DOSE DEPENDENT REDUCTION IN ANTI-dsDNA ANTIBODY LEVELS OBSERVED IN THE ABETIMUS LJP 394-90-14 PHASE 3 TRIAL

Michael J. Tansey, Tenshang Joh, Martthew D. Linnik, Bevra H. Hahn. La Jolla Pharmaceutical Company, La Jolla, CA; UCLA, Los Angeles, CA

INTRODUCTION: In an ongoing Phase 3 randomized controlled trial (RCT), an interim analysis was conducted to assess whether higher doses of abetimus reduce the levels of antibodies to double-stranded DNA (anti-dsDNA) further than 100 mg.

METHODS: We evaluated the reduction in anti-dsDNA as measured by the Farr assay at three central laboratories from the first 101 patients that had received 8 consecutive weekly doses of either abetimus at 100 mg, 300 mg, 900 mg or placebo in the ongoing 90-14 abetimus Phase 3 trial. The analyses were conducted by an independent statistical analysis group and only group-wise data were reported to the sponsor.

RESULTS: Demographics and baseline characteristics were comparable across dosing groups. A significant dose response was observed when comparing all abetimus-treated patients to placebo-treated patients (p < 0.0001). The median percent reductions at week 8 were 100 mg: 18% (n=16); 300 mg: 28% (n=30); 900 mg: 46% (n=26) compared to an increase of 12% (n=29) in the placebo group. At week 8, 73% (900 mg), 70% (300 mg), 50% (100 mg) and 10% (placebo) had at least a 10% reduction from baseline. Approximately three times as many patients treated with 900 mg of abetimus (42%) had at least a 50% or greater antibody reduction at week 8 compared with patients treated with 100 mg (13%). Nearly twice as many patients on 900 mg as 300 mg had a consistent reduction of 50% or greater at weeks 4, 6, and 8 (23% vs 13%). No patients on 100 mg or placebo achieved this level of consistent reduction. The adverse event profile for all patients in the study, including those treated with the 300 mg and 900 mg doses, does not appear to differ from that seen in previous studies where 100 mg per week of abetimus was the treatment dose.

CONCLUSIONS: Data from two previous RCTs demonstrated that patients with sustained reductions in anti-dsDNA antibody levels had significantly fewer renal flares compared with those whose antibody levels remained at baseline or increased (Linnik MD, et al., A&R 2005 52:1129-37). In the current Phase 3 RCT, initial antibody reduction data indicate that the higher the abetimus dose, the greater the percent of patients with consistent reductions and the greater the magnitude of reduction. Separation between dose groups was observed after four weeks of treatment. To date, abetimus has been well tolerated in the ongoing Phase 3 study.

Abstract for
American College of Rheumatology
October 2007
Boston, MA