mRNA-1273 Vaccine Description
mRNA-1273 is an mRNA vaccine candidate against the novel coronavirus SARS-CoV-2 encoding for a prefusion stabilized form of the Spike (S) protein, which was selected by Moderna in collaboration with investigators at the NIAID Vaccine Research Center.
mRNA is an information molecule and Moderna, Inc. designs its mRNA vaccines using the sequence of the virus, not by working on the virus itself. The Moderna mRNA platform provides significant advantages in speed and efficiency, across basic science, manufacturing, and clinical development.
The S protein complex is necessary for membrane fusion and host cell infection and has been the target of vaccines against the coronaviruses responsible for Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS).
The first clinical batch, which was funded by the Coalition for Epidemic Preparedness Innovations, was completed on February 7, 2020, and underwent analytical testing; it was shipped to NIH on February 24th, 42 days from sequence selection.
The first participant in the NIH-led Phase 1 study of the mRNA-1273 vaccine was dosed on March 16, 2020, 63 days from sequence selection to Phase 1 study dosing. On August 26, 2020, Moderna presented data from the Phase I trial at the Advisory Committee on Immunization Practices meeting.
The new Phase 3 study (COVE) the protocol has been reviewed by the U.S. FDA and is aligned with recent guidance on clinical trial design for COVID-19 vaccine studies. The Phase 3 COVE study is being conducted in collaboration with the NIH and the Biomedical Advanced Research and Development Authority, which began on July 27, 2020, and enrollment of approximately 30,000 participants is on track to complete in September.
As of September 16, 2020, there were 25,296 participants enrolled in the COVE Phase 3 clinical study. And as of October 2, 2020, 19,369 participants have received their 2nd vaccination of Moderna's mRNA-1273 vaccine candidate.
On October 22, 2020, Moderna stated it will determine whether to submit a dossier to the U.S. FDA requesting Emergency Use Authorization based on an assessment of whether the potential benefit of the vaccine outweighs the potential risks, once the 2-months of median safety follow-up have accrued.
With the Phase 3 dose being finalized at 100 μg, the Company said it remains on track to be able to deliver approximately 500 million doses per year, and possibly up to 1 billion doses per year, beginning in 2021 from the Company’s internal U.S. manufacturing site and strategic collaboration with Lonza.
On November 16, 2020, Moderna announced 'the independent, NIH-appointed Data Safety Monitoring Board informed Moderna that the trial has met the statistical criteria pre-specified in the study protocol for efficacy, with a vaccine efficacy of 94.5%.'
Stéphane Bancel, Moderna's CEO stated in a press release: 'We look forward to the next milestones of submitting for a EUA in the U.S., and regulatory filings in countries around the world, while we continue to collect data on the safety and efficacy of the vaccine in the COVE study."
Moderna previously collaborated with the NIH on a vaccine for MERS-CoV, which is a different type of coronavirus than the current SARS-CoV-2 pandemic. This program was only at the research stage and was not tested in humans.
Funding from the Biomedical Advanced Research and Development Authority (BARDA) partially supported the planning for Phase 2 and Phase 3 studies of mRNA-1273 and is supporting the manufacturing process scale-up.
Moderna is advancing messenger RNA (mRNA) science to create a new class of transformative medicines for patients. mRNA medicines are designed to direct the body’s cells to produce intracellular, membrane, or secreted proteins that can have a therapeutic or preventive benefit and have the potential to address a broad spectrum of diseases. Headquartered in Cambridge, Mass., Moderna has been named a top biopharmaceutical employer. To learn more, visit www.modernatx.com.
mRNA-1273 Vaccine Distribution
In Europe, the Company stated it is working with its strategic manufacturing partners, Lonza of Switzerland and ROVI of Spain, for manufacturing and fill-finish outside of the UDA. This is a dedicated supply chain to support Europe and countries other than the USA that enter into purchase agreements with Moderna.
The distribution agreement with the US government signed on August 9, 2020, was disclosed on October 24, 2020.
And on October 26, 2020, Moderna announced a supply agreement with the Ministry of Public Health of Qatar for mRNA-1273, to support the Ministry’s ongoing efforts to secure early access to a safe and effective COVID-19 vaccine for the people of Qatar.
On October 29, 2020, Moderna, Inc. confirmed that the Ministry of Health, Labour, and Welfare of Japan and Takeda Pharmaceutical Co., Ltd. have agreed to purchase and distribute 50 million doses of mRNA-1273, subject to necessary regulatory approvals.
Additionally, on November 17, 2020, Moderna announced a supply agreement with the government of the United Kingdom to supply mRNA-1273, its COVID-19 vaccine candidate, beginning in March 2021 if it is approved for use by UK regulatory authorities.
Furthermore, on November 25, 2020, the company announced that the European Commission has approved an agreement to secure 80 million doses of mRNA-1273, as part of the European Commission’s goal to secure access to a safe and effective COVID-19 vaccine for Europe. Under the terms of the proposed agreement, the European Commission has the option to increase its purchase of mRNA-1273, from 80 million doses to a total of up to 160 million doses.
Moderna recently announced further progress towards ensuring the distribution, storage, and handling of the vaccine can be done using existing infrastructure.
mRNA-1273 Vaccine Dosage
Based on the results of the Phase 1 study, the data indicate that a 100 mcg dose of vaccine is generally well-tolerated across age strata, with solicited symptoms mostly mild-tomoderate in severity and self-limited duration; and Induces neutralizing Abs in the upper half of the range of convalescent serum across age strata, with the induction of Th-1 biased, CD4+ T-cells.
The 100 mcg dose will be evaluated in the Phase 3 study.
mRNA-1272 Vaccine Indication
Pediatric efficacy verification TBD.
mRNA-1273 Vaccine News
November 17, 2020 - Moderna, Inc., announced that the European Medicines Agency human medicines committee has started a rolling review of mRNA-1273, the Company’s vaccine candidate against COVID-19, following the confirmation of eligibility of mRNA-1273 for submission on October 14, 2020. Stéphane Bancel, Chief Executive Officer of Moderna added: “We will continue our ongoing dialogue with the EMA as we seek to develop a safe and effective vaccine. We are also scaling up global manufacturing with our strategic partners Lonza of Switzerland, and ROVI of Spain to be able to deliver approximately 500 million doses per year and possibly up to 1 billion doses per year, beginning in 2021.”
November 16, 2020 - Moderna, Inc. announced that the independent, NIH-appointed Data Safety Monitoring Board for the Phase 3 study of mRNA-1273, its vaccine candidate against COVID-19, has informed Moderna that the trial has met the statistical criteria pre-specified in the study protocol for efficacy, with a vaccine efficacy of 94.5%.
November 13, 2020 - The Swiss therapeutics products agency Swissmedic has started a review of the anti-Covid 19 vaccine from Moderna in the rolling submission procedure. “The rolling submission procedure for mRNA-1273 is based on the initially submitted data packages on the preclinical situation and quality, as well as on preliminary clinical data. In a rolling review, the data can be evaluated as soon as they become available. The companies can then submit the latest data continuously without having to wait for the conclusive results from all studies."
October 29, 2020 - Stéphane Bancel, Moderna’s Chief Executive Officer, stated: “We look forward to our expected first review of our interim efficacy data, which is expected in November.”
October 29, 2020 - Moderna announced it has received $1.1 billion of customer deposits for the future supply of the mRNA-1273 vaccine candidate in Q3 2020, recorded as deferred revenue.
October 27, 2020 - Moderna announced that the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom has started the rolling review process of mRNA-1273. This rolling review process allows the MHRA to begin its independent assessment using the information submitted by Moderna and accept new evidence as it becomes available until the application is deemed complete. This process can reduce time to authorization while maintaining usual high standards of safety, efficacy, and quality.
October 22, 2020 - Moderna, Inc. announced that it has completed enrollment of 30,000 participants for the Phase 3 COVE study of mRNA-1273, its vaccine candidate against COVID-19, being conducted in collaboration with the National Institute of Allergy and Infectious Diseases. To date, more than 25,650 participants have received their second vaccination.
October 15, 2020 - A NEJM article was published: Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.
October 14, 2020 - Moderna, Inc. announced that it has received written confirmation from the European Medicines Agency (EMA) that mRNA-1273 is eligible for submission of an application for a European Union Marketing Authorization under the Agency’s centralized procedure. Confirmation of eligibility was given in response to the submission of a letter of intent enabling Moderna to evaluate the opportunity for submitting a Marketing Authorization Application for mRNA-1273 with the EMA.
October 13, 2020 - U.S. NIH's Director's Blog: COVID-19 Vaccine Appears Well-Tolerated and Effective in Developing Antibodies in Small Study of Older Adults.
October 13, 2020 - Moderna announced the initiation of a rolling submission to Health Canada for mRNA-1273, the Company’s vaccine candidate against COVID-19. This initiation follows positive results from a preclinical viral challenge study of mRNA-1273 and the positive interim analysis of the Phase 1 study of mRNA-1273 published in the New England Journal of Medicine.
October 2, 2020 - Moderna Inc. says the COVE Phase 3 Study enrolled 28,043 participants and 19,369 participants have received their second vaccination.
September 29, 2020 - Moderna, Inc. announced the publication of the second interim analysis of the open-label Phase 1 study of mRNA-1273, its vaccine candidate against COVID-19, in The NEJM. This interim analysis found that both the 25 µg and 100 µg dose levels were generally well-tolerated in both age cohorts. Immune responses were dose-dependent with the 100 µg dose eliciting higher binding and neutralizing antibody titers, supporting the selection of the 100 µg dose for further study in the Phase 3 trial.
September 17, 2020 - Moderna reported COVID vaccine candidate (mRNA-1273) Phase 3 COVE study has enrolled 25,296 participants and 10,025 participants have received their 2nd vaccination to date.
August 28, 2020 - Moderna, Inc. confirmed that the Company is engaged in discussions with the Ministry of Health, Labour, and Welfare of Japan (MHLW) to potentially purchase 40 million or more doses of the mRNA-1273 vaccine candidate. Under the terms of this arrangement, the vaccine would be supplied by Moderna, Inc. and distributed in Japan by Takeda Pharmaceutical Co., Ltd. beginning in the first half of 2021, if the vaccine receives regulatory approval.
August 26, 2020 - Moderna presented data from the Phase I trial of its mRNA-1273 vaccine candidate at the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
August 24, 2020 - Moderna announced that the Company has concluded advanced exploratory talks with the European Commission (EC) to supply 80 million doses of mRNA-1273, Moderna’s vaccine candidate against COVID-19 disease. The potential purchase agreement provides an option for the EC Member States to purchase an additional 80 million doses for a total of up to 160 million doses.
August 11, 2020 - Moderna announced that the U.S. government has secured 100 million doses of mRNA-1273 as part of the U.S. government’s goal of securing early access to safe and effective COVID-19 vaccines for the American people. This award of up to $1.525 billion is for the manufacturing and delivery of 100 million doses of mRNA-1273 including incentive payments for timely delivery of the product.
July 28, 2020 - NEJM study: Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.
July 26, 2020 - Moderna, Inc. announced a modification to its contract with the Biomedical Advanced Research and Development Authority for an additional commitment of up to $472 million to support late-stage clinical development including the expanded Phase 3 study of the Company’s mRNA vaccine candidate mRNA-1273.
July 14, 2020 - Moderna, Inc. announced the publication of an interim analysis of the open-label Phase 1 study of its mRNA-1273 vaccine candidate in The New England Journal of Medicine. This interim analysis evaluated a two-dose vaccination schedule. Results from participants in the initial dose cohorts who received both vaccinations and were evaluated at pre-specified timepoints reaffirm the positive interim data assessment announced on May 18, 2020, and show mRNA-1273 induced rapid and strong immune responses against SARS-CoV-2.
July 14, 2020 - A Preliminary Report published by the NEJM found the mRNA-1273 vaccine-induced anti–SARS-CoV-2 immune responses in all participants and no trial-limiting safety concerns were identified. These findings support further development of this vaccine.
July 9, 2020 - Moderna, Inc. announced a collaboration for large-scale, commercial fill-finish manufacturing of Moderna’s mRNA vaccine candidate against COVID-19 (mRNA-1273) at ROVI’s facility in Madrid, Spain.
July 8, 2020 - Moderna, Inc. announced that it has completed enrollment for both cohorts of the Phase 2 study of its coronavirus vaccine candidate, mRNA-1273. And, Moderna has finalized the Phase 3 study protocol based on feedback from the U.S. Food and Drug Administration.
July 1, 2020 - Inside Moderna: The COVID Vaccine Front-Runner With No Track Record and an Unsparing CEO.
June 25, 2020 - Moderna and Catalent, Inc. announced a collaboration for large-scale, commercial fill-finish manufacturing of Moderna’s mRNA-based COVID-19 vaccine candidate (mRNA-1273) at Catalent’s biologics facility in Indiana. As part of the agreement, Catalent will provide manufacturing operations at the site to support the production of an initial 100 million doses of the vaccine candidate intended to supply the U.S. market starting in the third quarter of 2020.
June 17, 2020 - Reuters reported Israel has signed an agreement with Moderna for the future purchase of its potential COVID-19 vaccine.
June 11, 2020 - A non-peer-reviewed study of Moderna Inc.'s COVID-19 vaccine candidate in mice lends some assurance that it will not increase the risk of more severe disease and that 1-dose may provide protection against the novel coronavirus. This study showed that mRNA-1273 vaccination induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in the lungs and noses of mice without evidence of immunopathology.
June 11, 2020 - Moderna announced progress on the late-stage development of mRNA-1273, the Company’s mRNA vaccine candidate against COVID-19. Moderna has finalized the Phase 3 study protocol based on feedback from the U.S. FDA. The randomized, 1:1 placebo-controlled trial is expected to include approximately 30,000 participants enrolled in the U.S. and is expected to be conducted in collaboration with the National Institute of Allergy and Infectious Diseases.
June 2, 2020 - Moderna, Inc. announced new research to be highlighted at the Company’s third annual Science Day. The program is designed to provide insight into the continued diverse efforts underway at Moderna and with collaborators to better understand how to use mRNA as medicine and underscores the Company’s continued commitment to basic science and innovation.
May 29, 2020 - Moderna, Inc. announced that the first participants in each age cohort have been dosed in the Company’s Phase 2 study of its mRNA vaccine candidate (mRNA-1273) against the novel coronavirus SARS-CoV-2.
May 18, 2020 - Moderna announced positive interim clinical data of mRNA-1273, its vaccine candidate against novel coronavirus (SARS-CoV-2), from the Phase 1 study led by the NIAID. “These interim Phase 1 data, while early, demonstrate that vaccination with mRNA-1273 elicits an immune response of the magnitude caused by natural infection starting with a dose as low as 25 µg,” said Tal Zaks, M.D., Ph.D., Chief Medical Officer.
May 12, 2020 - Moderna, Inc. announced that the U.S. FDA has granted Fast Track designation for the Company’s mRNA vaccine candidate (mRNA-1273) against the novel coronavirus (SARS-CoV-2). Previously, on May 6th, the FDA said it completed the review of the Investigational New Drug (IND) application for mRNA-1273 allowing it to proceed to a Phase 2 study, which is expected to begin shortly. And, Moderna said it is finalizing the protocol for a Phase 3 study, expected to begin in the early summer of 2020.
May 8, 2020 - 'If Moderna’s coronavirus vaccine proves to work, the company anticipates working “very closely” with the U.S. government to determine 'who' will get the first mRNA-1273 doses, CEO Stephane Bancel told CNBC.
May 7, 2020 - Stéphane Bancel, Moderna’s Chief Executive Officer, said in a press statement, “The imminent Phase 2 study start is a crucial step forward as we continue to advance the clinical development of mRNA-1273, our vaccine candidate against SARS-CoV-2. With the goal of starting the mRNA-1273 pivotal Phase 3 study early this summer, Moderna is now preparing to potentially have its first Biologics License Application approved as soon as 2021."
May 1, 2020 - Moderna, Inc. and Lonza Ltd. today announced a 10-year strategic collaboration agreement to enable larger-scale manufacture of Moderna’s mRNA vaccine (mRNA-1273) against the novel coronavirus (SARS-CoV-2) and additional Moderna products in the future.
April 27, 2020 - Moderna, Inc. announced that it has submitted an IND application to the U.S. FDA for the company’s mRNA vaccine candidate (mRNA-1273) against the SARS-CoV-2 coronavirus to evaluate mRNA-1273 in Phase 2 and late-stage studies if supported by safety data from the Phase 1 study led by the National Institute of Allergy and Infectious Diseases.
April 23, 2020 - The USA Today reports the Seattle volunteers who got shots in the first trial of a possible coronavirus vaccine are now getting the second shot — an indicator the early trial is progressing well. The doctors at Kaiser Permanente's Vaccine Treatment and Evaluation Unit in Seattle don’t know the results of the first round of tests, said Lisa Jackson, who is leading the study.
April 16, 2020 - Moderna, Inc. announced an agreement for a commitment of up to $483 million from the Biomedical Advanced Research and Development Authority (BARDA), a division of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), to accelerate the development of the Company’s mRNA vaccine candidate (mRNA-1273) against the novel coronavirus SARS-CoV-2.
March 27, 2020 - The NIH announced that Emory University in Atlanta will begin enrolling healthy adult volunteers ages 18 to 55 years in the NIH-led Phase 1 study of mRNA-1273.
March 16, 2020 - Moderna, Inc. announced that the first participant has been dosed in the Phase 1 study of the Company’s mRNA vaccine (mRNA-1273) against the novel coronavirus (SARS-CoV-2). This Phase 1 study is being conducted by the National Institutes of Health under its own Investigational New Drug application.
February 24, 2020 - Moderna, Inc. announced that it has released the first batch of mRNA-1273, the Company’s vaccine against the novel coronavirus, for human use. Vials of mRNA-1273 have been shipped to the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health to be used in the planned Phase 1 study in the U.S.
January 23, 2020 - Moderna, Inc. announced a new collaboration to develop an mRNA vaccine against the novel coronavirus SARS-CoV-2.
January 13, 2020 - 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. The manufacture of this batch was funded by the Coalition for Epidemic Preparedness Innovations (CEPI).
mRNA-1273 Vaccine Definition
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.
mRNA is a single-stranded molecule that carries genetic code from DNA in a cell’s nucleus to ribosomes, the cell’s protein-making machinery. mRNA medicine instructs a patient’s own cells to produce proteins that could prevent, treat, or cure disease.
The mRNA sequence to the cells responsible for making the protein via one of several modalities. Reaching different types of cells requires different delivery methods.
mRNA-1273 Vaccine Clinical Trial
- NCT04283461 Phase 1 - This is a phase I, open-label, dose-ranging clinical trial in males and non-pregnant females, starting at 18 years of age, inclusive, who are in good health and meet all eligibility criteria. This clinical trial is designed to assess the safety, reactogenicity, and immunogenicity of mRNA-1273 manufactured by ModernaTX, Inc. mRNA-1273 is a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine that encodes for a full-length, prefusion stabilized spike (S) protein of SARS-CoV-2. Enrollment will occur at up to 3 domestic clinical research sites. One hundred and fifty-five subjects will be enrolled into one of thirteen cohorts (10 micrograms [mcg], 25 mcg, 50 mcg, 100 mcg, and 250 mcg). Subjects will receive an intramuscular (IM) injection (0.5 milliliters [mL]) of mRNA-1273 on Days 1 and 29 in the deltoid muscle and will be followed through 12 months post-second vaccination (Day 394).
- Follow-up visits will occur 1, 2, and 4 weeks post each vaccination (Days 8, 15, 29, 36, 43, and 57), as well as 3, 6, and 12 months post-second vaccination (Days 119, 209, and 394). The primary objective is to evaluate the safety and reactogenicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart, across 5 dosages in healthy adults.
- NCT04405076 Phase 2 - The first cohort of healthy adults ages 18-54 years (n=300) in the Phase 2 study of mRNA-1273 is fully enrolled, 13 days after the first participant was dosed. The sentinel participants in the cohort of older adults ages 55 years and above (n=50) is fully enrolled. This Phase 2 study, being conducted by Moderna, is evaluating the safety, reactogenicity, and immunogenicity of two vaccinations of mRNA-1273 given 28 days apart.
- The Company intends to enroll 600 healthy participants across two cohorts of adults ages 18-54 years (n=300) and older adults ages 55 years and above (n=300). Each participant will be assigned to receive a placebo, a 50 μg, or a 100 μg dose at both vaccinations. Participants will be followed through 12 months after the second vaccination.
NCT04470427 Phase 3 - The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of mRNA-1273 to prevent COVID-19 for up to 2-years after the second dose of mRNA-1273. Last updated on September 28, 2020.
- The Phase 3 study protocol has been reviewed by the U.S. Food and Drug Administration (FDA) and is aligned with recent FDA guidance on clinical trial design for COVID-19 vaccine studies. 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. The primary endpoint will be the prevention of symptomatic COVID-19 disease. Key secondary endpoints include the prevention of severe COVID-19 disease and the prevention of infection by SARS-CoV-2.
- The primary efficacy analysis will be an event-driven analysis based on the number of participants with symptomatic COVID-19 disease. The target vaccine efficacy against COVID-19 for powering assumptions is 60% (95% confidence interval to exclude a lower bound >30%). Data will be reviewed by an independent Data Safety Monitoring Board organized by NIH. The trial is expected to have two interim analyses (at approximately 53 and 106 events), prior to a final event-driven analysis, at approximately 151 events. The primary efficacy analysis will be an event-driven analysis based on the number of participants with symptomatic COVID-19 disease.
- This Phase 3 study has been named the COVE study.