The FDA has decided to not expand the existing EUA for Invivyd’s investigational monoclonal antibody (mAb), pemivibart (Pemgarda), to include treatment of mild-to-moderate COVID-19 for immunocompromised persons. The company had been seeking expansion for adults and adolescents who have moderate-to-severe immune compromise due to certain medical conditions such as cancer and organ transplant, and for whom alternative COVID-19 treatment options are not accessible or clinically appropriate.1
“Immunocompromised people who cannot access standard of care are once again left with no option for COVID-19 treatment. Pemivibart, in contrast to all other COVID-19 antibodies ever made, is active and in clinical use today in the US as authorized," Mark Wingertzahn, senior vice president of Clinical Development, Invivyd, said in a statement. "Pemivibart is safe enough for certain immunocompromised patients who are not currently sick with COVID-19, but it is now being withheld from those same immunocompromised patients fighting active COVID-19 infection purportedly because its measured antiviral activity is in-line with, but does not clearly exceed, the activity of its key comparator antibody adintrevimab, as well as other comparative mAbs.” 1
The company also said there is no change to the existing EUA for the monoclonal antibody for pre-exposure prophylaxis of COVID-19 in immunocompromised patients who have no other therapeutic options. The company received its EUA for that indication back in March of last year.2
Invivyd provided the FDA with analyses demonstrating comparable antiviral activity between pemivibart and adintrevimab, the key antibody of interest for immunobridging, as well as analyses demonstrating predicted pemivibart clinical efficacy in-line with prior authorized mAb therapeutics, and well above currently authorized convalescent plasma.1
Back in January the company announced pemivibart has continued to show consistent neutralization for almost 3 years, with no meaningful change to activity even with the dominant COVID-19 variant, XEC.3
What You Need to Know
The FDA declined Invivyd’s request to expand pemivibart’s emergency use authorization (EUA) to treat mild-to-moderate COVID-19 in immunocompromised individuals. The decision was based on pemivibart’s antiviral activity being comparable but not clearly superior to the comparator antibody, adintrevimab, despite its proven safety and ongoing use for pre-exposure prophylaxis.
Pemivibart continues to be authorized for pre-exposure prophylaxis in immunocompromised patients without other therapeutic options.
Pemivibart has demonstrated robust and sustained neutralizing activity against 39 distinct SARS-CoV-2 variants over nearly three years, including dominant strains like XEC.
Read More: A Monoclonal Antibodies' Prospective Place in the COVID-19 PrEP Market
“We designed pemivibart and our pipeline molecules to resist the effects of evolution,” Invivyd Chief Scientific Officer Robert Allen, PhD, said in a statement at that time. “Pemivibart has now demonstrated antiviral activity in neutralization assays representing thirty-nine distinct SARS-CoV-2 variants across almost three years of rapid virus evolution. The ongoing pemivibart activity, with minimal quantitative change in neutralization activity, especially as compared to predecessor medicines such as tixagavimab/cilgavimab (Evusheld), is incredibly reassuring and validating of our fundamental R&D engine and potentiates our ability to successfully drug this target for long periods of time despite evolutionary pressure.”3
Pemivibart is a half-life extended mAb. Pemivibart was engineered from adintrevimab, Invivyd’s investigational mAb that has a robust safety data package and provided evidence of clinical efficacy in a global Phase 2/3 clinical trial for the prevention and treatment of COVID-19. It is administered as an intravenous (IV) infusion with a dosage of 4500mg. Previously, the mAb has demonstrated in vitro neutralizing activity against major SARS-CoV-2 variants, including JN1, KP311, and XEC.3
References
1. FDA Declined Invivyd’s Request to Expand Existing Emergency Use Authorization of PEMGARDA (pemivibart) to Include Treatment of Mild-to-Moderate COVID-19 For Immunocompromised Persons Who Have No Alternative Therapeutic Options; No Change to the Existing PEMGARDA EUA for Pre-Exposure Prophylaxis of COVID-19 in Certain Immunocompromised Patients.Invivyd press release. February 24, 2025. Accessed February 24, 2025.
https://www.globenewswire.com/news-release/2025/02/24/3031027/0/en/FDA-Declined-Invivyd-s-Request-to-Expand-Existing-Emergency-Use-Authorization-of-PEMGARDA-pemivibart-to-Include-Treatment-of-Mild-to-Moderate-COVID-19-For-Immunocompromised-Persons.html
2. Invivyd Announces FDA Authorization for Emergency Use of PEMGARDA™ (Formerly VYD222) for Pre-exposure Prophylaxis (PrEP) of COVID-19. Invivyd press release. March 22, 2024. Accessed January 10, 2025.
https://investors.invivyd.com/news-releases/news-release-details/invivyd-announces-fda-authorization-emergency-use-pemgardatm
3.Invivyd Announces Continued Neutralizing Activity of PEMGARDA™ (pemivibart) Against Dominant SARS-CoV-2 Variant XEC. Invivyd press release. January 10, 2025. Accessed January 10, 2025.
https://www.globenewswire.com/news-release/2025/01/10/3007561/0/en/Invivyd-Announces-Continued-Neutralizing-Activity-of-PEMGARDA-pemivibart-Against-Dominant-SARS-CoV-2-Variant-XEC.html
