Pemivibart Shows Safety, Prevents COVID-19 in CLL Subset in Phase 3 CANOPY Trial

A phase 3 trial demonstrated favorable safety and efficacy of pemivibart for prevention of SARS-CoV-2 infection in a small subset of patients with chronic lymphocytic leukemia (CLL).¹

The abstract, published in supplements of both Transplantation and Cellular Therapy and Journal of Hematology Oncology Pharmacy,^1,2 used data from the CANOPY trial (NCT06039449) to assess the response of patients with CLL to pemigatinib, considering that they are likely to be immunocompromised and less responsive to the COVID-19 vaccine. The CANOPY trial, overall, assessed the safety and efficacy of pemivibart, or VYD222, a recombinant monoclonal IgG1λ antibody that targets the SARS-CoV-2 spike protein receptor binding domain, thus inhibiting the virus from attaching to human angiotensin-converting enzyme 2 receptors on the host cell. Pemivibart is not FDA approved for any use. However, it was granted emergency use authorization (EUA) by the FDA under the brand name Pemgarda (Invivyd) for pre-exposure prevention of COVID-19 in adult and adolescent patients 12 years and older based on findings from the CANOPY trial.³

Under the EUA, issued on March 22, 2024, pemivibart is cleared for pre-exposure prophylaxis of COVID-19 in patients who are not currently infected nor have been exposed to someone infected with COVID-19 and those who have moderate to severe immune compromise due to a medical condition or receipt of immunosuppressive medications or treatments, making them less likely to be fully protected by the COVID-19 vaccine.³

In 2025, Invivyd’s bid to expand the EUA was denied by the FDA. Sources cite the FDA’s stringent requirement for antibody activity; thus, it cannot be used for postexposure prevention or treating an active infection.⁴

In cohort A of the CANOPY trial, patients received 4500 mg of pemivibart intravenously on day 1 and received a second dose at the month 3 visit. The primary outcomes, safety and tolerability, were assessed as the incidence of treatment-emergent adverse events (TEAEs). An exploratory end point also evaluated the incidence of symptomatic COVID-19 confirmed by reverse transcription-polymerase chain reaction (RT-PCR), including COVID-19–related hospitalization and all-cause mortality.

All participants were vaccinated for COVID-19 prior to enrollment, with a median of 6 vaccinations. Of the 306 immunocompromised patients in cohort A, 29 (9.5%) were included in the CLL subset. The median age was 66 years; 15 (51.7%) were female, and 28 (96.6%) were non-Hispanic White.

Nine participants (31%) were receiving antineoplastic agents, including venetoclax (n = 3), acalabrutinib (n = 2), and ibrutinib (n = 2). Eighteen (62.1%) participants experienced TEAEs, although none of them were considered serious and none of them resulted in study drug discontinuation. However, 5 of 29 (17.2%) patients with CLL experienced mild adverse events considered related to pemivibart. Of them, 4 participants experienced possible symptoms of an infusion-related reaction within 24 hours of dosing. Additionally, there was 1 event of tachycardia and 1 event of fatigue after dose 1, and 1 event of nausea and 1 event of headache after dose 2.

The composite incidence of RT-PCR–confirmed symptomatic COVID-19 was 3.7% through day 180, none of whom were in the CLL subset. Furthermore, none of the patients in the CLL subset developed COVID-19 in the 6 months following administration of pemivibart.

This abstract was limited, as the subset population of patients was small, making generalizability difficult. Additionally, there was no control group within the subset, and the follow-up was relatively short, limiting long-term observation on safety, tolerability, and efficacy.

References

1. Hawn P, Narayan K, Phelan AM, Li Y, Gupta D, Wilfret D, Holmes A. A phase 3 study to evaluate efficacy and safety of pemivibart, an IgG1 monoclonal antibody for prevention of COVID-19 (CANOPY): subset analysis of participants with chronic lymphocytic leukemia. Transplant Cell Ther. 2025;31(suppl 2):S512. doi:10.1016/j.jtct.2025.01.814

2. Beaulac K. Phase 3 study to evaluate efficacy and safety of pemivibart, an IgG1 monoclonal antibody, for the prevention of COVID-19 (CANOPY): subset analysis of participants with chronic lymphocytic leukemia. J Hematol Oncol Pharm. 2026;16(Spec):CR08. https://www.jhoponline.com/issue-archive/2026-issues/march-2026-vol-16-special-feature/phase-3-study-to-evaluate-efficacy-and-safety-of-pemivibart-an-igg1-monoclonal-antibody-for-the-prevention-of-covid-19-canopy

3. Emergency use authorization (EUA) for pemivibart. FDA. July 21, 2025. Accessed April 7, 2026. https://www.fda.gov/media/187951/download

4. Samorodnitsky D. FDA shoots down Invivyd’s bid to expand EUA for COVID-19 antibody. BioSpace. February 24, 2025. Accessed April 7, 2026. https://www.biospace.com/fda/fda-shoots-down-invivyds-bid-to-expand-eua-for-covid-19-antibody