PURPOSE:

• The FDA has issued an Emergency Use Authorization (EUA) for the Moderna COVID-19 (mRNA-1273)
  • For ages ≥18 years to prevent COVID-19
  • Lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccine encoding the stabilized prefusion spike glycoprotein of SARS-CoV-2
  • 2 doses (100 μg, 0.5 mL each) administered IM 28 days apart
• The body of evidence for the Moderna COVID-19 vaccine was primarily informed by one large trial
• Oliver et al. (MMWR, 2020) on behalf of ACIP, assessed the data and report on the findings and ACIP interim recommendations 

METHODS:

• Randomized, double-blind, placebo-controlled Phase III clinical trial
• Participants
  • ≥18 years
  • Pregnant and lactating women were not included in this dataset
• Randomized 1:1 to 2 groups
  • Vaccine
  • Saline placebo
• Primary study outcome
  • Efficacy: Prevention of symptomatic, laboratory-confirmed COVID-19 among persons without evidence of previous SARS-CoV-2 infection

RESULTS:

• 30,351 enrolled participants
  • Vaccine: 15,185
  • Placebo: 15,166
• Age: 18 to 95 (median: 52 years)

Vaccine Efficacy

• The vaccine demonstrated high efficacy after 2 doses (7 week follow-up)
  • Vaccine: 11 cases
  • Placebo: 185 cases
  • Vaccine efficacy: 94.1% (95% CI, 89.3% to 96.8%)
• In this final scheduled analysis (9 week follow-up) similar results were obtained
  • Vaccine efficacy: 94.5% (95% CI, 86.5 to 97.8)
• High efficacy was observed across age, sex, race, and ethnicity categories and among persons with underlying medical conditions

Adverse Events

• Systemic adverse reactions were more commonly reported after the second dose
• More frequent and severe in persons aged 18 to 64 years than in those aged ≥65 years
• Most local and systemic adverse reactions occurred within the first 1 to 2 days after vaccine receipt and resolved in a median of 2 to 3 days
• Severe local or systemic adverse reactions (grade ≥3 reactions)
  • Occurred more commonly in vaccine recipients (21.6%) vs placebo recipients (4.4%)
  • Among vaccine recipients, 9.1% reported a grade ≥3 local injection site reaction, and 16.5% reported a grade ≥3 systemic adverse reaction
• Serious adverse events: Death | Life-threatening | Requires inpatient hospitalization or prolongation of existing hospitalization | Results in persistent disability/incapacity
  • No difference between groups (1% in both)
• No specific safety concerns were identified in subgroup analyses by age, race, ethnicity, underlying medical conditions, or previous SARS-CoV-2 infection
• Detailed summary of safety data and adverse events can be found in ‘Learn More-Primary Sources’ below

CONCLUSION:

• Based on the above data, ACIP issued an interim recommendation for the use of the Moderna vaccine
• ACIP concluded that

COVID-19 is a major public health problem and that use of the Moderna COVID-19 vaccine is a reasonable and efficient allocation of resources. Whereas there might be uncertainty about how all populations value the vaccine, it was determined that for most populations, the desirable effects outweigh the undesirable effects, making the vaccine acceptable to implementation stakeholders 

Learn More – Primary Sources:

The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Moderna COVID-19 Vaccine — United States, December 2020

Local Reactions, Systemic Reactions, Adverse Events, and Serious Adverse Events: Moderna COVID-19 Vaccine

FDA Takes Additional Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for Second COVID-19 Vaccine

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine (NEJM)

Related ObG Topics:

Safety and Efficacy Data of BNT162b2 COVID-19 Vaccine

Coronavirus and Pregnancy: CDC Guidance and Professional Recommendations