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

Michael P. Madaio, Tenshang J. Joh, Matthew D. Linnik, Michael J. Tansey, La Jolla Pharmaceutical Company, La Jolla, CA; Nephrology and Kidney Transplantation, Temple University School of Medicine, Philadelphia, PA

INTRODUCTION: In an ongoing Phase 3 RCT, interim analysis was conducted to assess whether higher doses of abetimus, further than 100 mg, reduce anti-dsDNA levels

METHODS: Reduction in anti-dsDNA (Farr) was measured at 3 central laboratories from 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. Analyses were conducted by an independent statistical 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 12% increase in the placebo group (n=29). At week 8, 73% (900 mg), 70% (300 mg), 50% (100 mg) and 10% (placebo) had ≥ 10% reduction from baseline. Approximately 3X as many patients treated with 900 mg of abetimus (42%) had ≥ 50% antibody reduction at week 8 compared with 100 mg treated patients (13%). Nearly 2X 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 differ from previous studies using 100 mg/week of abetimus.

CONCLUSIONS: Higher abetimus dose resulted in greater % patients with consistent reductions, and greater magnitude reduction in anti-dsDNA. Separation between dose groups was observed after 4 weeks, and drug was well tolerated. Since two previous RCTs demonstrated that patients with sustained reductions in anti-dsDNA antibody levels had significantly fewer renal flares (Linnik MD, et al., A&R 2005 52:1129-37), it will be important to determine whether increased dose is beneficial.

Disclosure - Major Stock Shareholder: 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