Pfizer recently announced that the large American pharmaceutical company along with German partner BioNTech SE (BNTX) has applied to the U.S. Food and Drug Administration (FDA) for Emergency Use Authorization (EUA) for an additional booster dose targeted for adults aged 65 and up who have received an initial booster of any of the authorized or approved COVID-19 vaccines.

TrialSite provides a brief breakdown of this report by Pfizer.

What clinical trials are Pfizer using to justify the EUA?

None. Rather the company is basing the EUA on a couple of sets of real-world data sets derived from Israel analyzing a time when the Omicron variant was in broad circulation.  According to the New York-based drug manufacturer, this data set evidence that an additional mRNA booster boosts immunogenicity and lowers rates of confirmed infections and severe illness.

What’s more detail on this real-world data?

According to the Pfizer application, they analyzed Israeli Ministry of Health records covering 1.1. million adults aged 60 and above with no known history of COVID-19 and who were eligible for a fourth additional dose booster.

The company presents to the world that the data indicates rates of infections were twice as low while rates of severe illness four times lower among those people who received an additional booster dose of BNT162b2 (Comirnaty) at least four months after an initial booster (third dose) compared to those who received only one booster dose.

The company also declares that data from an ongoing observational (open-label, non-randomized) study involving healthcare workers aged 18 and above at a single Israeli study center were vaccinated with three doses of BNT162b2.  They report that out of the 154 out of 700 participants who received the fourth boost of BNT162b2 at least four months after the initial boost (third dose), neutralizing antibody titers boosted by 7-8-fold at two and three weeks after the additional booster (fourth) dose compared to five months after the initial booster (third) dose.

The company points out that the additional boost led to an 8-fold and 10-fold boost in neutralizing antibody titers against the Omicron variant (B.1.1.529) at one and two weeks after the additional booster dose respectively, compared to five months after the initial booster.

What about safety?

The company doesn’t say much here other than to say there “the study revealed no new safety concerns in individuals who received an additional booster dose of the vaccine. They do note the existing safety concerns in the company’s official press release.

What about long-term safety? Has there been any study looking into this?

Not at all.  No one knows what the impacts of four doses on the elderly will be in the aggregate over time. Pfizer and the FDA look at each set of data as discrete sets, not considering the connective, accumulated impacts that all these inoculations might have on the human body. 

What other evidence does Pfizer point to?

Well, they point to studies showing that their product’s effectiveness wanes as justification to approve and administer even more vaccines. For example, the company also points out that data from a Kaiser Permanente Southern California study suggests that effectiveness against both symptomatic COVID-19 and severe disease caused by Omicron wanes 3 to 3 to 6 months post the third jab of the Pfizer dose.

They use this as a rationale to drive more use of the same product.

But what about the other Omicron-specific product—is this EUA for that?

No, that is still in development.

So, what’s the bottom-line rationale that the FDA would use to authorize this EUA?

The Israel data suggest that those people that accepted an additional booster dose of BNT161b2 at least four months after an initial third booster dose could restore antibody titers to peak post-third dose titer levels while improving protection against both infection and severe disease in people aged 60 and above in the Eastern Mediterranean nation.  While they argue the data indicates no change in safety profile.

Meanwhile, they use the failings in their own product, showcased by the Kaiser study, to bolster their argument to the FDA. However, they remind that the FDA hasn’t yet reviewed that data.

What’s the current Pfizer-BioNTech COVID-19 vaccine authorized dosage?

It’s authorized as a single booster dose administered at least five months post completion of the primary series of the BNT162b2 (Comirnaty) mRNA-based vaccine to people aged 12 and up.  Note a single dose can also be administered to people aged 18 and up who have completed a primary vaccination with another authorized or approved COVID-19 vaccine.

What’s the broader general argument for continuous vaccination?

Those people who are kept up to date with their boosters are generally more protected against serious or deadly SARS-CoV-2 infections than those that are not.

Is the Pfizer-BioNTech vaccine approved in the USA? What about corporate liability?

Yes. However, there is still no liability to the company under the PREP Act as TrialSite has reported

Does Pfizer acknowledge the risk of cardiovascular-based serious adverse events, albeit rare?

Yes. Pfizer acknowledges that males under 40 face higher risk for myocarditis and pericarditis from the mRNA-based vaccine.  They declare that for most of the people receiving the vaccine these symptoms dissipate within a few days, mostly after the second dose. 

Does Pfizer discuss any deaths that have been associated with the vaccine?

No. Not in the American market. TrialSite has chronicled a handful of deaths of young persons in Vietnam.

What’s TrialSite’s view on the vaccine efficacy? Safety?

TrialSite believes that the Pfizer-BioNTech vaccine does reduce the risks of hospitalization and death.  In fact, for the immunocompromised and the elderly it would appear this is especially the case as they are higher up the risk curve.  On the other hand, TrialSite questions a one-size-fit-all approach inclusive of mandates threatening workers’ employment because the vaccine doesn’t stop community viral transmission within weeks where Omicron is in circulation.  This was the result of waning vaccine effectiveness recorded with the BNT162b2 product also called Comirnaty.

Pfizer’s CEO declared this problem only commenced with Omicron, but this is not the case—waning vaccine effectiveness started during the Delta surge during the summer of 2021.  Thereafter for example Israel experiences huge surges with large numbers of breakthrough infections and hospitalizations.

The risk curve impacts the risk-benefit analysis for vaccination—the higher the risk the more compelling the vaccine value proposition over concerns of SARS-CoV-2 infection (about 90% of COVID-19 cases are mild to moderate in nature).  So, therefore Pfizer is submitting the EUA for the elderly and not younger people. For younger people, the risk-benefit analysis may differ from those who are more vulnerable.   But in many locations, people may not have an option to make their own medical decisions.  What if an employer or school mandates a third or fourth jab? The only possible option becomes the courts to challenge such an action.

Some factors that weigh in favor of the vaccine are the impacts of long covid (anywhere from 10-30% of those who are infected with COVID-19 succumb to this unfortunate ailment with a variety of at times bizarre symptoms) while with Delta and even more with the highly transmissible Omicron children became more hospitalized hence the risk-benefit analysis changed when compared to the earlier variants and wildtype.  Yet child hospitalization remains rare.

Moreover, the social determinants of health are important factors. America’s health system doesn’t benefit all people the same for example.  Blacks died at higher rates than whites during the pandemic.  In some locations such as Los Angeles at certain times, Blacks in the southeastern parts of the county were dying at nearly six times the rates of wealthy whites on the western edges on the coast. Poor rural whites also have struggled in the southern part of the United States for example based on a recent TrialSite interview.

Critics would argue that many of these deaths involved other comorbidities and that they were not deaths caused by COVID-19.  Yet many emergency physicians saw firsthand that the SARS-CoV-2 infections triggered the cycle that became deadly.

While over 13,000 deaths have been recorded in the Centers for Disease Control and Prevention (CDC)  Vaccine Adverse Event Reporting System (VAERS) health authorities, including the CDC deny that most of these are associated with the novel gene-based vaccine product.  Yet the authorities haven’t proven that these incidents are not associated with the vaccine. Some outspoken critics argue that this death count is vastly undercounted.

Many elderlies are concerned about taking yet another dose of this mRNA regimen.  What if boosters become mandatory?  This is not an easy situation for anyone and compounding the problem are onerous factors such as a serious federal overreach into health care, forced mandates, disruption of the physician-patient relationship at the local level, corporate liability shields promulgated by the state (federal government), and unprecedented politicization (unfortunately raising trust issues with long-established government sources of truth) suggesting that all people should learn as much as possible about not only the pandemic and their health care risks but also about these novel products while wherever possible verifying assumptions with physicians that are objective and open to all the data as it unfolds during the pandemic.

Securing multiple points of view are imperative in this environment as is ensuring that one visits multiple, credible media sources, not just the ones that align with one’s point of view. Often there isn’t just one black or white truth but shades of grey.

What references do Pfizer cite?

Ferdinands JM, Rao S, Dixon BE, et al. Waning 2-Dose and 3-Dose Effectiveness of mRNA Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Adults During Periods of Delta and Omicron Variant Predominance – VISION Network, 10 States, August 2021-January 2022. MMWR Morb Mortal Wkly Rep. 2022 Feb 18;71(7):255-263. DOI: 10.15585/mmwr.mm7107e2. PMID: 35176007; PMCID: PMC8853475.

Chemaitelly H, Ayoub HH, AlMukdad S, et al. Duration of protection of BNT162b2 and mRNA-1273 COVID-19 vaccines against symptomatic SARS-CoV-2 Omicron infection in Qatar. medRxiv. 2022. doi:10.1101/2022.02.07.22270568

Tartof, SY, Slezak, JM, Puzniak L, et al. BNT162b2 (Pfizer–Biontech) mRNA COVID-19 Vaccine Against Omicron-Related Hospital and Emergency Department Admission in a Large US Health System: A Test-Negative Design. Available at SSRN: https://ssrn.com/abstract=4011905 or http://dx.doi.org/10.2139/ssrn.4011905

Andrews N, Stowe J, Kirsebom F, et al. Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. N Engl J Med. 2022 Mar 2. doi: 10.1056/NEJMoa2119451. Epub ahead of print. PMID: 35249272.

UK Health Security Agency. COVID-19 vaccine surveillance report – Week 9, 3 March 2022. Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1058464/Vaccine-surveillance-report-week-9.pdf

Regev-Yochay G, Gonen T, Gilboa M, et al. 4th Dose COVID mRNA Vaccines’ Immunogenicity and Efficacy Against Omicron VOC. medRxiv. 2022:2022.02.15.22270948. doi:10.1101/2022.02.15.22270948

Bar-On YM, Goldberg Y, Mandel M, et al. Protection by 4th dose of BNT162b2 against Omicron in Israel. medRxiv. 2022:2022.02.01.22270232. doi:10.1101/2022.02.01.22270232

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