Regulatory Focus™ > News Articles > 2021 > 9 > In advance of adcomm, Pfizer makes its case for Comirnaty booster

In advance of adcomm, Pfizer makes its case for Comirnaty booster

Posted 15 September 2021 | By Kari Oakes 

In advance of adcomm, Pfizer makes its case for Comirnaty booster

In briefing documents made available on Wednesday in advance of a US Food and Drug Administration (FDA) meeting, Pfizer made the case that a third dose of its COVID-19 vaccine would address an unmet public health need in the face of high and persistent levels of Delta variant breakthrough infections among the vaccinated.
Pfizer’s application for a supplemental biologics license application (sBLA) for Comirnaty, the messenger RNA (mRNA) COVID-19 vaccine it co-developed with BioNTech, will be the subject of a 17 September meeting of the Vaccines and Related Biologic Products advisory committee (VRBPAC) to the US Food and Drug Administration (FDA).
Both Pfizer and FDA acknowledge that immunogenicity against both wild-type SARS-CoV-2 and the Delta variant, as measured by geometric mean titers, leaps after a booster dose. The sponsor and FDA also concur that adverse events after a booster dose are not worse, overall, than those seen after the second dose during clinical trials. No signal for myocarditis or pericarditis has been detected after a booster.
With clinical trial and population-level data alike, it is difficult to tease out how much of the rise in breakthrough infections can be attributed to the Delta variant’s greater transmissibility and ability to evade immune defenses, and how much is caused by immunity that declines as time after vaccination passes.
Pfizer, for its part, turned to data from Israel to help unpack this issue. Israel achieved high community rates of vaccination earlier than most countries and has therefore had the opportunity to see how the vaccinated fare against the Delta variant when large portions of the population are months past their second vaccination.
The Pfizer briefing includes an examination of real-world data from Israel that “showed a correlation between time since vaccination and the incidence of breakthrough infections among fully-vaccinated individuals ≥16 years of age,” during June and July 2021, when the Delta variant predominated SARS-CoV-2 infections in Israel. According to Pfizer, after adjusting for potential demographic and clinical confounders, breakthrough infection was 53% more likely to occur in those vaccinated earlier versus those vaccinated later. These results were statistically significant (P less than .001) and did not vary across age groups.
In another way of looking at the data, Israeli investigators found a 2.26-fold increased risk of breakthrough infection for people vaccinated in January 2021, compared with those vaccinated in April 2021.
FDA, however, looked at a Pfizer post hoc analysis of clinical trial enrollees who experienced COVID-19 in June and July 2021. The agency had asked for this analysis, which compared cases between those who completed the 2-dose primary vaccine series earlier with those who received their doses later. The latter group were made up of participants who were originally in the placebo arm and then crossed over to receive the vaccine after unblinding.
This analysis found that cases were higher in the summer months (43.4 per 1,000 person-years), even among the recently vaccinated, than they were before the Delta surge, when they ran at 12.6 per 1,000 person-years. Over 60% of patients evaluated during this earlier period were more than 4 months out from completion of the primary 2-dose series.
“This observation suggests that while waning immunity is one potential factor that may have contributed to the higher incidence breakthrough cases during the Delta variant surge, it is possible that other factors (e.g., dynamics of Delta variant transmission and potential differences in vaccine effectiveness against the Delta variant vs. strains circulating during the placebo-controlled portion of the trial) may also have contributed,” wrote FDA.
Both FDA and Pfizer do agree that individuals who have completed the primary 2-dose series still seem to be largely protected against hospitalization, though Pfizer argues that increasing rates of breakthrough infection may be a harbinger of more serious COVID-19 breakthrough cases to come, as immunity continues to wane.
The meeting will be broadcast on YouTube, Facebook and Twitter, in addition to FDA’s usual webcast. FDA is not obligated to follow the recommendations of its advisory committee members, though it usually does.
VRBPAC briefing materials


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