Interim Analysis Reveals Dose Dependent Reduction in Anti-dsDNA Antibody Levels 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, La Jolla Pharmaceutical Company, San Diego, CA

Background / Purpose: Abetimus sodium is a novel therapeutic designed to specifically reduce anti-dsDNA levels. The ongoing phase 3 ASPEN study is evaluating whether abetimus prolongs time to renal flare compared to placebo. An interim analysis was conducted in this trial to evaluate the effect of abetimus on anti-dsDNA antibody 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. Anti-dsDNA levels were assessed in the first 125 patients randomized 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.

Results: Statistically significant reductions in anti-dsDNA antibody levels were observed in each abetimus arm compared to placebo (p < 0.0001). Anti-dsDNA levels in the placebo group remained at baseline levels throughout the 12 month treatment period. A dose dependent reduction in anti-dsDNA levels was observed (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: This interim analysis demonstrates that abetimus provides sustained reductions in anti-dsDNA antibody levels in patients with lupus nephritis. 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 and Tenshang Joh are employed by La Jolla Pharmaceutical Company. Matthew D. Linnik was 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