19 vaccine
Moderna is proud to be among the many groups working to respond to this continuing global health emergency.
The Moderna COVID‑19 Vaccine has not been approved or licensed by the US Food and Drug Administration (FDA), but has been authorized for emergency use by FDA, under an Emergency Use Authorization (EUA), to prevent Coronavirus Disease 2019 (COVID‑19) for use in individuals 18 years of age and older. There is no FDA-approved vaccine to prevent COVID‑19.
The EUA for the Moderna COVID‑19 Vaccine is in effect for the duration of the COVID‑19 EUA declaration justifying emergency use of the vaccine, unless terminated or revoked (after which the vaccine may no longer be used).
Messenger RNA, or mRNA, plays a fundamental role in human biology, transferring the instructions stored in DNA to make the proteins required in every living cell. Our approach is to use mRNA medicines to instruct a patient’s own cells to produce proteins that could prevent, treat, or cure disease. The Moderna COVID‑19 Vaccine uses mRNA to provide a blueprint for your cells to build your body’s defense against SARS‑CoV‑2, the virus that causes COVID‑19. The Moderna COVID‑19 Vaccine does not contain SARS‑CoV‑2, or any virus—just the blueprint to help fight against it. The Moderna COVID‑19 Vaccine may not protect everyone.
On January, 2020, the Chinese authorities shared the genetic sequence of the novel coronavirus. the U.S. National Institutes of Health (NIH) and Moderna’s infectious disease research team finalized the sequence for mRNA-1273, the Company’s vaccine against the novel coronavirus. At that time, the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, disclosed their intent to run a Phase 1 study using the mRNA-1273 vaccine in response to the coronavirus threat and Moderna mobilized toward clinical manufacture. Manufacture of this batch was funded by the Coalition for Epidemic Preparedness Innovations (CEPI).
On February 2020, the first clinical batch, including fill and finishing of vials, was completed, a total of 25 days from sequence selection to vaccine manufacture. The batch then proceeded to analytical testing for release.the clinical batch was shipped from Moderna to the NIH for use in their Phase 1 clinical study.
On March 2020, the U.S. Food and Drug Administration (FDA) completed its review of the Investigational New Drug (IND) application filed by the NIH for mRNA-1273 and allowed to the study to proceed to begin clinical trials. the NIH announced that the first participant in its Phase 1 study for mRNA-1273 was dosed, a total of 63 days from sequence selection to first human dosing.
This Phase 1 study will provide important data on the safety and immunogenicity of mRNA-1273. Immunogenicity means the ability of the vaccine to induce an immune response in participants. The open-label trial is expected to enroll 45 healthy adult volunteers ages 18 to 55 years over approximately six weeks.
mRNA is an emerging platform. Over the past few years, we have demonstrated its potential in vaccines across more than 1,000 subjects in our clinical trials. This includes successful early-stage (Phase 1) clinical trials against five other respiratory viruses (two pandemic influenza strains, RSV, hMPV, and PIV3). Over the last four years, we have started 9 clinical trials for mRNA vaccines.
mRNA is an information molecule and we design our mRNA vaccines using the sequence of the virus, not by working on the virus itself. Our mRNA platform provides significant advantages in speed and efficiency, across basic science, manufacturing, and clinical development.
Moderna currently has 9 development candidates in its prophylactic vaccines modality. To date, Moderna has demonstrated positive Phase 1 data readouts for 6 prophylactic vaccines (H10N8, H7N9, RSV, chikungunya virus, hMPV/PIV3 and CMV).
For mRNA-1273, we were able to leverage our experience in vaccines to move rapidly on design and manufacture of material for the Phase 1 clinical trial. This included our broad understanding of the safety of our platform to date across more than 1,000 subjects. We also benefited from the use of our well-established manufacturing capabilities, which produced over 100 batches of mRNA medicines for use in human clinical trials in just the last two years.
The Company is actively preparing for a potential Phase 2 study under its own Investigational New Drug (IND) filing to build on data from the ongoing Phase 1 study being conducted by the NIH. To continue to progress this potential vaccine during the ongoing global public health emergency, Moderna intends to work with the FDA and other government and non-government organizations to be ready for a Phase 2 and any subsequent trials, which are anticipated to include a larger number of subjects and which will seek to generate additional safety and immunogenicity data. Manufacture of the mRNA-1273 material for the potential Phase 2 trial, which could begin in a few months, is underway. Moderna continues to prepare for rapid acceleration of its manufacturing capabilities that could allow for the future manufacture of millions of doses should mRNA-1273 prove to be safe and effective.
On June 11, 13 days 2020 after the first participant was dosed, the Company announced that the cohort of healthy younger adults ages 18-55 (n=300) and the sentinel group of older adults ages 55 years and above (n=50) in the Phase 2 study of mRNA-1273 was complete. After reviewing the safety data from the sentinel cohort of older adults, on June 25, the Data and Safety Monitoring Committee of the study recommended Moderna to proceed with enrollment for the remainder of the Phase 2 study. The cohort of older adults (n=300) has now been fully enrolled. This Phase 2 placebo-controlled, dose-confirmation study is evaluating the safety, reactogenicity and immunogenicity of two vaccinations of mRNA-1273 given 28 days apart. Each participant is receiving placebo, a 50 μg or a 100 μg dose at both vaccinations. Moderna has finalized the Phase 3 study protocol based on feedback from the U.S. Food and Drug Administration (FDA). The randomized, 1:1 placebo-controlled trial is expected to include approximately 30,000 participants at the 100 µg dose level in the U.S. and is expected to be conducted in collaboration with NIAID, subject to regulatory approval. Moderna has completed manufacture of vaccine required to start the Phase 3 study. A Phase 3 randomized, placebo-controlled, observer-blind clinical trial to evaluate the efficacy, safety, and immunogenicity of the Moderna COVID‑19 Vaccine in participants 18 years of age and older is ongoing in the United States (NCT04470427).
Randomization was stratified by age and health risk: 18 to <65 years of age without comorbidities (not at risk for progression to severe COVID‑19), 18 to <65 years of age with comorbidities (at risk for progression to severe COVID‑19), and 65 years of age and older with or without comorbidities.
The primary efficacy analysis population (referred to as the Per-Protocol Set), included 28,207 participants who received two doses (at 0 and 1 month) of either Moderna COVID‑19 Vaccine (n=14,134) or placebo (n=14,073), and had a negative baseline SARS‑CoV‑2 status.
The median length of follow up for efficacy for participants in the study was 9 weeks post Dose 2. There were 11 COVID‑19 cases in the Moderna COVID‑19 Vaccine group and 185 cases in the placebo group, with a vaccine efficacy of 94.1% (95% confidence interval of 89.3% to 96.8%). Cases of COVID‑19, starting 14 days after Dose 2, were defined as symptomatic COVID‑19 requiring positive RT-PCR result and at least two systemic symptoms or one respiratory symptom. Among all participants in the Per-Protocol Set analysis, which included COVID‑19 cases confirmed by an adjudication committee, no cases of severe COVID‑19 were reported in the Moderna COVID‑19 Vaccine group compared with 30 cases reported in the placebo group (incidence rate 9.138 per 1,000 person-years). One PCR-positive case of severe COVID‑19 in a vaccine recipient was awaiting adjudication at the time of the analysis.
Side effects that have been reported with the Moderna COVID‑19 Vaccine include:
Injection site reactions: pain, tenderness and swelling of the lymph nodes in the same arm of the injection, swelling (hardness), and redness
General side effects: fatigue, headache, muscle pain, joint pain, chills, nausea and vomiting, and fever
There is a remote chance that the Moderna COVID‑19 Vaccine could cause a severe allergic reaction. A severe allergic reaction would usually occur within a few minutes to one hour after getting a dose of the Moderna COVID‑19 Vaccine. For this reason, your vaccination provider may ask you to stay at the place where you received your vaccine for monitoring after vaccination. Signs of a severe allergic reaction can include:
Swelling of your face and throat
A fast heartbeat
A bad rash all over your body
Dizziness and weakness
These may not be all the possible side effects of the Moderna COVID‑19 Vaccine. Serious and unexpected side effects may occur. The Moderna COVID‑19 Vaccine is still being studied in clinical trials.