La Jolla Pharmaceutical Co (SAN DIEGO, California) announced positive 12-month interim antibody data from its ongoing double-blind, placebo-controlled, randomized phase III ASPEN study of Riquent^® (abetimus sodium) for systemic lupus erythematosus (SLE). Analyses of data in the first 125 randomized patients indicate that for all patients treated with weekly 900 mg, 300 mg, or 100 mg of Riquent compared with placebo, there were significantly greater reductions in antibodies to double-stranded (ds) DNA (P <.0001).

The drug is being developed to specifically treat lupus renal disease by preventing or delaying renal flares, a leading cause of sickness and death in SLE patients. Antibodies to dsDNA are implicated as a primary cause of lupus renal disease, and decreases in these antibodies are believed to be associated with a reduction in the risk of renal flare. Antibody levels were measured every 2 weeks for the first 16 weeks and then monthly for the remaining 36 weeks. All demographics and baseline characteristics were comparable across dosing groups.

Although clinical benefit has not yet been proven, Riquent treatment has significantly reduced dsDNA antibody levels in all clinical trials in which the levels were measured. The drug is also being studied to assess whether it improves proteinuria, as was observed in previous clinical trials.

Equal numbers of patients are being treated with 300 mg per week, 900 mg per week, or placebo. A small number of patients are receiving 100 mg per week. All patients continue to receive standard of care which can include background immunosuppressive therapies. The data show a dose-response curve for antibody reduction and also show that the 300 mg and 900 mg doses appear to be near the top of the antibody-related dose-response curve. Antibody levels in the placebo-treated group remained around baseline levels throughout the 12 months. The rate at which antibody levels were maximally reduced appeared to be more rapid in the 900 mg dose group than in the 300 mg or 100 mg dose groups.

Each dose group was significantly different from placebo (P <.0001). An area under the curve (AUC) analysis, which reflects the effect of the drug on antibody levels over time, showed significantly greater antibody-lowering effects for the 300 mg and 900 mg dose groups compared with the placebo group (decreases of 26.9% for 100 mg, 35.5% for 300 mg, and 37.7% for 900 mg, compared with an increase of 7.5% for placebo). The proportion of patients achieving ≥50% AUC reduction was 0% in the placebo and 100 mg groups, 23% in the 300 mg group, and 30% in the 900 mg group.

More than 670 patients at >140 clinical sites have been enrolled in the study. Compliance with weekly visits has been high and the drop-out rate remains low. The Independent Data Monitoring Board (DMB) has completed three reviews of the safety data and has not indicated any safety issues. The trial is expected to be completed in the second half of 2009. The first interim efficacy analysis is expected in the fourth quarter of 2008, and the second interim efficacy analysis is expected midway between the first analysis and the expected study’s end.

Riquent has received an approval letter and fast track status from the US FDA, and has orphan drug designation in the US and Europe. To date, no SLE-specific drug has been approved in the US.