Moderna Announces Publication in The New England Journal of Medicine of Interim Results From Phase 1 Study of Its mRNA Vaccine Against COVID-19 (mRNA-1273) - Business Wire

Interim analysis of original cohorts of Phase 1 study evaluated two-dose vaccination schedule of mRNA-1273 across three dose levels (25, 100, 250 µg) in 45 healthy adults ages 18-55 years; results reaffirm and expand upon positive interim data announced on May 18th.

Neutralizing antibody titers were observed in 100% of evaluated participants; at the 100 µg dose level selected for Phase 3, the geometric mean titers were above those seen in convalescent sera.

Vaccination with mRNA-1273 elicited Th1-biased CD4 T cell responses.

mRNA-1273 was generally safe and well-tolerated.

Data support 30,000 participant Phase 3 study expected to begin on July 27.

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Moderna, Inc., (Nasdaq:MRNA) a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, today announced the publication of an interim analysis of the open-label Phase 1 study of mRNA-1273, its vaccine candidate against COVID-19, in The New England Journal of Medicine.

This interim analysis evaluated a two-dose vaccination schedule of mRNA-1273 given 28 days apart across three dose levels (25, 100, 250 µg) in 45 healthy adult participants ages 18-55 years, and reports results through Day 57.

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 18th and show mRNA-1273 induced rapid and strong immune responses against SARS-CoV-2.

The study was led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

mRNA-1273 was generally safe and well-tolerated, with no serious adverse events reported through Day 57.

The most notable adverse events were seen at the 250 µg dose level, with three of those 14 participants (21%) reporting one or more severe events.

Solicited systemic adverse events were more common after the second vaccination and occurred in seven of 13 (54%) participants in the 25 µg group, all 15 participants in the 100 µg group and all 14 participants in the 250 µg group.

The most commonly reported systemic adverse events following second vaccination at the 100 µg dose were fatigue (80%), chills (80%), headache (60%) and myalgia (53%), all of which were transient and mild or moderate in severity.

The most common solicited local adverse event at the 100 µg dose was pain at the injection site (100%), which was also transient and mild or moderate in severity.

mRNA-1273 induced binding antibodies to the full-length SARS-CoV-2 Spike protein (S) in all participants after the first vaccination, with all participants seroconverting by Day 15.

Dose dependent increases in binding titers were seen across the three dose levels, and between prime and boost vaccinations within the dose cohorts.

Convalescent sera samples were tested using the same assays as the study samples.

No participants had detectable live SARS-CoV-2 virus neutralization or PsVNA responses prior to vaccination.

After two vaccinations, mRNA-1273 elicited robust neutralizing antibody titers.

At the Phase 3 selected dose of 100 µg, the geometric mean titer levels were 4.1-fold above those seen in reference convalescent sera (n=3).

After the second vaccination, PsVNA neutralizing antibody titers were detected in all participants in all dose cohorts.

The Day 57 geometric mean titers at the 100 µg dose were 2.1-fold higher than those seen in convalescent sera (n=38)3.

A clear dose response was seen in geometric mean titers between the 25 µg and 100 µg dose levels, with minimal additional increases at the 250 µg dose.

T-cell responses were also evaluated at the 25 µg and 100 µg dose levels.

Following second vaccination, mRNA-1273 elicited Th1-biased CD4 T-cell responses without significant elevation of Th2-biased CD4 T-cell responses.

Evaluation of the durability of immune responses is ongoing, and participants will be followed for one year after the second vaccination, with scheduled blood collections throughout that period.

An additional seven cohorts in this Phase 1 study have completed enrollment: a 50 µg cohort in adults 18-55 (n=15), three cohorts of older adults (n=30, ages 56-70, 25 µg, 50 µg, and 100 µg) and three cohorts of elderly adults (n=30, ages 71 and above, 25 µg, 50 µg, and 100 µg).

These data are expected to be published separately.

Given the increased morbidity and mortality of COVID-19 in older and elderly adults, additional evidence for the potential of a vaccine to protect this population is an urgent priority.

“These Phase 1 data demonstrate that vaccination with mRNA-1273 elicits a robust immune response across all dose levels and clearly support the choice of 100 µg in a prime and boost regimen as the optimal dose for the Phase 3 study,” said Tal Zaks, M.D., Ph.D., Chief Medical Officer of Moderna.

“We look forward to beginning our Phase 3 study of mRNA-1273 this month to demonstrate our vaccine’s ability to significantly reduce the risk of COVID-19 disease.”.

“These positive Phase 1 data are encouraging and represent an important step forward in the clinical development of mRNA-1273, our vaccine candidate against COVID-19, and we thank the NIH for their ongoing collaboration.

The Moderna team continues to focus on starting our Phase 3 study this month and, if successful, filing a BLA,” said Stéphane Bancel, Chief Executive Officer of Moderna.

“We are committed to advancing the clinical development of mRNA-1273 as quickly and safely as possible while investing to scale up manufacturing so that we can help address this global health emergency.”.

Both cohorts, healthy adults ages 18-55 years (n=300) and older adults ages 55 years and above (n=300), in the Company’s Phase 2 study of mRNA-1273 are 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.

The Phase 3 study protocol has been reviewed by the U.S.

Food and Drug Administration (FDA) and is aligned to 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 efficacy analysis will be an event-driven analysis based on the number of participants with symptomatic COVID-19 disease.

The target vaccine efficacy (VE) 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 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.

Registration for the COVE study is expected to be available at study centers across the country beginning on July 21 with study initiation on July 27.

Moderna is working closely with Operation Warp Speed (OWS) and the NIH, including NIAID’s COVID-19 Prevention Trials Network (COVPN), to conduct the Phase 3 COVE study.

Working together with collaborators like NIH, the Company hopes to achieve a shared goal that the participants in the COVE study are representative of the communities at highest risk for COVID-19 and of our diverse society.

Moderna has completed manufacture of vaccine required to start the Phase 3 study.

With the Phase 3 dose being finalized at 100 μg, the Company 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.

In addition, Moderna recently announced a collaboration with Catalent for large-scale, commercial fill-finish manufacturing of mRNA-1273 at Catalent’s biologics facility in Indiana.

On July 9, Moderna announced a collaboration with ROVI for large-scale, commercial fill-finish manufacturing of mRNA-1273 intended in principle to supply markets outside of the U.S.

Funding 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), partially supported the planning for the Phase 2 and Phase 3 studies of mRNA-1273 and is supporting the execution of these studies, as well as the manufacturing process scale-up of mRNA-1273.

Moderna will also fund costs required to complete the development of mRNA-1273 including portions of the Phase 3 study and the scale up of manufacturing capacity at the final established dosage in order to obtain licensure for mRNA-1273.

Data tables can be found at the bottom of this press release.

About mRNA-1273

mRNA-1273 is an mRNA vaccine against COVID-19 encoding for a prefusion stabilized form of the Spike (S) protein, which was selected by Moderna in collaboration with investigators from the VRC

The first participant in the NIAID-led Phase 1 study of mRNA-1273 was dosed on March 16, 63 days from sequence selection to Phase 1 study dosing

On May 12, the FDA granted mRNA-1273 Fast Track designation

Both cohorts, healthy adults ages 18-55 years (n=300) and older adults ages 55 years and above (n=300), in the Company’s Phase 2 study of mRNA-1273 are fully enrolled

More than 1,900 participants have been enrolled in Moderna’s infectious disease vaccine clinical studies under health authorities in the U.S., Europe and Australia

Clinical data demonstrate that Moderna’s proprietary vaccine technology has been generally well-tolerated and can elicit durable immune responses to viral antigens

Based on clinical experience across Phase 1 studies, the company designated prophylactic vaccines a core modality and is working to accelerate the development of its vaccine pipeline

The potential advantages of an mRNA approach to prophylactic vaccines include the ability to combine multiple mRNAs into a single vaccine, rapid discovery to respond to emerging pandemic threats and manufacturing agility derived from the platform nature of mRNA vaccine design and production

Moderna currently has nine development candidates in its prophylactic vaccines modality, including:

To date, Moderna has demonstrated positive Phase 1 data readouts for eight prophylactic vaccines (H10N8, H7N9, RSV, chikungunya virus, hMPV/PIV3, CMV, Zika and COVID-19)

Moderna’s CMV vaccine is currently in a Phase 2 dose-confirmation study

Moderna’s investigational Zika vaccine (mRNA-1893), currently in a Phase 1 study, was granted FDA Fast Track designation in August 2019

The company’s platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, providing Moderna the capability to pursue in parallel a robust pipeline of new development candidates

Headquartered in Cambridge, Mass., Moderna currently has strategic alliances for development programs with AstraZeneca PLC and Merck & Co., Inc., as well as the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S

Department of Defense, and 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

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including regarding the Company’s development of a potential vaccine against the novel coronavirus, the parameters of the Phase 1 and Phase 2 studies of mRNA-1273, the publication of study data for later cohorts in the Phase 1 study of mRNA-1273, the parameters and timing of the Phase 3 study of mRNA-1273, the potential filing of a biologics license application (BLA) for mRNA-1273, the Company’s potential manufacturing capabilities and projected vaccine dose production, and costs related to the mRNA-1273 program to be funded by the Company

These risks, uncertainties, and other factors include, among others: the fact that there has never been a commercial product utilizing mRNA technology approved for use; the fact that the rapid response technology in use by Moderna is still being developed and implemented; the fact that the safety and efficacy of mRNA-1273 has not yet been established; potential adverse impacts due to the global COVID-19 pandemic such as delays in regulatory review, manufacturing and clinical trials, supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy; and those other risks and uncertainties described under the heading “Risk Factors” in Moderna’s most recent Quarterly Report on Form 10-Q filed with the U.S

Data Tables

Moderna announces publication of interim results from Phase 1 study of its mRNA vaccine against COVID-19 (mRNA-1273) in NEJM