Lupus Patients with Highly Active Disease Responded Well to Atacicept in Short- and Long-term, Phase 2 Trial Shows

Systemic lupus erythematosus (SLE) patients with highly active disease responded well to treatment with atacicept at 150 mg each week — especially those on continuous treatment for about one year, results from a Phase 2b study and its long-term extension show.

The findings were revealed at the American College of Rheumatology (ACR) 2018 Annual Meeting held in Chicago last month. The study was titled “Attainment of Low Disease Activity and Remission in SLE Patients Who Started with High Disease Activity in the Atacicept Phase IIb Address II Study and Its Long-Term Extension.”

Atacicept, being developed by EMD Serono (known as Merck KGaA outside North America), is an investigational inhibitor of two signaling molecules — BLyS and APRIL — linked to disease activity and autoantibody production in SLE, or lupus, patients.

The ADDRESS II clinical trial (NCT01972568) randomly assigned 306 patient to under-the-skin weekly injections of either 150 mg or 75 mg atacicept, or a placebo, for 24 weeks.

A subgroup of 158 patients entered the study with evidence of high disease activity (called a baseline measure) – defined by a SLE Disease Activity Index 2000 (SLEDAI-2K) of 10 or higher.

An open-label extension followed, with patients under treatment continuing at their assigned dose for another 24 weeks, and placebo group patients moving to atacicept at 150 mg.

The initial study’s main goal was to assess how many and how well patients lowered their disease activity scores — measured as a reduction or four or more points in the SLE Responder Index (SRI) at 24 weeks.

Researchers reported in April that a significantly higher proportion of patients given atacicept achieved a clinical response — with day one of treatment as the baseline measure — than did those on placebo. Patients with highly active disease also showed significant improvement by this baseline compared to placebo, showing benefit across a range of SRI scores (SRI-4, -5, -6, -7 and -8) and fewer experiencing lupus flares over the study’s 24 weeks.

In this study, researchers looked specifically at outcomes in the 158 patients with highly active disease at both 24 and 48 weeks, by assessing SRI-6 responses and additional measures of disease activity.

Measures used included low disease activity, or LDA (defined as SLEDAI-2K score of 2 or less); lupus low disease activity state, or LLDAS (defined as SLEDAI-2K score of 4 or lower without major organ activity, a prednisone dose of 7.5 mg/day or less, and a stable maintenance dose of immunosuppressants); and remission (defined as a 0 clinical SLEDAI-2K score and a prednisone dose of 5 mg/day or less).

Data showed that after the initial 24 weeks of treatment, 42.4% of these patients had achieved SRI-6, 23.4% showed LDA, 15.8% LLDAS, and 10.8% were in remission.

Their outcomes continued to improve in the trial’s extension phase, researchers reported. After 48 weeks of treatment, 52.5% reached SRI-6, 26.6% LDA, 19.0% LLDAS, and 10.8% were in remission. Among the 86 patients whose SLE Responder Index score dropped by six or more points, nearly half — 49.4% — had attained LDA, and more than one third — 34.9% — had reached LLDAS. Among these patients, 20.5% were in remission.

Those treated weekly with atacicept at 150 mg for the entire 48-week study period had better outcomes than those with high disease activity given the 75 mg dose or those who switched from placebo to active treatment for 24 weeks, the study also showed.

“ADDRESS II pts [patients] with HDA at Screening receiving atacicept 150 mg were more likely to attain LDA, LLDAS and remission at Week 48 than those treated with atacicept 75 mg or PBO/atacicept 150 mg,” its researchers wrote.

They also stated that its findings “support future studies of atacicept in SLE.”

The scientists also suggested that LDA and LLDAS might be better endpoints for clinical trials in lupus patients, as they consider them more stringent measures of disease activity than SLE Response Index measures.