Invivyd, Inc. announced it has submitted a Citizen Petition with the U.S. Food and Drug Administration (FDA) calling on the Agency to evolve from historical approaches to the development of vaccines and monoclonal antibodies (mAbs) for COVID-19 prevention, in order to rebuild American’s trust in scientific data, public health recommendations, and preventatives, including mAbs and vaccines, when effective. Americans will need a robust arsenal to manage COVID-19 and other viral infectious disease for decades to come.

Over the last few years, Americans have undergone an extraordinary change, as has SARS-CoV-2. In 2020, Americans were immunologically naïve to any exposure to the virus that causes COVID-19 when original vaccine efficacy studies were conducted, but today virtually all Americans have some immunologic memory from either subsequent vaccination or infection from circulating virus.

Further, during the first two years of the pandemic, and critically, during the original vaccine field studies, the SARS-CoV-2 virus moved from Wuhan through Delta lineages, which were highly susceptible to human immune pressure, to highly immune evasive Omicron lineages beginning late 2021. Indeed vaccines produce lower antiviral titers following vaccination against Omicron lineages than they did against original Wuhan lineages.

Finally, the biological phenomena leading to the rapid waning of vaccine efficacy over months is now better understood than it was in 2020, requiring prospective long-term evaluation in clinical trials rather than the short-term studies that provide published vaccine efficacy estimates on product labels.

By contrast, developers of monoclonal antibody COVID-19 prophylaxis medicines, such as Invivyd, have conducted recent placebo-controlled safety, antiviral activity, and efficacy studies in contemporary, seropositive populations, against evasive virus, and over the long term.

Leveling the playing field can unlock the ability of industrial sponsors like Invivyd to more rapidly develop and scale non-vaccine solutions for the major populations of Americans that would benefit from high quality alternatives. With this in mind, Invivyd filed a Citizen Petition with FDA, urging FDA to evaluate anew COVID-19 mRNA vaccine effectiveness and consider new clinical trials that assess COVID-19 vaccines 1) in a randomized placebo-controlled trial conducted in a modern U.S. population that includes seropositive patients in both study drug and placebo arms; 2) against contemporary immune-evasive Omicron viruses; and 3) to measure efficacy over a duration of 6 months or longer to ensure adequate protection. Such a data-driven approach would resemble the process undertaken to support modern monoclonal antibody development. This approach is critical to ensure that COVID-19 vaccines maintain a positive risk-benefit profile based on contemporary data.

In addition, in order to optimize patient access to alternative preventative medicines like mAbs, the Citizen Petition recommends that FDA should make clear that Biologics License Application (BLA) approval is appropriate based on serum virus neutralizing antibody (sVNA) titers, which are gold standard surrogate endpoints. Use of sVNA surrogate data from a clinical trial as the basis for approval – traditional or accelerated – and translation of sVNA titer to estimates of clinical benefit as virus variants evolve, would offer substantial benefits to patients and vulnerable populations, healthcare providers and care teams, sponsors, and regulators.