Background Atacicept targets B-cell stimulating factors BLyS and APRIL, and has shown evidence of clinical response in SLE.

Objectives Exploration of atacicept efficacy and safety in a pre-defined subpopulation of SLE patients with high disease activity (HDA, SLEDAI-2K ≥10 at Screening) in the phase IIb ADDRESS II study (NCT01972568).

Methods Autoantibody positive patients on standard of care therapy were randomized 1:1:1 to double-blind weekly SC injections of atacicept 75 or 150 mg or placebo (PBO) for 24 weeks. Analyses of the HDA subpopulation are now reported.

Results 52% of the ITT population had HDA (n=158: 52 PBO; 55 atacicept 75 mg; 51 atacicept 150 mg). 92% were female, 67% were white, and baseline characteristics were balanced between groups. At week 24 (Table 1; Figure 1), the proportion of SLE Responder Index (SRI)-4 (p<0.05) and SRI-6 (p<0.005) responses was greater with atacicept 150 mg vs PBO. BICLA response rate was higher with both doses (p<0.05). More patients achieved SLEDAI-2K ≤2 with atacicept 150 mg vs PBO (p<0.01). Time to severe and moderate-severe flare was significantly reduced at both atacicept doses vs PBO (p<0.05). Patients in the quartile with the largest decline in serum IgG had the highest SRI-6 response rates (Table 2). Treatment-emergent adverse event (TEAE) rates were similar between groups (PBO 71.2%; 75 mg 78.2%; 150 mg 74.5%). Serious/severe infections were not increased with atacicept 150 mg (PBO 9.6%; 75 mg 10.9%; 150 mg 0%). There were no patient deaths.

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Conclusions In SLE patients with HDA, Atacicept 150 mg demonstrated significant clinical responses and an acceptable safety profile.

Acknowledgements The study was sponsored by EMD Serono Research & Development Institute Inc., USA (a business of Merck KGaA, Germany). Medical writing support was provided by Bioscript Science, UK, and funded by Merck KGaA.

Disclosure of Interest J. Merrill Consultant for: received consulting fees from Anthera Pharmaceuticals, Lilly, EMD Serono, GlaxoSmithKline and Biogen, D. Wallace Consultant for: received consulting fees from EMD Serono, A. Kao Employee of: EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA, C. Vazquez Mateo Employee of: EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA, P. Fraser Employee of: EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA, P. Chang Employee of: EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA, D. Isenberg Consultant for: received consulting fees from EMD Serono