PDL BioPharma, Inc, of Fremont, California, announced that new data from studies of Nuvion® (visilizumab, a humanized low FcR-binding IgG2 anti-CD3 monoclonal antibody) in Crohn's disease (CD) and ulcerative colitis (UC) were presented at the annual Digestive Disease Week meeting, held May 20–25, 2006, in Los Angeles. In addition to the first presentation of preliminary clinical data evaluating Nuvion in moderate-to-severe inflammatory, nonpenetrating CD, investigators also presented research data that further characterize Nuvion's potential mechanism of action and support the continued investigation of Nuvion in patients with intravenous steroid-refractory UC (IVSR-UC).

An oral presentation titled "A Phase I Study: Visilizumab Therapy in Crohn's Disease (CD) Patients Refractory to Infliximab Treatment" given by Daan Hommes MD, head of the Center for Inflammatory Bowel Diseases at the Academic Medical Center in Amsterdam, reported preliminary results from a multicenter, open-label study of Nuvion in moderate-to-severe, inflammatory, nonpenetrating CD. The data suggested that two 10 mcg/kg doses of Nuvion administered by IV bolus injection on consecutive days appeared to have clinical activity. Ten of the 14 patients reported a clinical response by day 59, as determined by a drop in the Crohn's Disease Activity Index (CDAI) score of 100 points. Five patients achieved a complete remission, as defined by a CDAI score of <e;150 during the 59 days. Of note, two patients who never responded to infliximab, as well as seven patients who lost their response to infliximab, responded to Nuvion.

Three poster presentations by PDL describing research analyses used patient samples from a now-completed phase I/II study of Nuvion in IVSR-UC patients. Of the 76 patients treated with Nuvion and evaluated in an interim analysis, 51 responded to treatment. In one study an increase in peripheral CD8+ T-cell counts and serum IP-10 (interferon-inducible protein 10) levels were observed long after Nuvion was cleared from the circulation and were associated with clinical response to Nuvion in IVSR-UC subjects. These biomarkers could be asso­ciated with durable clinical response to Nuvion. A second study reported that in Nuvion-treated IVSR-UC subjects, clinical response is associated with changes in peripheral and mucosal CD8+ T-cells and Nuvion can induce CD8+ regulatory T cells in vitro. The induction of regulatory CD8+ T-cells may contribute to Nuvion's observed clinical activity. The third presentation reported that the histological evaluation of biopsy samples pre- and post-Nuvion treatment demonstrates a decrease in histological disease activity in the majority of clinical responders. Clinical response to Nuvion also coincides with reduction of mononuclear cell proliferation in the lamina propria (assessed by Ki67 staining); reduction in other inflammatory markers; and a relative increase of CD8+ cells within the remaining CD3+ T-cell population in the colonic mucosa.

PDL is continuing to enroll patients in its pivotal phase II/III RESTORE 1 trial, which is investigating Nuvion as a potential treatment option in IVSR-UC patients. Pending a DSMB (Data Safety Monitoring Board) review later in 2006, PDL hopes to initiate a second pivotal phase III study of Nuvion in UC patients.

—A. Techman