WASHINGTON – The recombinant fusion protein atacicept, which targets B-cell stimulating factors BLyS and APRIL, had a favorable safety profile and showed some evidence of efficacy in systemic lupus erythematosus patients – particularly those with high disease activity and serologically active disease – in the randomized, phase IIb ADDRESS II study.
Although the primary endpoint of the study – percentage of patients achieving SLE responder index-4 (SRI-4) response at 24 weeks – was not met, a reduction in both disease activity and severe flares was observed in patients in the multicenter study who received atacicept vs. placebo, Joan T. Merrill, MD, of the Oklahoma Medical Research Foundation, Oklahoma City, reported in a late-breaking poster at the annual meeting of the American College of Rheumatology.
Dr. Joan T. Merrill
However, in a prespecified sensitivity analysis using study day 1 rather than screening visit as baseline, significantly more patients in the atacicept groups achieved SRI-4 response at week 24. For example, compared with a 41% SRI-4 response rate in the placebo group, the rate was 55.9% for the 75-mg atacicept group (odds ratio, 1.88) and 55.8% for the 150-mg atacicept group (odds ratio, 1.96), Dr. Merrill said.
Further, enhanced improvements in both SRI-4 and SRI-6 (a composite measure including reduction of at least 6 points on the SLEDAI-2K) were seen in the atacicept groups vs. the placebo group in 158 patients with high disease activity (defined as SLEDAI-2K of 10 or greater), in 84 patients with serologically active disease (those with dsDNA antibody-positive disease and low complement), and in 69 patients with both.
For example, SRI-4 response rates in patients with high disease activity were significantly greater with atacicept 150 mg vs. placebo at week 24 (62.7% vs. 42.3%; odds ratio, 2.43), and the corresponding SRI-6 rates were 54.9% vs. 28.8% with an odds ratio of 3.30.
The SRI-4 rates at week 24 in those with both high disease activity and serologically active disease who received 150 mg atacicept vs. placebo were 65% vs. 25% (odds ratio, 7.48), and the SRI-6 rates in those patients were 55% vs. 16.7% (odds ratio, 7.13).
In patients with high disease activity, severe flare was reduced with both the 75-mg and 150-mg doses of atacicept, Dr. Merrill said, noting that in the intent-to-treat population, BILAG A flare was significantly reduced with atacicept 75 mg vs. placebo, and severe flares (as measured with the SLEDAI flare index) was reduced with atacicept 150 mg.
Atacicept was associated with increased serum complement C3/C4, and with decreased IgG, IgM, IgA, and anti-dsDNA antibodies over time, she said.
Treatment-emergent adverse events occurred in similar percentages of patients in the groups (71% with placebo, 81.4% with 75 mg atacicept, and 80.8% with 150 mg atacicept). Serious treatment-emergent adverse events occurred in 11%, 8.8%, and 5.8%, respectively.
In a press statement, Dr. Merrill said the results are impressive, particularly for a small, 24-week study.
“If confirmed in future studies, this could hold exciting possibilities for our patients,” she said.
ADDRESS II was sponsored by EMD Serono. Dr. Merrill reported financial relationships with Anthera Pharmaceuticals and Lilly. Other authors reported financial relationships with EMD Serono/Merck Serono.