What is the available literature for Pemivibart (Pemgarda) for COVID-19?

Comment by InpharmD Researcher

There is currently a lack of published literature evaluating the use of pemivibart (Pemgarda). Pemivibart, a SARS-CoV-2 spike protein-directed attachment inhibitor, is available under an Emergency Use Authorization (EUA) issued by the FDA for pre-exposure prophylaxis of COVID-19 in adults and adolescents 12 years of age and older who are not currently infected with SARS-CoV-2 but have moderate-to-severe immune compromise and are unlikely to mount an adequate immune response to COVID-19 vaccination. The ongoing phase 3 CANOPY trial for pemivibart utilized an immunobridging approach with neutralizing antibody (sVNA) titers and clinical efficacy data that was demonstrated in the previous EVADE clinical trial for the parent monoclonal antibody of pemivibart (adintrevimab). Interim results from CANOPY appear to support the efficacy and safety of pemivibart for pre-exposure prophylaxis against the JN.1 SARS-CoV-2 variant based on sVNA titers in adults who are moderately-to-severely immunocompromised and adults who are not immunocompromised. It should be noted that pemivibart is not FDA-approved for any use, including pre-exposure prophylaxis of COVID-19, as it is only authorized for use under the current EUA.

Background

On March 22, 2024, Invivyd Inc. announced interim exploratory COVID-19 clinical event data for pemivibart, an investigational, monoclonal antibody (mAb) in development for the pre-exposure prophylaxis of COVID-19. The ongoing CANOPY phase 3 trial, with an estimated completion date of November 2024, assessed pemivibart’s safety, tolerability, and immunobridging to historical data from a previous phase 2/3 trial of adintrevimab for preventing symptomatic COVID-19 (EVADE trial). Leveraging the established correlation between serum virus-neutralizing antibody (sVNA) titer and clinical effectiveness demonstrated in the earlier EVADE clinical trial, an immunobridging strategy was employed. At the time of analysis, the primary SARS-Cov-2 variant circulating in the U.S. (JN.1) was chosen for evaluation as the key variant in the primary immunobridging endpoint assessment. [1], [2], [3]

In CANOPY trial, cohort A includes adults with moderate-to-severe immune compromise (n= 306) in a single-arm, open-label trial, while cohort B includes adults at risk of acquiring SARS-CoV-2 through regular unmasked face-to-face interactions in indoor settings, randomized 2:1 to pemivibart (n= 317) or placebo (n= 162) via intravenous infusion. In December 2023, the company disclosed a potential early signal of clinical protection from symptomatic COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR). Invivyd provides updates on confirmed symptomatic COVID-19 cases through Day 90. However, additional COVID-19 cases have emerged in cohorts A and B after Day 90. These cases will be analyzed on Day 190 and will be presented at a later time. For cohort B, the proportion of participants with RT-PCR-confirmed symptomatic COVID-19 through Day 90 is as follows: pemivibart 1/314 (0.3%), and placebo 8/159 (5%). As for cohort A involving those with moderate-to-severe immune compromise, the proportion of subjects with confirmed symptomatic COVID-10 in the pemivibart group is 1% (3/298). [1], [2], [3]

In cohort A, the calculated Day 28 sVNA titer for pemivibart against JN.1 was 7,365 (90% confidence interval [CI] 7148 to 7589), while the ratio between this Day 28 titer for pemivibart against JN.1 and a Day 28 adintrevimab reference titer of 8,944 was 0.82 (90% confidence interval [CI] 0.80 to 0.85), indicating the establishment of immunobridging in the CANOPY clinical trial. In terms of safety data, anaphylaxis occurred in 4 out of 623 (0.6%) CANOPY participants, all in cohort A. Two experienced it during the first infusion and were treated with diphenhydramine; the other two had it during the second infusion (both incidents were life-threatening, requiring treatment with diphenhydramine, epinephrine, and additional medication). All reactions led to permanent discontinuation of pemivibart. [1], [2], [3]

References:

[1] Invivyd. Press Release. Invivyd announces interim exploratory data on VYD222 from ongoing canopy clinical trial. Published March 22, 2024. Accessed March 27, 2024.
[2] Invivyd. Press release. Invivyd announces FDA authorization for emergency use of pemgarda™ (formerly VYD222) for pre-exposure prophylaxis (prep) of COVID-19. Published March 22, 2024. Accessed March 27, 2024.
[3] ClinicalTrials.gov. A Study to Investigate the Prevention of COVID-19 with VYD222 in Adults With Immune Compromise and in Participants Aged 12 Years or Older Who Are at Risk of Exposure to SARS-CoV-2. Updated January 18, 2024. Accessed March 27, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06039449
Relevant Prescribing Information

EMERGENCY USE AUTHORIZATION (EUA) FOR PEMGARDA:
The U.S. FDA has issued an EUA for the emergency use of the unapproved product PEMGARDA (pemivibart), a SARS-CoV-2 spike protein-directed attachment inhibitor, for the pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in adults and adolescents (12 years of age and older weighing at least 40 kg):

- Who are not currently infected with SARS-CoV-2 and who have not had a known recent exposure to an individual infected with SARS-CoV-2, and
- Who have moderate-to-severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments and are unlikely to mount an adequate immune response to COVID-19 vaccination.

PEMGARDA has been authorized by FDA for the emergency use described above. PEMGARDA is not FDA-approved for any use, including use for pre-exposure prophylaxis of COVID-19. [4]

References:

[4] Pemgarda (pemivibart). Emergency Use Authorization. Invivyd; 2024.