From the Archives: Fall 2006 Issue of Lupus Now Magazine
Drug Spotlight: Update on Abetimus Sodium (Riquent®)
Riquent was specifically developed for the treatment of lupus kidney disease, a leading cause of serious illness for people with lupus. The drug candidate has already been studied over a 10-year time span in 13 clinical trials that evaluated the drug's effect on more than 800 people with lupus and healthy subjects. Riquent was found to be well tolerated in all of these studies, with no serious side effects identified to date. Riquent is being developed by La Jolla Pharmaceutical Company (LJPC) in San Diego, CA.
How Riquent Might Help Lupus Kidney Disease
Riquent is a highly specialized treatment developed to target specific antibodies associated with kidney disease (called antibodies to double-stranded DNA, or anti-dsDNA) that are found in people with lupus. Some of these antibodies sit on the surface of a B cell-a white blood cell that is integral to the inflammation that causes lupus. Riquent has the potential to link these surface antibodies together (cross-linking) and send a signal into the B cell that might cause its death. However, it is not known if this is actually what happens when the drug is given to people. What is known for sure is that Riquent lowers the levels of similar antibodies that are circulating in the bloodstream.
Furthermore, since Riquent only targets those antibodies that are associated with kidney disease, and might only kill the specific B cells that express those antibodies (leaving all other B cells and all other natural antibodies intact), this treatment has the potential to be much safer than drugs that suppress more of the immune system's usual functions.
Current therapies for lupus kidney disease-such as high doses of steroids and chemotherapy drugs-have increased the survival of people with lupus kidney disease. However, the percentage of patients who still go on to lose their kidneys and the toxic effects of these drugs are unacceptable to patients and their doctors, who are waiting for safer and more effective treatments to be fully studied. There is high interest in finding out whether Riquent could be effective, since it seems to be so well tolerated and since, at least in theory, it has the potential to block or delay lupus kidney disease without suppressing the healthy functions of the immune system.
Recruitment Under Way for New Riquent Study
A clinical trial to determine if Riquent can prevent kidney flares is currently enrolling participants. Entitled "A Randomized, Double-blind, Placebo-controlled, Four-arm, Parallel-group, Multicenter, Multinational Safety and Efficacy Trial of 100 mg, 300 mg, and 900 mg of Abetimus Sodium in Systemic Lupus Erythematosus (SLE) Patients with a History of Renal Disease," the trial's primary outcome is to determine whether Riquent, given weekly in a 52-week time period, is more effective than placebo (a "dummy" treatment with no potential benefits) in delaying the time to kidney flare in lupus patients with a history of lupus renal disease. Another question to be studied is whether treatment with Riquent is more effective than placebo in delaying the time to a major lupus flare of any kind, whether it is in the kidneys or not.
Riquent Trial Overview
The protocol of the new clinical trial includes several modifications that are designed to improve the probability of demonstrating the clinical benefit of Riquent. The changes to the protocol incorporated in the current study are based on data generated during La Jolla Pharmaceutical's previous Phase II/III and Phase III trials of Riquent. These changes include the following.
Twice as many patients will be treated with Riquent as will be treated with placebo (a 2:1 randomization), meaning 80 percent of Riquent-treated patients will be treated with a higher dose than the previous Phase III trial. Forty percent will receive 300 mg of Riquent per week, 40 percent will receive 900 mg per week, and 20 percent will receive 100 mg per week (the dose used in the previous trials). Because of the positive safety profile of the drug candidate, studying the effects of increased dosage was encouraged by the Food and Drug Administration, which oversees all clinical trials in the U.S. Company officials believe that higher doses of Riquent should further reduce levels of antibodies to dsDNA, which may increase the clinical benefit of treatment with the lupus drug candidate.
Approximately 600 patients will be enrolled in this new trial, compared with approximately 300 patients in the previous Phase III study. Studying a larger number of patients should increase the likelihood of seeing a statistically significant difference between the Riquent-treated group and the placebo-treated group.
The primary endpoint of the study, time to renal flare, has been simplified by eliminating hematuria (blood in the urine) from the definition of a renal flare. Hematuria can occur due to conditions other than a renal flare, and can be a less specific test result for lupus kidney disease.
The current trial will evaluate the treatment for 12 months, as compared with the previous Phase III trial, which treated study participants for up to 22 months.
The study entry criteria will further restrict the use of immunosuppressive agents. In the previous Phase III study, the use of these agents may have reduced the renal flare rate, especially in placebo-treated individuals.
The trial will involve a greater number of nephrology clinics, which should allow the study to enroll more people with impaired kidney function; it is that specific group that showed increased benefit from Riquent treatment.
Participating in the Trial
Currently there are 21 active study sites in the United States and nine in Asia. La Jolla Pharmaceutical is expanding the study to Europe and Mexico, and eventually about 100 clinical sites in more than 10 countries will take part. The clinical trial for Riquent will need a total of 600 participants who have a history of lupus kidney disease. To find out how to qualify for the trial, or for more information about the study, go to clinicaltrials.gov and search "Riquent."