REDUCTIONS IN ANTIBODIES TO DOUBLE-STRANDED DNA IN LUPUS PATIENTS TREATED WITH ABETIMUS SODIUM IN INTERNATIONAL PHASE 3 STUDY

Michael Tansey, MD, PhD, Matthew D. Linnik, PhD, Tenshang Joh, PhD, Andrew Wiseman, PhD, LJP 394-90-14 International Investigator Consortium La Jolla Pharmaceutical Company, San Diego, CA, USA

Abstract

Purpose. Abetimus sodium (LJP 394; abetimus) is being evaluated in an international Phase 3 clinical study to compare doses of 100, 300 and 900 mg per week to placebo to determine if drug treatment will increase time to renal flare in SLE patients with a history of renal disease. An interim analysis is planned to assess the pharmacodynamic dose response by measuring reductions in antibodies to double-stranded DNA (anti-dsDNA) following 8 weeks of treatment.

Methods. An ongoing international, double-blind, randomized, placebo-controlled study (RCT) is designed to enroll approximately 700 patients with elevated anti-dsDNA (>10 IU by Farr assay) and a history of lupus renal disease. A serology interim analysis performed by an independent statistical analysis center will evaluate the pharmacodynamic response to treatment. Approximately 130 patients who complete 8 weeks of treatment are to be included in the analysis. Summary demographics and baseline characteristics including disease activity, renal function parameters, and prednisone dose will be reported for each treatment group. Pharmacodynamic assessments measured weekly include mean, median, range of reduction in anti-dsDNA per group, as well as a repeated measures analysis comparing all treatment groups to placebo. Dose response will be assessed by comparing the least squares mean for each group to placebo at various time points. Patients with at least a 10%, 20%, 30%, 40% or 50% reduction from baseline at weeks 4 and 8 will be summarized.

Results. Previous studies have demonstrated that abetimus treatment results in a dose-dependent reduction in anti-dsDNA antibodies levels in SLE patients over a dose range from 10mg to 100mg per week. The current pharmacodynamic interim analysis will evaluate the effect of abetimus on anti-dsDNA antibody levels at doses of 100mg, 300mg and 900mg per week.

Conclusion. The results from this serology interim analysis will indicate if doses of abetimus higher than 100mg per week will further reduce anti-dsDNA after 8 weeks of treatment. Previously reported analyses have demonstrated a relationship between reduction in anti-dsDNA antibody levels and reduction in risk of renal flare in SLE patients with a history of renal disease.

Presented at the
The 8th International Congress on SLE
Shanghai, China
May 23-27, 2007