Invivyd, Inc. has announced the formation of the SPEAR (Spike Protein Elimination and Recovery) Study Group, a collaborative research initiative with leading investigators to evaluate monoclonal antibody therapy for Long COVID and Post-Vaccination Syndrome. The study group was established following multiple independent reports suggesting clinical benefit from PEMGARDA (pemivibart) therapy in Long COVID patients.
Research Collaboration and Leadership
The SPEAR Study Group brings together key thought leaders in Long COVID research, including Dr. Michael Peluso from the University of California, San Francisco, Dr. Amy Proal from the Polybio Research Foundation and Mount Sinai Cohen Center for Recovery from Complex Chronic Diseases, and Dr. David Putrino from Mount Sinai's Cohen Center. These investigators will collaborate with Invivyd to design and execute clinical trials evaluating broadly neutralizing anti-SARS-CoV-2 spike protein monoclonal antibody therapy.
"It is now clear from a growing body of high-quality, peer-reviewed research that persistent spike protein or viral reservoirs can be identified in a meaningful portion of people with Long COVID," said Dr. Peluso. "For the first time in years, there is a company with the capability to explore this space using active, broadly neutralizing monoclonal antibodies."
Clinical Rationale and Patient Population
The initiative addresses a significant unmet medical need, with as many as 5% or more of Americans reporting recent Long COVID symptoms. The study group's formation was prompted by growing case reports and case series suggesting meaningful symptom relief or remission of Long COVID following PEMGARDA use, though these reports remain anecdotal and uncontrolled.
The research is based on the mechanistically plausible hypothesis that prolonged exposure to pathogenic SARS-CoV-2 spike protein or persistent viral material may drive disease in some patients. Both Long COVID and Post-Vaccination Syndrome populations have been found to have persistent SARS-CoV-2 spike protein and overlapping clinical manifestations.
Therapeutic Approach and Drug Candidates
PEMGARDA (pemivibart) is a half-life extended investigational monoclonal antibody currently authorized by the FDA under Emergency Use Authorization for pre-exposure prophylaxis of COVID-19 in certain immunocompromised individuals. The antibody targets the SARS-CoV-2 spike protein receptor binding domain, inhibiting virus attachment to the human ACE2 receptor.
PEMGARDA was engineered from adintrevimab, which demonstrated clinical efficacy in global Phase 2/3 trials for COVID-19 prevention and treatment. The antibody has shown in vitro neutralizing activity against major SARS-CoV-2 variants, including JN.1, KP.3.1.1, XEC and LP.8.1.
The study group also plans to evaluate VYD2311, a next-generation monoclonal antibody candidate that may offer more patient-friendly administration through intramuscular injection. VYD2311 was developed using Invivyd's proprietary technology platform and leverages the same antibody backbone as pemivibart.
Clinical Development Plans
The SPEAR Study Group intends to launch collaborative, multi-center translational clinical research as soon as practicable. Initial efforts will focus on rigorous, controlled assessment of monoclonal antibody safety, translational biology, and exploratory efficacy in patient populations characterized by persistent virus or circulating SARS-CoV-2 spike protein.
"Long COVID is a pervasive, debilitating, and underappreciated public health challenge affecting millions of adults and children in the U.S., with no approved treatments," said Marc Elia, Chairman of the Board at Invivyd. The company believes the research will be critical to exploring disease biology and evaluating efficacy endpoints that could enable registrational studies in the future.
Regulatory Pathway and Safety Considerations
Invivyd plans to meet with the FDA early in the third quarter to discuss rapid approval pathways for COVID-19 monoclonal antibodies. The company emphasizes that PEMGARDA is not currently authorized for Long COVID treatment, and the planned clinical research aims to generate data needed to inform future studies and potential regulatory pathways.
PEMGARDA carries a boxed warning for anaphylaxis, with the most common adverse reactions including systemic infusion-related reactions, hypersensitivity reactions, and local infusion site reactions. The emergency use authorization is based on immunobridging data rather than direct clinical efficacy studies in the target population.
The SPEAR Study Group represents a significant step toward potentially developing the first approved treatment for Long COVID, addressing a condition that has left millions of patients without therapeutic options.
