La Jolla Pharmaceutical Company (SAN DIEGO, Calif.), a biotechnology company developing therapeutics for antibody-mediated autoimmune diseases and inflammation, announced  progress and the expansion of its phase III trial of RiquentR (abetimus sodium, previously referred to as LJP 394) for the treatment of lupus renal disease, a leading cause of sickness and death in patients with lupus. The company now has over 22 clinical sites in the US and at least 36 in Asia, including sites in Hong Kong, India, the Republic of Korea, the Philippines, and Taiwan, with the intent to add sites in other areas, including Europe, Mexico, and possibly South America, to bring the total number of sites to at least 120.
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The clinical trial is a randomized, double-blind, placebo-controlled, four-arm, parallel-group, multi-center, multinational safety and efficacy trial of 100 mg, 300 mg, and 900 mg of Riquent in systemic lupus erythematosus (SLE) patients with a history of renal disease. This phase III study has planned to enroll approximately 600 patients, and most of these patients will be treated with higher doses than in previous studies. This trial will assess a 300 mg per week and a 900 mg per week dose, as well as the 100 mg per week dose used in the prior phase III trial, with a 52-week treatment duration. Of the 600 patients, two-thirds will be treated with Riquent, and the majority of the Riquent-treated patients will receive one of the two higher doses. The primary outcome of the study is to determine whether Riquent is more effective than placebo in delaying the time to renal flare in SLE patients with a history of SLE renal disease. The secondary outcomes are to determine whether treatment with Riquent is more effective than placebo in delaying the time to major SLE flare and if this treatment is more effective than placebo in reducing proteinuria.

Reactivated in August 2006, 99 patients are currently being screened for potential enrollment in the study. The company estimates that only 30% to 50% of the patients in screening should be eligible for study enrollment. The target for completing patient recruitment is the second half of 2007.

Riquent is the first drug candidate specifically developed for the treatment of lupus renal disease. Approximately 50% of lupus patients have renal disease. Although many lupus patients may initially develop mild forms of kidney disease, it often progresses over time to become more severe and can lead to irreversible renal damage, renal failure, and the need for dialysis. Latinos, African Americans, and Asians face an increased risk of serious renal disease associated with lupus. The current standard of care for lupus renal disease often involves treatment with high doses of corticosteroids and immunosuppressive drugs that can cause severe side effects including diabetes, hypertension, and sterility, and may leave patients vulnerable to opportunistic infections. To date, no lupus specific drug has been approved in the US.

Riquent has already been evaluated in 13 clinical trials over a 10-year time span that evaluated more than 800 patients and subjects. Riquent has been well tolerated in all of these studies, with no serious side effects identified to date. Riquent's only known biological activity is the reduction of antibodies to double-stranded DNA (dsDNA), produced by diseased B-cells, that are associated with the progression of lupus renal disease and renal flares. These antibodies are believed to cause lupus kidney disease that can lead to kidney failure, dialysis, kidney transplantation, and death.

In all clinical trials where antibodies to dsDNA were measured, Riquent treatment has significantly reduced these antibody levels. Data generated from the company'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.

The US FDA has granted La Jolla Pharmaceutical orphan drug designation for Riquent for the treatment of lupus kidney disease. The Orphan Drug Act provides for 7 years of marketing exclusivity in the US and enables the company to obtain research funding, tax credits for certain research expenses, and a waiver of the application user fees.

—A. Techman