Xencor announced the beginning of two Phase 2 clinical trials testing its drug candidate, XmAb5871, to treat systemic lupus erythematosus (SLE) and IgG4-related disease (IgG4-RD), a rare fibro-inflammatory autoimmune disorder. In both trials, a first patient has already received an initial testing dose.
XmAb5871 is a monoclonal antibody that targets both CD19 and the FcγRIIb receptor, two molecules that exist on the surface of B-cells and whose targeting leads to the inhibition of B-cell function, toning down immune system activity in autoimmune diseases. According to Xencor, XmAb5871 is the first drug candidate that targets FcγRIIb inhibition.
Studies with multiple animal models and initial human trials have demonstrated that the drug is effective in inhibiting B-cell function without destroying these important cells, the company said in a press release. Therapeutic effect was demonstrated in rheumatoid arthritis patients, and data were presented at the American College of Rheumatology’s 2015 annual meeting. Researchers have also demonstrated the drug’s therapeutic potential for SLE in ex vivo experiments, where the compound was shown to inhibit B-cell activation and humoral immunity.
The Phase 2 SLE trial will evaluate XmAb5871’s ability to maintain improvement in disease activity obtained after treatment with intra-muscular (IM) steroid therapy, without immunosuppressant medication. The randomized and placebo-controlled clinical study is taking place across some 20 U.S. sites, and is expected to enroll about 90 people. Participants will discontinue background immunosuppressive medication and receive IM steroids for a short time, to reduce and stabilize disease activity. They then will receive either placebo or XmAb5871 every two weeks, for a total of 12 infusions given over six months, and disease activity will be monitored. The primary endpoint is the drug’s ability to maintain the improved disease activity achieved by IM steroids, while secondary endpoints include the time to loss of SLE disease improvement and assessment of safety and tolerability.
“The SLE trial is designed to assess the effect of XmAb5871 on SLE disease activity with a shorter time to endpoint and with fewer patients compared to standard SLE trials, which generally add new medications to the many medications already taken by the patient,” said Paul Foster, MD, chief medical officer of Xencor.