The FDA announced on Friday that there will be a meeting of the Vaccine Advisory Committee on October 22, with the agenda and materials to be released on October 20. We note that the latter date is just under two weeks from the election. The agency did announce that the meeting would address general standards and not a specific application. But, that could change. Additionally, recently, the agency released guidance on the agency’s proposed standards for approval of a vaccine for COVID-19. Those standards include a likely 50% efficacy with a lower confidence interval at or above 30%. This contrasts with the more common standard of over 80% and with a tighter confidence interval, although the original shingles vaccine was approved with a 50% efficacy. The shingles vaccine at that time, however, was limited to use in high risk patients such as those with a history of chicken pox and the elderly, those with immunosuppression and/or ongoing treatment for cancer. This is, however, a relatively low bar. While dependent on the baseline rate of infection, if known, the number of patients to be enrolled could be relatively small – in the low thousands. By way of example, a baseline incidence of 10% in the placebo group would translate to an incidence of 5% in the treated group for there to be efficacy provided that there were sufficient patents to make the plus or minus 20% confidence interval. Recent outbreaks on college campuses have shown an incidence of >10% once an outbreak has started, as from a frat party, with up to 1% to 5% among those not attending but with contact. At least three vaccines are in clinical trials in Brazil and other locations with high current incidences.
Additionally, in the guidance, FDA stated that the agency might approve the vaccine based on filing, under the Emergency Use Application (EUA) provisions, rather than require a complete statistical review, i.e., based on a summary of the efficacy. Under the rolling review provisions, many companies have already filed their manufacturing data. The guidance also waives certain toxicology requirements if the vehicle has previously been approved in another vaccine. Hence, for these applications, the summary clinical review could be the last threshold for marketing.
To that end, most companies will perform a blinded review of the data to identify whether the targets could be met which could precipitate early study closure. For instance, assume a baseline incidence of 10% in the population outside the study. Imagine that the rate within the study, blinded, is 7.5%. Divided equally, this could mean a 10% rate in the placebo and a 5% rate in the active. If so, based on the blinded analysis, the sponsor could issue a prediction as to when the company would close the study, file and, if approved on filing, market under an EUA.
In that light, and given that studies commenced in the U.S. and in high incidence areas in South America, one wonders whether such a prediction and preliminary data might be available for publication in late October. Data presented on October 22, including advisory committee comment, might then identify a potential date on which a vaccine could be available.
This all depends, of course, on the data. The most important being does the baseline incidence pan out? Is there a potential “half” reduction in one arm? And, then later, how protective will the vaccine be, even if antibodies are elicited to re-infection? There have been three recent reports of second infection – two were in screening, without symptoms, and potentially not infective. However, the third was dramatically ill. This shows that, in at least these three people, natural infection did not prevent reinfection. That is true for many illnesses for a host of reasons. But, in general, antibodies elicited from a highly targeted and highly effective vaccine can provide greater protection than natural infection.
To learn more about the issues raised by this client bulletin, please contact Jur Strobos at jstrobos@potomaclaw.com.
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