Presenting Author: Kirthana Beaulac, PharmD, Invivyd, New Haven, CT
BACKGROUND: Pemivibart (VYD222) is a recombinant human monoclonal IgG1λ antibody that targets the SARS-CoV-2 spike protein receptor binding domain, thereby inhibiting virus attachment to the human angiotensin converting enzyme 2 receptor on host cells. The FDA issued pemivibart an emergency use authorization (EUA) for pre-exposure prophylaxis of COVID-19 in certain adults and adolescents with moderate-to-severe immune compromise in March 2024. Data supporting this EUA was from CANOPY (NCT06039449), a phase 3 study that evaluated the efficacy and safety of pemivibart for the prevention of COVID-19.
OBJECTIVE: To describe a subset of participants in the single-arm, open-label cohort A of CANOPY who were considered to have significant immune compromise because of chronic lymphocytic leukemia (CLL).
METHODS: All cohort A participants received 4500 mg intravenously of pemivibart on day 1 and received a second dose at the 3-month visit. Primary objectives: (1) Safety and tolerability of pemivibart, which were assessed as the incidence of treatment-emergent adverse events (TEAEs), including serious AEs, (2) Evaluation of protection against symptomatic COVID-19 based on serum viral neutralizing antibody titers against SARS-CoV-2 after receiving pemivibart. An exploratory end point evaluated the incidence of reverse transcription polymerase chain reaction (RT-PCR)-confirmed symptomatic COVID-19, including COVID-related hospitalization and all-cause mortality.
RESULTS: CANOPY enrollment began in September 2023 when the XBB-related and JN.1 variants of COVID were dominant. A total of 306 immunocompromised participants were enrolled in cohort A. Of those, 29 (9.5%) were included in the CLL subset, of whom the median age was 66 years (range, 39-83 years), 15 (51.7%) were female, and 28 (96.6%) were White. In all, 9 (31%) participants were receiving antineoplastic agents, including venetoclax (n=3), acalabrutinib (n=2), and ibrutinib (n=2). All participants were vaccinated for COVID-19 before enrollment, having received a median of 6 vaccinations (range, 2-7 vaccinations). A total of 18 (62.1%) participants had TEAEs; none of the TEAEs were considered serious or caused study drug discontinuation. Of 29 participants, 5 (17.2%) had AEs that were related to pemivibart, all of which were considered mild. Of these 5 patients, 4 participants had possible symptoms of an infusion-related reaction within 24 hours of dosing: 1 event each of tachycardia and fatigue after dose 1, and 1 event each of nausea and headache after dose 2. Among all cohort A–enrolled participants, the composite incidence of RT-PCR–confirmed symptomatic COVID-19 was 3.7% through day 180. None of the participants within the CLL subset were among these RT-PCR–confirmed symptomatic COVID-19 cases.
CONCLUSION: Pemivibart was well tolerated in a subset of adults with CLL. None of the study patients had COVID-19 in the 6 months after the administration of pemivibart.