Results from a 24-week Phase 2b study show that atacicept treatment is safe and reduces disease activity and severe flare in systemic lupus erythematosus (SLE) patients, particularly in those with high disease activity or serologically active disease.
Results of the ADDRESS II trial (NCT01972568) were published in the study, “Efficacy and Safety of Atacicept in Patients with Systemic Lupus Erythematosus: Results of a 24-week Randomized, Placebo-Controlled, Phase IIb Study,” in the journal Arthritis and Rheumatology.
Lupus disease activity and autoantibody production are associated with elevated levels of the cytokines B lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL).
Benlysta (belimumab), a BLyS inhibitor, is already approved for treatment of lupus patients. But now, EMD Serono sought to assess the safety and effectiveness of the dual APRIL and BLyS inhibitor atacicept in this patient population.
The ADDRESS II Phase 2b trial was a randomized, double-blind, placebo-controlled, multicenter study. It included 306 patients receiving standard therapy, who were randomized to receive either 75 mg or 150 mg of atacicept, or a placebo, once a week. All patients had active, autoantibody-positive lupus.
The study reported findings at the end of a 24-week treatment period. Disease activity at screening or at day 1 was used as the baseline, while the SLE responder index-4 (SRI-4), a measure of disease activity, at week 24 was used as the primary endpoint for the study.
Although the primary endpoint, or main goal of the study, was not met at week 24, trends in treatment responses were observed from week 16. At week 24, there was an overall trend toward improved SRI-4 in patients treated with 75 mg of atacicept (57.8%) and 150 mg of atacicept (53.8%), compared to the placebo (44%). More robust effects were observed when day 1 was used as a baseline, or study starting point.
Statistically significant improvements in SRI-4 and SRI-6 (which requires a greater response) were observed in subgroups of patients who had serological active disease or high disease activity (HDA) at baseline.
Atacicept also reduced the levels of serum immunoglobulins and anti-dsDNA antibodies, and increased complement levels, confirming its biological activity. The effects were greater than those observed with drugs targeting BLyS alone.
There were no increases in the frequency of adverse effects (AEs) or serious infections, and no cases were reported of severe hypogammaglobulinemia (low levels of antibodies in the blood) or death, indicating that atacicept had an acceptable safety profile.
The authors concluded that “although this phase IIb study did not meet its primary endpoint, there was robust discrimination between atacicept and placebo in multiple endpoints, particularly in subpopulations with serologic activity and/or HDA. There was no increase in the risk of serious AEs, including serious infections, in patients treated with atacicept. These results support further clinical evaluation of atacicept in SLE.”