By Gina Shaw
The monoclonal antibody pemivibart (Pemgarda, Invivyd) is well tolerated and appears effective in preventing symptomatic COVID-19 infection among patients with chronic lymphocytic leukemia (CLL), who can be severely immunocompromised, according to a study reported at MAD-ID 2025, in Orlando, Fla. (abstract 96E).
Authorized by the FDA under an emergency use authorization, pemivibart is indicated for certain patients with medical conditions or receiving immunosuppressive treatments leading to moderate to severe immunodeficiency, who are unlikely to mount an adequate immune response to COVID-19 vaccination.
“People with CLL are notably immunocompromised and at risk for opportunistic infections such as COVID-19 for a long-lasting period, without the opportunities for immune reconstitution seen in some other clinical indications for COVID-19 pre-exposure prophylaxis,” said Kira Beaulac, PharmD, a medical science liaison with Invivyd, who presented the study data of a subset analysis from the single-arm open-label phase of CANOPY, a phase 3 study to evaluate the efficacy and safety of pemivibart for prevention of COVID-19.
The CANOPY subset analysis included 29 CLL patients, 9.5% of the larger open-label Cohort A’s 306 immunocompromised participants. Median (range) age was 66 (39-83) years; 15 (51.7%) were female and 28 (96.6%) white. Nine participants (31.0%) were receiving antineoplastic agents, including three on venetoclax (Venclexta, AbbVie) and two each on acalabrutinib (Calquence, Astra Zeneca) and ibrutinib (Imbruvica, Pharmacyclics and Janssen Biotech). A significant number had other comorbidities, including cardiac disease (41.4%), obesity (24.1%), diabetes (13.8%) and chronic lung disease (17.2%).
Patients received 4,500 mg IV of pemivibart on day 1 and a second dose at the month 3 visit. Primary end points included safety and tolerability, as measured by incidence of treatment-emergent adverse events (TEAEs), including serious AEs. An exploratory end point evaluated the incidence of confirmed symptomatic COVID-19, including COVID-related hospitalization and all-cause mortality.
Twenty-two of 29 participants (76%) experienced TEAEs; none were considered serious, and none caused study drug discontinuation. Five (17.2%) experienced AEs considered related to pemivibart, including tachycardia and fatigue, nausea, and headache; all were considered mild. “No cases of confirmed symptomatic COVID-19 were reported in this subset of patients through month 6 of the analysis,” Dr. Beaulac said.
Many prior studies of agents for COVID-19 prophylaxis were conducted earlier in the course of the pandemic, with prior variants. “This study was conducted from 2023 into 2024, under a contemporary variant landscape with widespread availability of vaccines as well,” Dr. Beaulac noted. “Pemivibart is specifically engineered to the binding site where the human ACE2 [angiotensin-converting enzyme 2 ] receptor meets the COVID-19 spike protein, a highly preserved epitope that is not under selective pressure to mutate.”
While the drug was only dosed twice (at baseline and a redosing at month 3), study participants were followed through month 12. During the follow-up period, six participants developed COVID-19, with a median time of approximately 7.5 months from the last dose to onset of symptoms. “These infections were all mild to moderate in nature,” Dr. Beaulac said. “This highlights the importance of dosing every three months among these highly immunocompromised patients, because once you are in the post-dosing phase, you do run the risk of developing an infection.”
The full interim results of CANOPY were published in Clinical Infectious Diseases (2025 May 25. https://doi.org/10.1093/cid/ciaf265).
Dr. Beaulack reported no relevant financial disclosures outside her employment.
