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Atacicept is a dual anti-BAFF/APRIL fusion protein currently in clinical development for treatment of IgA nephropathy (IgAN). Better understanding vaccine response and immunity with atacicept, especially to COVID-19, may help assess atacicept’s benefit risk profile. Atacicept has been studied in IgAN in the Phase 2a JANUS study, which measured tetanus and diphtheria vaccine titers up to 72 weeks, and the Phase 2b ORIGIN study, where impact of atacicept on COVID-19 infection rates and severity could be assessed.
JANUS and ORIGIN were double-blind placebo-controlled studies that enrolled adults with biopsy-proven IgAN and UPCR >0.75 g/g who were on stable doses of renin-angiotensin system inhibitors. Participants were randomized 1:1:1 to placebo, atacicept 25, or 75 mg SC once weekly for 72 weeks in JANUS (n=16) and 2:1:2:2 to placebo, atacicept 25, 75, or 150 mg SC once weekly for 36 weeks in ORIGIN (n=116). In JANUS, tetanus and diphtheria titers were measured at 1, 48 and 72 weeks in addition to safety assessments. In ORIGIN, safety data on infections were analyzed by treatment arm up to 36 weeks.
The JANUS population was 50% male with baseline median age 44; the ORIGIN population was 59% male with median age 37. No JANUS participants changed from protective to nonprotective status for diphtheria or tetanus toxin; overall infections were balanced between atacicept and placebo. ORIGIN participants across atacicept and placebo arms had similar rates of overall and COVID-19 infections (Table). All participants with COVID-19 had ≥1 COVID-19 vaccine dose prior to infection. No COVID-19 infection was serious; most were mild. Median duration of COVID-19 infection was 7.5 (IQR 7, 9) days. There were no permanent discontinuations, although some COVID-19 infections led to temporary study drug interruption. No COVID-19 infection was reported as study drug related.
Atacicept treatment was associated with continued protective immunity to tetanus and diphtheria in the Phase 2a JANUS study. In the Phase 2a JANUS and Phase 2b ORIGIN studies, infections were balanced between atacicept and placebo, with no increase in incidence or severity of COVID-19 infections in the ORIGIN study.
This abstract was also submitted for ASN Kidney Week 2023. By submitting the abstract to WCN’24, abstract authors declare that re-submitting the abstract is permitted by the organizers of the previous meeting.