Integrated Safety Profile of Atacicept from All Clinical Studies to Date

Background We conducted an integrated analysis of pooled safety data from all 17 atacicept clinical studies across multiple indications to date, to characterize the safety profile of atacicept. Methods Analyses were based on 3 pooled datasets: double-blind placebo-controlled (DBPC) set (n=1568; key endpoint: treatment-emergent AEs [TEAEs]); SLE set (n=761; key endpoint: IgG change and serious infection rates); and full analysis set (n=1845; key endpoint: exposure-adjusted mortality). Results Of 1568 patients in the DBPC set, 30.8% received placebo, 8.2% atacicept 25 mg, 24.5% atacicept 75 mg and 36.5% atacicept 150 mg. Overall, baseline characteristics were balanced across treatment arms. Treatment exposure was similar with placebo and atacicept 75 and 150 mg (278.3, 225.0 and 286.7 patient-years, respectively), but was lower with atacicept 25 mg (51.5 patient-years). Exposure-adjusted TEAE rates were generally higher with atacicept vs placebo, with no consistent association between atacicept dose and cardiac arrhythmias, serious and severe infections or injection site reactions (table 1). Serious infection and serious TEAE rates were similar between atacicept and placebo. TEAE-related discontinuation rates were higher with atacicept vs placebo (16.1 vs 10.9 per 100 patient-years). In the SLE set, there was no association between reduced IgG levels and increased infection rates. Across all studies (full analysis set), 11 patients died during treatment (10 atacicept [0.5%], 1 placebo [0.1%]). Infection-related deaths in the DBPC set are shown in the table 1. Exposure-adjusted mortality rates per 100 patient-years were 3.60 (95% CI: 0.90–14.38) with atacicept 25 mg, 0.34 (95% CI: 0.05–2.43) with 75 mg, 1.18 (95% CI: 0.49–2.82) with 150 mg, and 0.44 (95% CI: 0.06–3.12) with placebo. Conclusions Results from this pooled analysis clarify the benefit-risk relationship for atacicept, which is being further evaluated in additional clinical studies in IgA nephropathy and SLE. Funding Source(s): Merck KGaA, Darmstadt, Germany