Invivyd, Inc. (Nasdaq: IVVD) has submitted a Citizen Petition to the U.S. Food and Drug Administration (FDA) challenging the agency to evolve its approach to COVID-19 prevention by placing greater emphasis on monoclonal antibodies (mAbs) alongside vaccines. The petition, announced on May 14, 2025, calls for a reassessment of COVID-19 vaccine efficacy data in light of significant changes in both population immunity and viral evolution.
The biopharmaceutical company argues that the current landscape of COVID-19 prevention requires updated strategies that reflect the endemic nature of the virus. According to Invivyd, Americans will need a "robust arsenal" to manage COVID-19 and other viral infectious diseases "for decades to come."
Changing Immunity Landscape
Invivyd highlights three critical changes that have occurred since the original COVID-19 vaccine trials were conducted in 2020:
First, the immunological status of the American population has fundamentally shifted. When initial vaccine efficacy studies were conducted, Americans were immunologically naïve to SARS-CoV-2. Today, virtually all Americans have some form of immunological memory, either from vaccination or natural infection.
Second, the virus itself has evolved significantly. During the original vaccine field studies, SARS-CoV-2 progressed from the Wuhan strain through Delta lineages, which were highly susceptible to human immune pressure. By late 2021, the emergence of immune-evasive Omicron variants changed the game. Invivyd notes that "vaccines produce lower antiviral titers following vaccination against Omicron lineages than they did against original Wuhan lineages."
Third, scientists now better understand the biological mechanisms behind the rapid waning of vaccine efficacy over time, which the company argues necessitates longer-term clinical evaluations rather than the short-term studies that informed current product labels.
The Case for Monoclonal Antibodies
In contrast to the outdated vaccine efficacy data, Invivyd points out that developers of monoclonal antibody COVID-19 prophylaxis medicines have conducted more recent and relevant studies. These include "placebo-controlled safety, antiviral activity, and efficacy studies in contemporary, seropositive populations, against evasive virus, and over the long term."
The company received emergency use authorization (EUA) from the FDA for a monoclonal antibody in March 2024, positioning itself as a key player in the non-vaccine COVID-19 prevention space.
Specific Recommendations to FDA
Invivyd's petition makes several specific recommendations:
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The FDA should evaluate COVID-19 mRNA vaccine effectiveness through new clinical trials that:
- Include randomized, placebo-controlled designs with seropositive patients in both study and placebo arms
- Test efficacy against contemporary immune-evasive Omicron variants
- Measure efficacy over a duration of at least six months
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The FDA should clarify that Biologics License Application (BLA) approval for preventative mAbs can be appropriately based on serum virus neutralizing antibody (sVNA) titers as surrogate endpoints.
"Such a data-driven approach would resemble the process undertaken to support modern monoclonal antibody development," the company states. "This approach is critical to ensure that COVID-19 vaccines maintain a positive risk-benefit profile based on contemporary data."
Potential Impact on COVID-19 Prevention
Invivyd argues that "leveling the playing field" between vaccines and monoclonal antibodies would enable companies like itself to "more rapidly develop and scale non-vaccine solutions for the major populations of Americans that would benefit from high quality alternatives."
The company suggests that using serum virus neutralizing antibody titer data from clinical trials as the basis for approval would offer substantial benefits to patients, vulnerable populations, healthcare providers, sponsors, and regulators, particularly as virus variants continue to evolve.
About Invivyd
Invivyd describes itself as a biopharmaceutical company "devoted to delivering protection from serious viral infectious diseases, beginning with SARS-CoV-2." The company employs a proprietary integrated technology platform designed to assess, monitor, develop, and adapt antibodies.
The FDA's response to Invivyd's Citizen Petition, including whether it will implement any of the company's recommendations, remains to be seen. The petition represents a significant challenge to current regulatory approaches to COVID-19 prevention and could potentially reshape how both vaccines and monoclonal antibodies are evaluated and authorized in the endemic phase of the pandemic.
