Moderna Inc. (Nasdaq: MRNA), the biotechnology company with one of the authorized vaccines for COVID-19, completed the manufacturing of clinical trial material for its variant-specific vaccine candidate, mRNA-1273.351, against the SARS-CoV-2 variant known as B.1.351 first identified in the Republic of South Africa, and has shipped doses to the National Institutes of Health (NIH) for a Phase 1 clinical trial that will be led and funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The Company also is providing an update on its strategy for addressing SARS-CoV-2 variants of concern. To ensure a cautious approach, the company pursues two strategies targeting the variants subject to review by the U.S. Food and Drug Administration (FDA). This includes 1) evaluating booster doses of vaccine to increase neutralizing immunity against the variants of concern and 2) evaluate mRNA-1273.351 and mRNA-1273.211 as a primary vaccination series for those who are seronegative. These candidates will be evaluated in a two-dose series at the 100 µg dose level and lower. Based on demand for the vaccine during pandemic conditions, the company forecasts over $18 billion in revenue this year, putting the Massachusetts-based venture on the path to profitability for the first time since its inception in 2010.
As the U.S. FDA recently updated the FDA Guidance for Industry, the company will investigate immunogenicity and safety in participants who have yet to receive a COVID-19 vaccine, as well as participants in clinical studies who previously received the mRNA-1273 vaccine.
TrialSite follows up here with a brief breakdown of the Moderna vaccine updated information as well as other news about the company.
First, the Moderna COVID-19 vaccine is authorized under emergency use authority in the U.S. by the FDA. Is this a different classification than fully registered or approved?
Yes. The EUA process is not the same as an FDA approval or clearance. Under an EUA, as reported by the FDA, the FDA makes the product available to the public, based on the best available evidence, without the need to wait for all of the usual evidence necessary for a full approval or clearance. In making these decisions, the FDA must balance and carefully assess the products’ risks and benefits based on currently available data.
EUAs are effective until the emergency declaration ceases. Additionally, an EUA can be revised or revoked by the FDA at any time as the agency continues to evaluate incoming data. The FDA offers a video for the public to learn more about the distinctions here.
For their first strategy, which involves the evaluation of booster doses of vaccine to boost neutralizing immunity against the variants, what are the three approaches they are taking?
The company plans to investigate three options including 1) a variant-specific booster candidate, mRNA-1273.351, based on the B.1.351 variant first identified in the Republic of South Africa at the 50 µg dose level and lower; 2) a multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273, their authorized vaccine against ancestral strains, and mRNA 1273.351 in a single vaccine at the 50 µg dose level and lower and 3) a third dose of mRNA-1273, the Moderna COVID-19 Vaccine, as a booster at the 50 µg dose level. The company reports it has already commenced dosing this cohort with the booster.
What is this NIAID-sponsored clinical trial about?
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute of Health (NIH) will conduct a Phase 1 clinical trial to investigate if mRNA-1273.351 can boost immunity against the variants of concern. The company will supply the doses of mRNA-1273.351 to the NIH.
NIAID plans on conducting this study once it receives a safe-to-proceed authorization from the FDA. NIAID will provide additional information when the trial begins, including disclosure on the public website clinicaltrials.gov. TrialSite will keep an eye out for more material information.
Will the company also conduct its own clinical trials to support regulatory filings for any booster vaccine or updated primary vaccine?
What does the current vaccine protocol call for?
The current Moderna COVID-19 Vaccine protocol calls for two 100 µg doses.
What is Moderna’s main goal here based on the unfolding situation?
As their CEO Stéphane Bancel recently stated, they are first and foremost grateful for the ongoing support collaboration with NIAID affords the biotech firm. Second, their intellectual property, based on the flexibility of the mRNA-based platform, supports the agile movement in research to test new iterations to the investigational product in an effort to counter the emerging variants of the virus.
In their latest press release, the CEO shared that the company is committed to ongoing updates to their investigational product till the pandemic is under control. The hope here is that the booster dose can be done at lower dose levels enabling more dose availability to the global community by late 2021 to 2022 as needed.
Moderna recently addressed the evolving situation in a letter to the editor of the New England Journal of Medicine on February 17, 2021—what were their main points?
The vaccination with the Moderna COVID-19 Vaccine produced neutralizing titers against all key emerging variants tested, including B.1.1.7 and B.1.351, first identified in the UK and Republic of South Africa, respectively. The study showed no significant impact on neutralizing titers against the B.1.1.7 variant relative to prior variants. A six-fold reduction in neutralizing titers was observed with the B.1.35 variant relative to prior variants.
How much funding has Moderna received thus far from government sources?
The Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services (HHS), is supporting the continued research and development of mRNA-1273 with $955 million in federal funding under contract no. 75A50120C00034. BARDA is reimbursing Moderna for 100 percent of the allowable costs incurred by the Company for conducting the program described in the BARDA contract. The U.S. government has agreed to purchase a supply of mRNA-1273 under U.S Department of Defense contract no. W911QY-20-C-0100.
Note that the Coalition for Epidemic Preparedness Innovations funded the first clinical batch of the vaccine product in February 2020.
What has been the clinical history of the vaccine product thus far?
The Moderna vaccine product developed initially alongside investigators from the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center led to a first batch thanks to funding from the Coalition for Epidemic Preparedness Innovations. The first experimental vaccine product was completed on February 7, 2020, and underwent analytical testing; it was shipped to the National Institutes of Health (NIH) on February 24, 2020, 42 days from sequence selection.
The first participant in the NIAID-led Phase 1 study of the Moderna COVID-19 Vaccine was dosed on March 16, 2020, 63 days from sequence selection to Phase 1 study dosing. On May 12, 2020, the U.S Food and Drug Administration granted the Moderna COVID-19 Vaccine Fast Track designation. On May 29, 2020, the first participants in each age cohort: adults ages 18-55 years (n=300) and older adults ages 55 years and above (n=300), were dosed in the Phase 2 study of the vaccine. On July 8, 2020, the Phase 2 study completed enrollment.
Results from the second interim analysis of the NIH-led Phase 1 study of the Moderna COVID-19 Vaccine in the 56-70 and 71+ age groups were published on September 29, 2020, in The New England Journal of Medicine.
On July 28, 2020, results from a non-human primate preclinical viral challenge study evaluating the vaccine were published in The New England Journal of Medicine. On July 14, 2020, an interim analysis of the original cohorts in the NIH-led Phase 1 study of the vaccine was published in The New England Journal of Medicine. On November 30, 2020, Moderna announced the primary efficacy analysis of the Phase 3 study of the vaccine conducted on 196 cases.
On December 3, 2020, a letter to the editor was published in The New England Journal of Medicine, reporting that participants in the Phase 1 study of the Moderna COVID-19 Vaccine retained high levels of neutralizing antibodies through 119 days following first vaccination (90 days following second vaccination).
When did the company submit its Emergency Use Authorization (EUA) Application?
On November 30, Moderna filed for EUA with the FDA as well as a Conditional Marketing Authorization (CMA) application with the European Medicines Agency.
When did the FDA authorize emergency use of the COVID-19 vaccine?
Just over a couple weeks later on December 18, 2020 the U.S. FDA authorized the emergency use of the vaccine product for individuals 18 and up in age. Thereafter the company received authorization for the COVID-19 vaccine from health agencies in Canada, Israel, the EU, the UK, Switzerland, Singapore and Qatar. They have additional authorizations under review, including the World Health Organization.
What kind of revenue has the investigational product generated?
The company recently reported that expected revenues should be in the $18.4 billion range for this year. If this occurs, this will convert the company to a profitable organization, the first time since its inception in 2010.
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