Dose Dependent Reduction in Anti-dsDNA Antibody Levels Observed With Abetimus Sodium Through 52 Weeks in the Phase 3 ASPEN Study (Abetimus Sodium in Patients With a History of Lupus Nephritis)

Michael J. Tansey, Tenshang Joh, Matthew D. Linnik

Background / Purpose: Abetimus sodium (100 mg/wk) has been evaluated in two randomized controlled efficacy trials for ability to prolong time to renal flare in patients with lupus nephritis. While these studies did not reject the null hypothesis for the primary endpoint, they demonstrated that patients who experienced sustained reductions in anti-dsDNA antibody levels had significantly fewer renal flares compared with those whose antibody levels remained at baseline or increased (A&R 2005 52:1129-37). The ongoing phase 3 ASPEN study is evaluating whether higher doses of abetimus prolong time to renal flare compared to placebo. An interim analysis was conducted in this trial to evaluate the effect of abetimus on anti-dsDNA antibodies levels through 52 weeks of treatment.

Methods: Patients were required to have SLE, a history of renal disease and anti-dsDNA ≥ 10 IU/ml (Farr). Patients were randomized to weekly placebo or abetimus 100 mg, 300 mg or 900 mg; randomization to the 100 mg group has been discontinued. Anti-dsDNA levels were measured by Farr assay in the first 125 patients randomized and were analyzed by an independent statistical analysis group. Only group-wise data were reported to the sponsor to preserve the study blind. Clinical efficacy parameters were not assessed in this analysis.

Results: Statistically significant reductions in anti-dsDNA antibody levels were observed when comparing each abetimus treatment arm compared to placebo (p < 0.0001). Anti-dsDNA levels in the placebo group remained at baseline levels throughout the 12 month treatment period. An area under the curve (AUC) analysis, which reflects the effect of the drug on anti-dsDNA levels over time, showed a dose dependent reduction in anti-dsDNA levels across the treatment groups (reduction of 26.9% for 100 mg, 35.5% for 300 mg, 37.7% for 900 mg, compared with an increase of 7.5% for placebo). The proportion of patients achieving a 50% or greater reduction in AUC from baseline was 0.0% in the placebo and 100 mg groups, 23% in the 300 mg group and 30% in the 900 mg group. At time of abstract submission, the Independent Data Monitoring Board (DMB) has completed three reviews of the safety data and has not indicated any safety issues.

Conclusions: In the ongoing Phase 3 ASPEN study, an interim analysis of the anti-dsDNA data indicate that 300 mg and 900 mg doses of abetimus effectively provide significant and sustained reductions in anti-dsDNA antibody levels in patients with lupus nephritis. Antibody levels in the placebo group remained at baseline and the DMB has not communicated any safety concerns to date. The ASPEN study will provide definitive data on the efficacy and safety of abetimus 300 mg/wk and 900 mg/wk in maintenance of remission in patients with lupus nephritis.

Disclosure - Michael J. Tansey, Tenshang Joh and Matthew D. Linnik are all employed by La Jolla Pharmaceutical Company.

American Society of Nephrology
Saturday, November 3, 2007 10:00 AM
Poster Session: Outcomes and Treatments in the Glomerular Diseases (10:00 AM-12:00 PM)
Poster Board Number: SA-PO1019