FDA Panel Votes Unanimously to Support Moderna COVID-19 Vaccine Booster Dose

Updated at 3 PM EST: The FDA VRBPAC panel voted 19-0 to back available data’s support of the efficacy and safety of the Moderna COVID-19 vaccine mRNA-1273 as a 50mcg booster dose in certain high-risk populations.

The independent expert panel vote—which concluded a daylong deliberation of data made available by Moderna as part of the company’s pursuit of an EUA expansion to include the booster dose—supports the use of a third, lesser dose of mRNA-1273 ≥6 months after initial vaccine regimen completion for the following populations:

• Individuals aged 65 years and older
• Individuals aged 18 to 64 years old at high risk of severe COVID-19
• Individuals aged 18 to 64 years old at high risk of frequent SARS-CoV-2 exposure due to institutional or occupational background

With the supporting VRBPAC vote, the FDA will most likely grant emergency authorization to Moderna for the indicated booster dose use in the coming months. Moderna would become the second vaccine developer to receive an EUA for a clinically-evidenced booster dose, after Pfizer-BioNTech received such an indication for its mRNA vaccine BNT162b2 (Comirnaty) last month.

Updated at 1 PM EST: A presentation from Moderna on the supporting evidence of a booster COVID-19 vaccine dose highlighted the rationale of strategy behind a would-be FDA-authorized third dose.

Presented by Jacqueline Miller, MD, Therapeutic Area Head of Infectious Disease for Moderna, to the VRBPAC panel, the presentation included a breakdown of the proposed use of the mRNA-1273 booster dose. Administration of a single 50 mcg dose ≥6 months after completion of the initial 2-dose regimen would be allotted to the following populations:

• Individuals aged 65 years and older
• Individuals aged 18 to 64 years old at high risk of severe COVID-19
• Individuals aged 18 to 64 years old at high risk of frequent SARS-CoV-2 exposure due to institutional or occupational background

Aside from the standard dosing regimen schedule, which was implemented in the company’s original Emergency Use Authorization (EUA), Moderna additionally offers a unique booster-dose schedule for eligible immunocompromised adults: 100mcg dose 1 at baseline, 100mcg dose 2 at 4 weeks, then 100mcg dose 3 at ≥1 month.

Since the EUA was granted to Moderna in December 2020, 191 million-plus doses of mRNA-1273 have been distributed nationally, Miller stated. More than 69 million Americans are fully vaccinated with mRNA-1273, and approximately 1.5 million have received a third dose.

Updated, unblinded data from the company’s phase 3 efficacy trial—which provided supporting data for the company’s EUA last year—presented at the VRBPAC meeting showed full vaccination with mRNA-1273 was associated with a 93.2% vaccine efficacy in preventing COVID-19 through a median 5.3 months of follow-up versus placebo.

The vaccine was also 98.2% effective in preventing severe COVID-19 at the median follow-up date.

“However, while the team was preparing the BLA (Biologics License Application) submission, the Delta variant had emerged as a variant of concern in the United States,” Miller said.

An assessment of breakthrough infection data from the efficacy trial showed 250 breakthrough infections were observed in trial participants in July and August 2021. Because patients in the trial were staggered in enrollment, the infections occurred a median 8 or 13 months after first dose.

Comparing the early and later vaccinated groups’ infections, however, investigators observed a 36.4% overall decrease in breakthrough infections in later-vaccinated patients (49.0 cases per 1000 person years) than earlier-vaccinated patients (77.1 per 1000).

Additionally, exploratory data assessing antibody persistence and boosting with 50mcg mRNA-1273 showed that neutralizing antibodies waned significantly in the 6-8 months post-second dose relative to the first month after the second dose—particularly among patients exposed to the Beta, Gamma, or Delta variants.

However, in the 14 days after booster dose administration, neutralizing antibodies increased up to 44-fold against the original SARS-CoV-2 strain and variants of concern.

Updated at 11 AM EST: The US Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) is meeting Thursday, October 14, to discuss the potential amendment to Moderna’s COVID-19 vaccine Emergency Use Authorization (EUA) that would allow for booster dose administration in adults aged 18 years and older.

The day-long public meeting will conclude with a vote from the VRBPAC panel either supporting or rejecting the proposed amendment, based on currently available data. A supporting vote from the panel of independent experts would likely influence the FDA’s authorization of the Moderna booster dose for mRNA-1273 in the coming weeks—thereby making it the second COVID-19 vaccine authorized for supplemental dosage to compensate for waning immunity in certain populations.

Follow the developments and discussion from the VRBPAC meeting today on Contagion, which will be covering the meeting through the panel’s vote this evening.