California-based La Jolla Pharmaceutical Company (Nasdaq: LJPC) has reviewed recently announced safety and interim antibody data related to Riquent (abetimus sodium), its drug candidate for systemic lupus erythematosus (lupus or SLE) at the 8th International Congress on SLE. Its current Phase III study highlighted the definitive and significant dose response observed between the 100 mg, 300 mg and 900 mg doses of Riquent compared with placebo (p=0.0001). The second presentation reviewed the safety and drug levels of Riquent at doses up to 2400 mg in healthy volunteers and the third, cardiovascular safety in healthy volunteers.
”These three presentations provide important, additional data that continue to indicate that Riquent is well tolerated even at much higher doses,” said Deirdre Y. Gillespie, M.D., President and Chief Executive Officer of La Jolla Pharmaceutical Company. “Unlike other medications currently used to treat lupus that can severely suppress the immune system and can result in serious infections, Riquent is highly specific and designed not to suppress the healthy functions of the immune system. We believe that Riquent has the potential to be highly efficacious and well-tolerated – it is designed to specifically target and reduce antibodies to double-stranded DNA (anti-dsDNA) that are believed to cause lupus renal disease.”
Interim Antibody Data
Michael Tansey, M.D., Ph.D., the Company’s Chief Medical Officer, presented a detailed review of the recently announced interim antibody reduction data from the current international Phase III clinical trial of Riquent in a talk entitled: “Effect of Three Doses of Abetimus and Placebo on ds-DNA Antibodies in Patients with SLE and a History of Renal Flare - An Interim Analysis.”
In the talk, Dr. Tansey highlighted data supporting the dose response observed between the 100 mg, 300 mg and 900 mg doses of Riquent compared with placebo (p=0.0001). The reductions in median antibody levels between the Riquent treatment groups and the placebo treatment group at week 8 were 100 mg: 30%; 300 mg: 40%; 900 mg: 58% (p=0.0032, p<0.0001, p<0.0001, respectively). To date, the adverse event profile for all patients in the study, including those treated with the 300 mg and 900 mg doses, does not appear to differ from that seen in previous studies, where only 100 mg of Riquent was the treatment dose.
Riquent Drug Levels and Safety at Higher Doses
In addition to Dr. Tansey’s talk, the company presented two posters detailing data from previously completed clinical safety studies of Riquent. The first poster, “Safety and Pharmacokinetic Assessment of Abetimus Sodium in Healthy Volunteers,” evaluated the safety, tolerability and pharmacokinetics of Riquent at doses up to 2400 mg in healthy male and female volunteers. Riquent was well tolerated at all doses. As seen with many DNA-containing drugs, Riquent treatment was associated with a dose-dependent increase in activated partial thromboplastin time (aPTT), but not prothrombin time (PT), which was not considered clinically significant.
Electrocardiographic Safety
The second poster presentation, “Electrocardiographic Safety Assessment of Abetimus Sodium in Healthy Volunteers,” summarized cardiovascular safety assessments including the potential to increase QT wave prolongation following Riquent treatment at doses of 100 mg and 300 mg. Studies to evaluate the potential of a new drug to increase QT wave prolongation are standard safety assessments of most drugs in development. The data demonstrated no effect of abetimus on changes in QT wave prolongation from baseline. In this study, Riquent was well tolerated and the incidence of adverse events was similar in the placebo, 100 mg and 300 mg groups. In addition, patients exhibited no serious adverse events, and no subject discontinued the study.
About Riquent
Riquent is being developed to specifically treat lupus renal disease by preventing or delaying renal flares, a leading cause of sickness and death in lupus patients. Riquent has been well tolerated in all 13 clinical trials, with no serious Riquent-related side effects identified to date. Riquent’s only known biological activity is the reduction of circulating levels of anti-dsDNA antibodies. Increases in these antibodies are associated with an increased risk of renal flare. Although clinical benefit has not yet been proven, Riquent treatment has significantly reduced these antibody levels in all clinical trials where they were measured.
About Lupus
Lupus is a chronic, potentially life-threatening autoimmune disease. About 90% of lupus patients are female, and many are diagnosed with the disease during their childbearing years. Approximately 50% of lupus patients have renal disease, which can lead to irreversible renal damage, renal failure and the need for dialysis, and is a leading cause of death in lupus patients. 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 U.S.