Data from an ongoing clinical trial found that a booster dose of Moderna’s COVID-19 vaccine produced an immune response with no serious safety concerns, FDA staff said in briefing documents released on Tuesday.
However, similar to the Pfizer COVID-19 booster trial, the sample size is small, with 149 participants receiving a half-dose 50 μg booster at 6-8 months following the two-dose primary series, and clinical effectiveness is being inferred based on immunogenicity data.
The Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet on October 14 to discuss a Moderna booster dose for certain populations. Having learned from its experience with Pfizer, the FDA is asking VRBPAC to consider emergency use authorization (EUA) of a booster dose at least 6 months after the two-dose primary series in:
- Adults ages 65 and older
- Adults ages 18-64 at high risk for severe COVID
- Adults ages 18-64 whose occupational and institutional exposure puts them at risk of COVID exposure, such as healthcare workers and teachers
Primary support for a half-dose booster of Moderna vaccine comes from a phase II trial, P201, where participants were randomized to receive either a two-dose 50 μg series, 100 μg series, or placebo (part A), and then a 50 μg booster dose (part B).
Overall, 149 adults received the two-dose 100 μg series, which is the dose authorized under EUA, plus the booster dose and were evaluated for immunogenicity. They were a mean age of 53, about three-quarters were between ages 18-65, and 60% were women. Nearly all (95%) were white, and 14% had obesity. Median interval between completion of the primary series and the booster dose was about 7 months.
FDA staff noted adults with a history of chronic cardiovascular disease, chronic pulmonary disease, HIV, diabetes, and a history of hypertension were excluded from participating in study P201.
They added that “immunogenicity data from a random subset of P301 participants were used as the reference group for immunobridging analyses to infer vaccine effectiveness of the booster dose.” P301 was the phase III study that supported Moderna’s EUA for the two-dose vaccine in December.
Notably, study P201 participants were less racially and ethnically diverse, had a lower median BMI, a lower rate of obesity, and a lower percentage of men, though FDA staff said these differences were “unlikely to impact the clinical results from the safety and primary immunobridging analyses.”
While “immunobridging analyses against the D614G strain met the pre-specified success criteria for the [geometric mean titers] ratio,” FDA staff added that in seroresponse rates after the booster dose compared to dose 2, “the pre-specified success criterion was not met,” as the difference in seroresponse rate was -10.5%, and the lower limit of the 95% CI had a criteria of less than -10%.
As with Pfizer’s data, FDA staff seemed less than impressed with Moderna’s data on booster effectiveness against the Delta variant, commenting, “Moderna proposes to infer effectiveness of the booster dose against the Delta variant from exploratory descriptive analyses of neutralizing antibody titers against this variant evaluated among booster dose recipients from study P201 Part B.”
Interestingly, there were 38 COVID-19 cases of 171 booster recipients reported during the Delta surge in study P201. Moderna performed a post hoc analysis of incidence of SARS-CoV-2 among participants originally randomized to Moderna vaccine (median 13 months post-dose 2) and the participants randomized to placebo and crossed over to Moderna (median 7.9 months, post-dose 2). The analysis showed 77.1 cases per 1,000 person-years versus 49.0 cases per person-years, respectively. However, this analysis was not independently verified by the FDA.
Examining safety, 344 participants contributed to the P201B safety set, 171 of whom received the 100 μg primary series, they noted.
FDA staff noted a higher rate of lymphadenopathy among adults ages 18-64 after the booster dose versus the primary series (24.8% vs 11.6%, respectively), but no evidence of “increased frequency or severity of local or systemic reactions after the booster dose, they said. Rates of lymphadenopathy were also significantly higher among adults ages 18-64 than adults ages 65 and up (24.8% vs 5.3%). Fatigue and headache were the most common unsolicited adverse events (AEs).”
There were no deaths or vaccine-related serious AEs, such as myocarditis, pericarditis, anaphylaxis, Bell’s palsy, or thrombotic or embolic events, in the 344 participants. They were followed up for a median of 5.7 months.
Similar to the Pfizer booster VRBPAC meeting, Thursday’s agenda indicates that Israeli researchers will present real-world evidence on the need for COVID-19 booster doses.