Xencor, Inc., a biopharmaceutical company that specializes in developing monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases, and cancer recently announced the preliminary results of their Phase 1b/2a Rheumatoid Arthritis study for XmAb5871.
XmAb5871 is a first-in-class monoclonal antibody that targets the CD19 variable domain, and uses an immune inhibitor (XmAb) Fc domain to target the FcγRIIb receptor, resulting in the inhibition of B-cell function. The XmAb5871 study was able to meet its primary safety and tolerability endpoints, and the drug showed encouraging activity in patients with rheumatoid arthritis (RA), including multiple DAS28-CRP remissions and ACR50 and ACR70 responses.
The Phase 2a cohort involved 15 Xmab5871-treated patients and 8 given a placebo who were examined for RA activity after two weeks, following the sixth biweekly infusion. The results revealed 33% of the patients had DAS28-CRP remission or low disease activity compared to zero in the placebo group. Furthermore, 20% of the patients on XmAb5871 had ACR70 responses and 40% had ACR50 responses, compared to zero and 13% in the placebo group, respectively.
The most common adverse effects noted were mild to moderate gastrointestinal toxicities, but these did not occur in the following infusions, and no infusions were discontinued due to any adverse effects. Other adverse effects experienced by the patients that received XmAb5871 were fever, headache, infusion-related reactions, and venous thrombosis.
“XmAb5871’s reduction of RA disease activity demonstrates for the first time that its unique mechanism of action targeting FcγRIIb can be effective at treating an autoimmune disease, and builds on the potent, reversible B-cell inhibition we observed in our Phase 1a clinical trial,” said Paul Foster, M.D., chief medical officer of Xencor. “We have begun translational and mechanistic studies of XmAb5871 in the rare autoimmune disorder IgG4-RD and during 2015 we plan to initiate an open-label pilot clinical trial in IgG4-RD to assess control of disease activity as measured by the IgG4-RD Responder Index (Carruthers, et al., 2012, Int J Rheum).”
“XmAb5871 is our most advanced wholly-owned program and provides us with a number of therapeutic development opportunities where B-cell inhibition shows promise. We are very encouraged by these results, and anticipate a dialogue with the FDA on our clinical development plans in IgG4-RD and other indications,” said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor in a press release.
Xencor is still conducting safety, pharmacokinetics, immunogenicity and efficacy analyses and expects to present their final results in an upcoming conference this year.