8 October 2018 - - US-based biopharmaceutical company Xencor, Inc. (NASDAQ: XNCR) has received topline results from the randomized, double-blind, placebo-controlled Phase 2 study of XmAb5871 in patients with systemic lupus erythematosus, the company said.

Patients discontinued background immunosuppressive medication and received a short course of intramuscular steroids to quiet SLE disease activity. Patients achieving the required disease activity improvement (SLEDAI decrease ≥4 points, or ≥1 grade decrease in ≥1 BILAG A or B score) were randomized 1: 1 to receive XmAb5871 (n = 52) or placebo (n = 52) every 14 days for up to 16 doses.

The primary endpoint of the study was the proportion of patients with no loss of improvement (i.e., maintenance of improvement) in the efficacy-evaluable population, defined as those who completed Day 225, had LOI, or discontinued due to a drug-related adverse event.

LOI was defined as a SLEDAI increase ≥4 points or a new BILAG A or B score and physician intent to treat with rescue medication.

In the primary endpoint analysis, improvement was maintained at Day 225 by 42% of patients (21/50) in the XmAb5871-treated arm, compared to 28.6% of patients (12/42) in the placebo-treated arm (p = 0.18).

The efficacy-evaluable population excludes 10/52 placebo patients and 2/52 XmAb5871-treated patients who withdrew from the study for reasons other than LOI or adverse event.

These exclusions led to higher placebo response rates compared to the intent-to-treat population.

In the ITT population, improvement was maintained by 40.4% of patients (21/52) in the XmAb5871-treated arm, compared to 23.1% of patients (12/52) in the placebo-treated arm (p = 0.06).

Secondary endpoints included evaluations of time to LOI and safety and tolerability of XmAb5871. Patients in the efficacy-evaluable population treated with XmAb5871 experienced a statistically significant longer time to LOI (median = 230 days, hazard ratio = 0.53, p = 0.025), compared to placebo-treated patients (median = 131 days), a 76% improvement in median time to LOI and a 47% reduction in risk of LOI.

Safety was consistent with previous trials. The most common adverse events in XmAb5871-treated patients were transient, infusion-related gastrointestinal side effects during the first or second infusion.

There were eight serious AEs in seven XmAb-treated patients and five SAEs in four placebo patients. No opportunistic infections or deaths were reported. The incidence of major organ flares was low (placebo arm:2 nephritis, 1 enteritis, 1 systemic flare; XmAb5871 arm: 1 pneumonitis).

All were treated and stabilized.

XmAb5871 is a first-in-class monoclonal antibody that targets CD19 with its variable domain and uses Xencor's XmAb immune inhibitor Fc domain to target FcγRIIb, a receptor that inhibits B-cell function.

XmAb5871 is the first drug candidate that Xencor is aware of that targets FcγRIIb inhibition. Xencor has demonstrated through multiple preclinical and early-stage clinical studies that XmAb5871 inhibits B-cell function without destroying these important immune cells and has demonstrated a promising treatment effect in rheumatoid arthritis and IgG4-related disease patients.

XmAb5871 is currently in clinical development for IgG4-RD and SLE.

Xencor anticipates initiating a Phase 3 study of XmAb5871 in patients with IgG4-related disease during the second half of 2018.

Xencor is a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases and cancer.