Treatment with 150 mg atacicept significantly improves outcomes in systemic lupus erythematosus (SLE) patients with high disease activity, data from a Phase 2b clinical trial show.
The results of the trial were presented recently at the 2018 SLEuro Annual Meeting in Dusseldorf, Germany in a poster titled “SRI response, attainment of low disease activity and safety in patients with systemic lupus treated with atacicept in a Phase IIb study (ADDRESS II).”
Atacicept, developed by EMD Serono, is an investigational inhibitor of two signalling molecules — BLyS and APRIL — linked to disease activity and autoantibody production in SLE.
The ADDRESS II study (NCT01972568) was a multi-center, double-blind study set up to investigate the effectiveness and safety of investigational atacicept in patients with SLE.
The study enrolled 306 SLE patients receiving standard therapy who were randomized to receive one of two atacicept doses — 75 or 150 mg — or a placebo for 24 weeks. The therapy and placebo were delivered in once-a-week subcutaneous injections (under the skin).
A subset of the study participants (158) had high disease activity, identified as a SLE disease activity index 2000 (SLEDAI-2K) score of 10 or higher at baseline.
The study’s primary goal was to assess the percentage of SLE patients with a decrease in disease activity, measured as a reduction of four or more points in the SLE Responder Index (SRI-4) at the end of the study (week 24).
Additional study goals included SRI-5 through SRI-8 response, and achieving low disease activity.
In 2016, EMD Serono said the ADDRESS II trial failed to meet its primary endpoint, defined as the proportion of patients achieving a clinical response, using screening visit as baseline.
However, another analysis using the first day of treatment as baseline revealed that a significantly higher proportion of patients treated with atacicept achieved SRI-4 response at week 24.
Looking specifically to patients with high disease activity, treatment with the highest dose of atacicept (150 mg) led to significant improvements in SRI-4, -5, -6, -7 and -8 response rates, and resulted in more patients achieving low disease activity compared to placebo.
In this patient population, the SRI-4 response was 62.7% atacicept-treated patients, compared to 42.3% in the placebo group.
The findings confirm early indications of the therapy’s effectiveness in lupus patients.
Overall, “atacicept showed evidence of efficacy in SLE with a dose-dependent reduction of SLE disease activity in patients with HAD [high disease activity],” the study concluded.