Invivyd announced positive in vitro neutralization data showing that PEMGARDA (pemivibart), its FDA-authorized monoclonal antibody for COVID-19 pre-exposure prophylaxis, maintains neutralizing activity against the currently dominant XFG variant of SARS-CoV-2. The company also reported similar results for its next-generation candidate VYD2311, as COVID-19 infections continue rising across much of the United States.
Sustained Efficacy Against Evolving Variants
The new data demonstrates that XFG, like all dominant variants over the past three years, did not generate meaningful changes to the in vitro neutralization activity of either pemivibart or VYD2311. According to Invivyd, the epitopes targeted by both monoclonal antibodies remain structurally intact, maintaining their ability to neutralize the virus.
"COVID-19 activity is once again on the rise across much of the United States, with wastewater data and forecasting models pointing to sustained growth in infections," said Robert Allen, Ph.D., Chief Scientific Officer of Invivyd. "Against this backdrop, we are pleased but not surprised that pemivibart has continued to demonstrate neutralizing activity against the currently dominant XFG variant."
The company estimates that every clinical variant reported in the CDC COVID Data Tracker since the Omicron BA.2 lineage has been susceptible to pemivibart, even if untested, due to the consistent structural integrity of the targeted epitope.
Rising COVID-19 Activity Drives Clinical Need
Current surveillance data indicates significant COVID-19 activity across the United States. Wastewater monitoring shows high or very high viral activity levels in 12 states as of early August, while CDC forecasting models estimate that COVID-19 infections are growing or likely growing in 34 states with zero states showing declining trends.
"For people whose immune systems may not get enough protection from vaccines such as those on immunosuppressive therapies and those undergoing cancer treatment, each new COVID-19 wave can create additional challenges and disrupt care," commented Tim Lee, Chief Commercial Officer of Invivyd.
Next-Generation Antibody Development
VYD2311, Invivyd's next-generation monoclonal antibody candidate, demonstrated similarly consistent and highly potent neutralization results against XFG. The candidate was engineered using the company's proprietary integrated technology platform through serial molecular evolution designed to optimize neutralization of contemporary virus lineages.
VYD2311 leverages the same antibody backbone as pemivibart but offers enhanced potency. The pharmacokinetic profile and antiviral potency of VYD2311 may enable delivery of clinically meaningful titer levels through more patient-friendly administration routes, such as intramuscular injection, compared to PEMGARDA's current intravenous administration.
Regulatory and Clinical Context
PEMGARDA (pemivibart) injection (4500 mg) is authorized by the FDA under Emergency Use Authorization for pre-exposure prophylaxis of COVID-19 in adults and adolescents 12 years and older weighing at least 40 kg who have moderate-to-severe immune compromise. The authorization applies to patients unlikely to mount adequate immune responses to COVID-19 vaccination due to medical conditions or immunosuppressive treatments.
The neutralization data against XFG and other circulating viruses will be provided to the FDA imminently, with anticipated inclusion in the PEMGARDA Fact Sheet for Healthcare Providers. PEMGARDA targets the SARS-CoV-2 spike protein receptor binding domain, inhibiting virus attachment to the human ACE2 receptor on host cells.
Technology Platform Validation
The consistent neutralizing activity across SARS-CoV-2 evolution validates Invivyd's molecular design strategy. Both pemivibart and VYD2311 showed positive neutralization data against other currently circulating variants including NB.1.8.1 ("Nimbus"), LF.7.9, and LP.8.1, with no non-responsive viruses identified or anticipated.
"The demonstrated stability of the epitopes our monoclonal antibodies target across SARS-CoV-2 evolution underscores the strength of our molecular design strategy and our capability in creating high-barrier-to-resistance medicines," Allen noted.
PEMGARDA was engineered from adintrevimab, Invivyd's investigational monoclonal antibody with a robust safety data package that provided evidence of clinical efficacy in global Phase 2/3 clinical trials for COVID-19 prevention and treatment.
