FDA Grants EUA to Monoclonal Antibody for PrEP of COVID-19 in Immunocompromised


The authorization was given to Invivyd’s pemivibart (Pemgarda), and it is indicated for adults and adolescents with moderate-to-severe immune compromised conditions.

The FDA announced it has granted an emergency use authorization (EUA) to pemivibart (Pemgarda, Invivyd) for the pre-exposure prophylaxis (PrEP) of COVID-19 for both adults and adolescents at least 12 years of age, and weighing at least 40 kg (88.1 lbs) who are immunocompromised.1

This monoclonal antibody (mAb), formerly known as VYD222, is indicated for those individuals who are unlikely to mount an adequate immune response to COVID-19 vaccination, and recipients of pemivibart should not be currently infected with or have had a known recent exposure to an individual infected with COVID-19.1

Pemivibart was developed by the biopharmaceutical company, Invivyd, and is administered as an intravenous (IV) infusion with a dosage of 4500mg. The monoclonal antibody is the first to receive an EUA based on a rapid immunobridging trial design that is expected to be repeatable to help address the need to mitigate ongoing viral evolution.1

What the Data Showed
The EUA is based from the company’s CANOPY trial, which was a phase 3 study that enrolled approximately 750 participants in 2 cohorts across multiple trial sites in the United States. The first group, (cohort A) enrolled approximately 300 participants who were significantly immunocompromised. These participants received pemivibart.2

The primary endpoints for this group were safety and tolerability and serum neutralizing titers against relevant SARS-CoV-2 variants at Day 28, which were calculated based on the pharmacokinetic concentration of pemivibart from the immunocompromised participants and the IC50 value for pemivibart against relevant SARS-CoV-2 variants.2

The company said primary efficacy analysis using the immunobridging approach compared data obtained in the CANOPY clinical trial to certain historical data from the company’s previous phase 2/3 clinical trial of adintrevimab (ADG20) for the prevention of symptomatic COVID-19, in which serum neutralizing titers correlated with observed clinical efficacy.2

Cohort B enrolled approximately 450 participants at risk of exposure to SARS-CoV-2. Participants were randomized 2:1 to receive pemivibart or placebo administered via IV infusion. The primary endpoints include safety and tolerability and the proportion of participants with RT-PCR-confirmed symptomatic COVID-19 through 6 months.2

The company previously reported that pemivibart produced high serum virus neutralizing antibody (sVNA) titer levels against the XBB15 variant in the immunocompromised cohort. The investigators also noted an encouraging, potential early signal of clinical protection from symptomatic COVID-19 which would be expected based on the high sVNA titer levels and dose selected.2

In its latest reporting, the company said the CANOPY trial was designed to utilize current relevant SARS-CoV-2 variants, and the most relevant SARS-CoV-2 variant circulating in the US at the time of the analysis (JN1), was selected as the variant for the analysis of the primary immunobridging endpoint.1

Initial results from cohort A (immunocompromised cohort) looking at the JN1 variant include:

  • The Day 28 calculated sVNA titer for pemivibart against JN1 was 7365 (90% CI: 7148, 7589).
  • The ratio between the Day 28 titer for pemivibart against JN1 of 7365 and a Day 28 adintrevimab reference titer of 8944 was 0.82 (90% CI: 0.80, 0.85), showing that immunobridging was established in the CANOPY clinical trial.
  • The Day 90 calculated sVNA titer for pemivibart against JN1, prior to redosing, was 3199 (90% CI: 2995, 3418).
  • The titers against JN1 are projected to stay above the reference titer of 3514 for approximately 77 days (median) following a single dose of pemivibart.
  • The range of titers achieved against JN1 for 3 months following administration of pemivibart were consistent with the titer levels associated with efficacy of other SARS-CoV-2 targeting mAbs in prior clinical trials.1

Results showed that the safety and tolerability profile of pemivibart remained favorable with no study drug related serious adverse events reported; adverse events attributed to pemivibart were Grade 1 or 2 (mild or moderate) in severity.2

What You Need to Know

This authorization is based on the CANOPY trial, demonstrating safety and efficacy in preventing symptomatic COVID-19 among immunocompromised and at-risk populations.

Pemivibart offers the potential of an unmet need for an additional preventive option for this population, including solid organ transplant recipients and those with hematological malignancies, who may have impaired responses to vaccines and are at higher risk for severe COVID-19 outcomes.

Invivyd, the biopharmaceutical company behind pemivibart, is prepared for the launch of the medication and plans further studies.

COVID-19 and the Immunocompromised

The immunocompromised have been especially challenged with COVID-19 in terms of severity and as well as a diminished effectiveness for the COVID-19 vaccines.

“People who are immunocompromised continue to be disproportionally impacted by COVID-19 even after receiving multiple vaccine doses,” Cameron R. Wolfe, MBBS, MPH, professor of Medicine, Transplant Infectious Disease at Duke University School of Medicine, said in a statement. “I’m excited to have Pemgarda as an additional COVID-19 preventive option for moderately to severely immunocompromised adult and adolescent patients, such as solid organ transplant recipients and those with hematological malignancies. These types of patients, among others, continue to have both an impaired response to vaccines and a higher risk for severe COVID-19 outcomes.”1

In 2023, the CDC published prevention measures in trying to reduce the incidence of COVID-19 for people who are immunocompromised.2

Although these are not new measures, these strategies serve as good reminders and include the following:

  • Get an updated COVID-19 vaccine
  • Improve ventilation and spend time outdoors
  • Learn about testing locations and treatment options before getting exposed or sick
  • Get tested if you been exposed to the virus or have symptoms
  • Wash your hands often
  • Wear a well-fitted mask and maintain a distance in crowded spaces.2

What Comes Next

Invivyd made some financial transactions ahead of the EUA, and is prepared for the launch of the pemivibart as well as further clinical studies. “Pemgarda is the first authorized monoclonal antibody from our proprietary platform approach,” said Invivvyd CEO Dave Hering in statement. We are committed to ongoing process improvement while working with global regulatory agencies with the aim to increase the speed and efficiency of new mAb candidate development even further. Additionally, we are planning to explore the protective clinical benefits of mAb prophylaxis for symptomatic COVID-19 disease in future studies.”1


1. 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 March 23, 2024.
2. Parkinson J. EUA Requested for Monoclonal Antibody For Prevention of COVID-19 in Immunocompromised Adults and Teens. Contagion. January 3, 2024. Accessed March 23, 2024.

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