Moderna, Inc. announced in a press release that it has completed 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), part of the NIH. The company also is providing an update on its strategy for addressing SARS-CoV-2 variants of concern.
While initial data confirms that the Moderna COVID-19 Vaccine (mRNA-1273) provides neutralizing activity against variants of concern, out of an abundance of caution, Moderna is pursuing two strategies against these variants, subject to U.S. Food and Drug Administration (FDA) review. First, the company is evaluating booster doses of vaccine to increase neutralizing immunity against the variants of concern. Moderna plans to evaluate three approaches to boosting, including:
· 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.
· A multivalent booster candidate, mRNA-1273.211, which combines mRNA-1273, Moderna’s authorized vaccine against ancestral strains, and mRNA-1273.351 in a single vaccine at the 50 µg dose level and lower.
· A third dose of mRNA-1273, the Moderna COVID-19 Vaccine, as a booster at the 50 µg dose level. The Company has already begun dosing this cohort with the booster.
Second, the company plans to 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.c
Consistent with the recently updated FDA Guidance for Industry, the company plans to evaluate immunogenicity and safety in participants who have not received a COVID-19 vaccine as well as participants in clinical studies who previously received the mRNA-1273 vaccine.
NIAID will conduct a Phase 1 clinical trial to determine if mRNA-1273.351 can boost immunity against the variants of concern. Moderna will provide doses of mRNA-1273.351 to the NIH. NIAID will initiate this study after receiving safe-to-proceed authorization from the FDA. NIAID will provide additional information when the trial begins, and details will also be available on clinicaltrials.gov. In parallel, the company will be conducting its own clinical studies to support regulatory filings for any booster vaccine or updated primary vaccine.
These studies will inform the company’s regulatory strategy with the U.S. FDA and regulatory agencies outside of the U.S. The current Moderna COVID-19 Vaccine protocol calls for two 100 µg doses.
A letter to the editor in the New England Journal of Medicine showed 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.1.351 variant relative to prior variants.
