From Safe and Effective to “Uncomfortably Scant.”

The new bivalent booster must not be mandated because it is supported by no good data

Today’s guest post is by Dr. David McCune. It is on the topic of the impending Emergency Use Authorization of the bivalent booster. I find this action concerning. Problems include (a) no human data— that’s kind of a big deal (b) a vast age group, rather than targeting EUA to the eldest Americans and nursing home residents (it is just not true that 20 year olds are facing an emergency) (c) the White House is interfering with FDA and (d) FDA is not calling an outside advisory committee.

I believe these actions constitute a dangerous abuse of regulatory authority, and are a terrible precedent. Wake Forest has already announced it will mandate this booster, which just doubles downs on bad decision making. Finally, millions of Americans have just had BA.5 breakthrough— many after 3 or 4 COVID19 shots. It is implausible that a booster to an older version of Omicron will benefit them in the future. Here is David McCune, MD.

-Vinay Prasad MD MPH, from VP’s Observations and Thoughts

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On June 28th, 2022, the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee (VRBPAC) joined the Centers for Disease Control and Prevention (CDC) to mandate an unproven COVID booster for the fall of 2022. Almost nobody noticed.

Okay, not exactly. The truth is more complicated but only slightly less disturbing. The VRBPAC did make a recommendation, later endorsed by the FDA, that Pfizer and Moderna produce a new COVID “bi-valent” vaccine for this fall. If past form holds, the new booster (the 5th dose, if you’re keeping score at home) will become the CDC’s definition of “up to date vaccination status.” This has a downstream effect for all states that define work eligibility based on being “fully vaccinated” (e.g.: Washington, California), healthcare workers, and university students, all among those who may be required to re-re-boost. So while VRBPAC didn’t issue a direct mandate, the chain of events it set in motion renders that a distinction without a difference. 

This essay reviews that decision. It shows that neither sufficient safety nor effectiveness has been demonstrated, and that any move to require this new vaccine must be halted.

Limited evidence of effect. The latest booster is a “bi-valent” vaccine. This means it will contain a mix of mRNA from the original COVID strain and the currently circulating variant, Omicron BA.5. The drug companies mostly presented the VRBPAC with data on a bivalent vaccine using an earlier Omicron variant, BA.1. They had minimal data on specific vaccination using BA.4 or BA.5. Pfizer literally presented a slide of using BA.5 mRNA in an eight-mouse study they completed the day of the meeting. No human clinical data were presented to show that the bivalent boosters improve the prevention of severe disease. The hybrid vaccines reliably raised antibodies, but, as board member Dr. Ofer Levy put it, there was “no correlate of protection” against COVID.

No safety data. Literally none. When efficacy data are limited to a just-in-time eight-mouse study, it should come as no surprise there are no safety data for the new combination. The committee was uneasy, but ultimately chose to learn about any new side effects after rollout. This is particularly concerning for adolescent and young adult males. While they have among the lowest risk for COVID complications, they have the highest risk of vaccine-induced myocarditis. The booster will contain Omicron mRNA, and we have no idea whether this increases that risk. As Dr Cody Meissner put it “the question that bothers me (is that) we haven’t discussed safety, myocarditis. Might we increase the risk of that if we use a bivalent vaccine?” 

It’s not 2020 any more. The world has changed since that first emergency use authorization (EUA). COVID is still highly prevalent, but, as a committee member put it, increasingly resembling other cold viruses. At the beginning of the pandemic the US faced a virus against which there was no preexisting immunity or treatment. That is no longer the case. 

The current population, through a combination of vaccination, prior infection and treatment has increasingly broad resistance to SARS-CoV-2. With each new exposure, the risk of severe outcomes continues to fall. This was seen clearly in a slide by FDA, showing that, despite surges of COVID cases, the number of fatalities relative to the cases declined with each new wave. While there are still high-risk populations, the truth is that COVID is no longer an emergency for most people. 

Precedent. In choosing an untested new vaccine combination, the FDA opted for speed over evidence in the hope of providing protection from current and future variants. They discussed an ongoing series of boosters, with no clear metrics as to when this should end. The Moderna CEO confidently said a new bivalent vaccine would be ready in October “assuming no clinical requirements, no need to assess the vaccine at all.” Pfizer presented a slide envisioning a continual cycle of rapid vaccine approvals occurring within months, but relying on preclinical data only, no human studies required. The mRNA technology used by the vaccines can produce an unending stream of wonders, just as long as they aren’t held back by such petty considerations as “what happens when we give this to people?”

The Law: The Supreme Court upheld the Centers for Medicare & Medicaid Services (CMS) mandate for vaccinating healthcare workers in part because “a COVID–19 vaccine mandate will substantially reduce the likelihood that healthcare workers will contract the virus and transmit it to their patients.” Yet the VRBPAC didn't even begin to address the issue of transmission. The FDA is charged with ensuring the new combination is safe and effective. Based on the evidence presented, they can be sure of neither. All they can say is that a BA.5 bivalent vaccine raised antibody levels and the eight mice who received it lived long enough to have their blood drawn. Anything more is speculation.

This is not the standard the agency has previously used. Dr. Paul Offit, one of two “no” votes, summed up his discomfort when he described this as a new vaccine. “(I)t should be handled as a new product.” He expressed dismay that the data presented were “uncomfortably scant.” Instead of demonstrating safety prior to approval, the committee admitted “we’re only going to learn (about toxicity) when it is rolled out to large numbers of people.” A new and untested product was not under consideration when the Supreme Court upheld the CMS mandate. This is different.

Standards: We cannot allow a redefinition of “fully vaccinated” to include an untested new product. Using never-relinquished “emergency” power, the legal mechanisms are already in place for this rushed decision to acquire force of law. If we don’t stop and evaluate the clinical benefit of neverending boosters, then there’s no clear off ramp. The new bivalent vaccine may offer some protection to those at the highest risk, but it has not met the standard of proof for the general population. It must not become a requirement for employment, education, or any other aspect of public life.

The FDA has shifted its standard from “safe and effective” to “uncomfortably scant.” The VRBPAC should have required more. Now it’s the rest of us who need to yell “stop!”

David McCune is former career military physician and current practicing oncologist. He tilts at windmills regarding health, humanism and America at