Background/Purpose:  Atacicept, a recombinant fusion protein, targets both BLyS (B lymphocyte stimulator) and APRIL (a proliferation-inducing ligand), B cell activating factors involved in the pathogenesis of B cell-driven autoimmunity. This study aims to summarize safety data from double-blind, placebo-controlled, phase II studies of atacicept in autoimmune diseases.

Methods: Safety data were pooled from 7 studies of atacicept 25, 75 or 150 mg in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), optic neuritis (ON), and lupus nephritis (LN).

Results: A total of 1262 subjects were included (RA, n=513 [41%]; SLE, n=455 [36%]; MS, n=254 (20%); ON, n=34 (3%); LN, n=6 [1%]); 30% received placebo (PBO), and 10.2%, 22%, and 37.1% received atacicept 25, 75, or 150 mg, respectively. Treatment-emergent adverse events (TEAEs) were similar across groups (atacicept: 75.2%, 77.7% and 75.6% with 25 mg, 75 mg and 150 mg; PBO: 72.3%) (Table 1). Infections/infestations were the most frequent TEAE (atacicept: 33.3%, 47.9% and 49.1% with 25 mg, 75 mg and 150 mg; PBO: 43.1%) and were reported in subjects with SLE (62.4%, 60.4% with 75 mg and 150 mg; PBO: 55.2%), RA (34.8%, 19.4%, 37.4% with 25 mg, 75 mg and 150 mg; PBO: 32.7%), MS/ON (31.7%, 39.7%, 62.2% with 25 mg, 75 mg and 150 mg; PBO: 40.0%), and LN (75% with 150 mg; PBO: 0%). Pneumonia was the most common serious TEAE (atacicept: 0%, 2.1% and 1.1% with 25 mg, 75 mg and 150 mg; PBO: 1.0%) and the most common severe TEAE (atacicept: 0%, 1.1%, 0.9% with 25 mg, 75 mg and 150 mg; PBO: 0.5%). SLE subjects accounted for the majority of serious and severe pneumonia cases (80% and 67%, respectively). Six treatment-emergent deaths were reported (n=3, 2, 1 in RA, SLE, MS), atacicept n = 1, 1, and 3 with 25 mg, 75 mg and 150 mg, PBO n=1; mortality rate/100 subject-years was atacicept 1.05 vs. PBO 0.43. Herpes zoster (HZ) infections were mild/moderate and infrequent (1.3%) but occurred more commonly with atacicept (1.6% vs 0.8%, with atacicept [n=14] vs PBO [n=3]). All 3 PBO-treated subjects and 57% atacicept-treated subjects with HZ had SLE. The proportion of subjects experiencing HZ by dose was: 25 mg (0.8% overall); 75 mg (1.8% overall; 2.5% SLE); and 150 mg (1.7% overall; 2.8% SLE). No serious HZ infections were reported with atacicept.

Conclusion: TEAE rates were similar between atacicept and PBO groups, with infections the most commonly reported. Subjects with SLE appeared more likely to develop infection-related TEAE (ie, HZ) and serious/severe TEAE (ie, pneumonia). Numbers of deaths were low and were observed across the diseases. The safety profile of atacicept appears to be similar to other B cell-targeted therapies, and is being further evaluated in clinical studies of SLE patients. Table 1. Overall analysis set

*Includes myocardial infarction. TEAE, treatment-emergent adverse event; PML, progressive multifocal leukoencephalopathy

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/atacicept-integrated-safety-profile-from-phase-ii-randomized-placebo-controlled-studies-in-autoimmune-diseases/