Xencor announced top-line results from its Phase 2 clinical trial testing the candidate antibody therapy XmAb5871 for the treatment of systemic lupus erythematosus (SLE). The antibody seems to help control or reduce lupus disease activity after patients have been given a brief course of anti-inflammatory steroid medications.
XmAb5871 is a monoclonal antibody that targets both CD19 and the FcγRIIb receptor, two molecules present at the surface of B-cells — critical immune cells that malfunction in lupus. By targeting these molecules, the antibody blocks B-cell activation, turning down the autoimmune response.
XmAb5871 inhibits B-cell function without destroying these cells, which enables the natural immune system to function once treatment is no longer needed. This ability differentiates it from other B-cell targeting therapies and has potential for treating many autoimmune diseases, Xencor states.
In 2016, Xencor began a randomized, double-blind, placebo-controlled Phase 2 study (NCT02725515) to determine the ability of XmAb5871 to keep lupus disease activity low after a short steroid treatment.
The study enrolled 104 patients with moderate to severe, non-organ-threatening SLE across 20 centers in the United States.
Patients withdrew immunosuppressive medication (except antimalarials or up to 10 milligrams per day prednisone or equivalent) and received 80mg intramuscular injections of methylprednisolone on days 1 and 15.
Patients achieving a defined reduction in lupus activity were then randomized to receive either intravenous infusions of XmAb5871 or a placebo every two weeks for up to 16 doses.
The trial’s primary endpoint was defined as the percentage of patients with loss of improvement — that is, those whose lupus activity worsened to pre-steroid levels — 225 days after the study’s start.
Xencor announced that treatment with XmAb5871 led to a positive trend in this primary endpoint. At day 225, disease activity was kept low in 42% of the patients treated with XmAb5871, compared to 28.6% of the patients who received the placebo.
Moreover, disease activity took significantly longer to rise in patients taking XmAb5871, a median of 230 days, compared with those on a placebo, who took a median of 131 days.
Those results translated into a 47% reduction in the odds of disease worsening when patients were taking XmAb5871.
The treatment was well-tolerated and the safety profile was consistent with prior studies. The most common adverse events reported in the XmAb5871-treated patients were temporary infusion-related gastrointestinal side effects. There were serious adverse events in seven antibody-treated patients and four placebo patients. No opportunistic infections or deaths were observed.
The results have been selected for a poster presentation at the 2018 American College of Rheumatology (ACR) Annual Meeting on Oct 23. The study is titled “Top-Line Results of a Phase 2, Double-Blind, Randomized, Placebo-Controlled Study of a Reversible B Cell Inhibitor, XmAb®5871, in Systemic Lupus Erythematosus (SLE).”
“Xencor completed this study to efficiently assess the potential of XmAb5871 in SLE, now the third indication where a promising treatment effect has been seen, after rheumatoid arthritis and IgG4-related disease,” Bassil Dahiyat, PhD, president and chief executive officer at Xencor, said in a news release.
“By year end, we plan to initiate a Phase 3 study of XmAb5871 in IgG4-RD, and we are exploring further development in SLE in the context of partnering.”