Xoma and Servier’s mAb Fails to Reduce HbA1C Levels in Phase IIb Type 2 Diabetes Study

Xoma and partner Servier’s interleukin-1β monoclonal antibody Xoma 052 failed to reduce HbA1c levels in type 2 diabetes patients, according to Phase IIb trial data. The drug did, however, significantly reduce levels of C-reactive protein (CRP) and increased levels of HDL, which supports its potential use in cardiovascular disease and other inflammatory conditions, the firm claims. Xoma separately plans to start Phase III development of Xoma 052 in the treatment of Behcet’s uveitis, later this year. A Phase II study in patients with Behcet’s uveitis has already been successfully completed.

Meanwhile, Xoma and Servier are waiting on the completion of another Phase IIa diabetes study and will analyze both sets of trial data before deciding on the future development of Xoma 052 for this indication.

The reported U.S.-based Phase IIb diabetes study trial enrolled 421 patients with type 2 disease who were receiving metformin monotherapy. Participants were randomized to receive either placebo, or one of four doses of Xoma 052 administered monthly over six months. While patients in the investigational antibody cohorts showed no improvements in HbA1c levels compared with those receiving placebo, all Xoma 052 cohorts demonstrated reductions in CRP at six months, and two of the four Xoma 052 groups demonstrated significant increases in HDL. About half the patients were already receiving lipid-lowering medications, Xoma points out.

“The potent anti-inflammatory effects and continued positive safety profile reinforce our Phase III development program of Behcet’s uveitis,” notes Steven B. Engle, Xoma’s chairman and CEO. “We also expect to take Xoma 052 into clinical development in cardiovascular disease in 2012,” adds Isabelle Tupinon-Mathieu, M.D., Servier’s head of therapeutic R&D.

Under terms of Xoma and Servier’s joint development and commercialization collaboration for Xoma 052, the latter has global rights to the antibody for the diabetes and cardiovascular disease indications, and global rights excluding Japan and the U.S. for other indications. Xoma retains commercial rights and options in the U.S. and Japan for multiple potential indications including Behcet’s uveitis and other inflammatory and oncology indications. Servier is also providing the first $50 million in development costs for Xoma 052 against the  Behcet’s uvitis indication, and 50% of the remaining costs for this indication. The firm is responsible for funding development of the antibody for the cardiovascular disease and diabetes indications. Xoma will manufacture the antibody at least through clinical development and launch, and probably over the long term, it notes.