La Jolla Pharmaceutical (LJP) Company (SAN DIEGO, Calif.) announced that it has reactivated enrollment in its phase III 12-month treatment trial of Riquent® (abetimus sodium) for the treatment of lupus renal disease. To date, the company has activated 30 sites, 21 in the US and 9 in Asia. Additionally, the company is expanding the study to Europe and Mexico. A total of approximately 600 patients from about 100 clinical sites in more than 10 countries will be enrolled in this international study. LJP expects to complete recruitment in the second half of 2007.

Deirdre Y. Gillespie, MD, President/CEO of LJP was quoted as saying, "This global phase III study will be the largest clinical trial ever conducted in lupus patients with a history of renal disease."
   
The current study follows a review of the LJP New Drug Application for Riquent by the Food and Drug Administration (FDA), which informed the Company that Riquent was "approvable," subject to the successful completion of another phase III clinical benefit trial. The current trial, designed under a Special Protocol Assessment (SPA) with the FDA, is a double-blind, placebo-controlled, randomized trial, specifying two doses of Riquent that are higher than those used in previous studies. Previous research indicates that higher Riquent doses may further reduce levels of antibodies to double-stranded DNA (dsDNA), which are believed to cause lupus renal disease, and thus may increase the clinical benefit of treatment with Riquent. Patients with impaired renal function showed increased benefit from Riquent treatment.

Twice as many patients will be treated with Riquent as will be treated with placebo (2:1 randomization). A total of 80% of Riquent-treated patients will be treated with a higher dose than the previous phase III trial: 40% of Riquent-treated patients will receive 300 mg of Riquent per week, 40% will receive 900 mg per week, and 20% will receive 100 mg per week, the dose used in previous trials. 

Riquent has already been evaluated in 13 clinical trials over a 10-year period that evaluated more than 800 subjects. Riquent's only known biologic activity is the reduction of antibodies to dsDNA that are associated with the progression of lupus renal disease and renal flares. In all clinical trials where antibodies to dsDNA were measured, Riquent treatment has significantly reduced these antibody levels. Data generated from the LJP's previous phase II/III and phase III trials indicated that patients with lower antibody levels experienced significantly fewer renal flares and improved health-related quality of life.

LJP is also developing a novel class of compounds, called ToleragensR, with the goal of inactivating targeted B cells in autoimmune disease. Toleragens have been developed with epitopes made from oligonucleotides, peptides, and carbohydrates. LJP has shown in animal models of lupus, antibody-mediated thrombosis, and xenotransplantation that each kind of Toleragen is able to reduce production of the targeted antibodies and the B cells producing them. Based on these studies, LJP believes it can create Toleragens for a number of diseases.

— A. Techman

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