Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases and cancer, today announced dosing the first patient in a Phase 2 trial of XmAb®5871 in patients with IgG4-Related Disease (IgG4-RD). The Company also announced dosing the first patient in a Phase 2 trial of XmAb5871 in patients with Systemic Lupus Erythematosus (SLE).
"We are advancing XmAb5871 in IgG4-RD and SLE because of its potent, reversible B-cell inhibition and promising treatment effect demonstrated in a Phase 1b/2a study of patients with rheumatoid arthritis, as well as previous ex vivo results with XmAb5871 showing inhibition of SLE patient B-cell activation and humoral immunity," said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor. "B-cell inhibition by XmAb5871 has potential in a number of autoimmune diseases, and we believe we can execute efficient clinical trials with clear outcomes in these indications and potentially address high unmet needs. In IgG4-RD, a newly defined disease, we have the opportunity to be at the forefront of providing a treatment for patients."
The Phase 2 pilot study in IgG4-RD is an open-label single-arm trial being conducted at Massachusetts General Hospital by Dr. John H. Stone. Approximately 15 patients with active IgG4-RD will receive intravenous (IV) administrations of XmAb5871 every 2 weeks for 6 months. The primary objective of the study is to evaluate the effect of every other week IV administration of XmAb5871 on the IgG4-RD Responder Index (RI) in patients with active IgG4-RD. Secondary and exploratory objectives are to determine the safety and tolerability profile, to characterize the pharmacokinetics and pharmacodynamics (change in biomarkers) and to characterize immunogenicity of every other week IV administration of XmAb5871 in patients with active IgG4-RD.
The Phase 2 SLE trial is a novel design to evaluate the ability of XmAb5871 to maintain the improvement in disease activity after a short course of intra-muscular (IM) steroid therapy and in the absence of immunosuppressant medication. This trial design was previously tested in an observational study by Dr. Joan T. Merrill of the Oklahoma Medical Research Foundation, who is the coordinating investigator for the XmAb5871 SLE trial. When background treatments are reduced, six month response rates to a brief course of steroids are known to be low without the addition of an effective therapy.
"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, M.D., chief medical officer of Xencor.
The Phase 2 study in SLE is a randomized, double-blind, placebo-controlled, multiple dose trial being conducted in the US at approximately 20 sites. Approximately 90 SLE patients will be enrolled with a 1:1 randomization of XmAb5871 to placebo. Patients will enter screening with active, non-organ threatening SLE. They will discontinue background immunosuppressive medication and receive a short course of IM steroids to quiet SLE disease activity. Patients who achieve the required disease activity improvement will be randomized to receive XmAb5871 or placebo every two weeks for up to 12 infusions (six months) and will be followed for loss of disease improvement. The primary objective of the study is to evaluate the ability of XmAb5871 to maintain SLE disease activity improvement achieved by a brief course of disease-suppressing IM steroid therapy. Secondary and exploratory objectives are to evaluate the time to loss of SLE disease activity improvement, to determine the safety and tolerability profile, to characterize the pharmacokinetics and pharmacodynamics (change in biomarkers), and to characterize immunogenicity of every other week IV administration of XmAb5871 in patients with SLE.
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